3-[tert-butyl(diphenyl)silyl]oxycyclobutan-1-one

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1.0 M potassium tert-butoxide in tetrahydrofuran (46.0 mL, 46.0 mmol) at 0° C. was added diethyl cyanomethylphosphonate (7.8 mL, 48 mmol). The bath was removed and the reaction mixture was allowed to warm to room temperature over 1 hour. The reaction was re-cooled to 0° C., and a solution of 3-{[tert-butyl(diphenyl)silyl]oxy}cyclobutanone (15.7 g, 48.4 mmol, from Step 3) in tetrahydrofuran (80 mL) was added. During the course of the addition, additional tetrahydrofuran (50 mL) was added into the receiving flask to facilitate stirring. Upon complete addition of the ketone, the bath was removed and the reaction allowed to reach room temperature and stirred overnight. The reaction mixture was partitioned between water and ethyl acetate and the aqueous was extracted with ethyl acetate a total of three times. The combined extracts were washed with brine, dried over sodium sulfate, decanted and concentrated. Flash chromatography, eluting with a gradient of 0-10% ethyl acetate in hexanes afforded product (16.1 g, 96%). 1H NMR (300 MHz, CDCl3): δ 7.74-7.58 (m, 4H), 7.49-7.34 (m, 6H), 5.13 (dddd, 1H), 4.34 (tt, 1H), 3.16-2.90 (m, 4H), 1.05 (s, 9H). The bath was removed The reaction was re-cooled to 0° C. was added into the receiving flask the bath was removed to reach room temperature stirred overnight The reaction mixture was partitioned between water and ethyl acetate the aqueous was extracted with ethyl acetate a total of three times The combined extracts were washed with brine dried over sodium sulfate decanted concentrated Flash chromatography, eluting with a gradient of 0-10% ethyl acetate in hexanes afforded product (16.1 g, 96%)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1.0 M potassium tert-butoxide in tetrahydrofuran (46.0 mL, 46.0 mmol) at 0° C. was added diethyl cyanomethylphosphonate (7.8 mL, 48 mmol). The bath was removed and the reaction mixture was allowed to warm to room temperature over 1 hour. The reaction was re-cooled to 0° C., and a solution of 3-{[tert-butyl(diphenyl)silyl]oxy}cyclobutanone (15.7 g, 48.4 mmol, from Step 3) in tetrahydrofuran (80 mL) was added. During the course of the addition, additional tetrahydrofuran (50 mL) was added into the receiving flask to facilitate stirring. Upon complete addition of the ketone, the bath was removed and the reaction allowed to reach room temperature and stirred overnight. The reaction mixture was partitioned between water and ethyl acetate and the aqueous was extracted with ethyl acetate a total of three times. The combined extracts were washed with brine, dried over sodium sulfate, decanted and concentrated. Flash chromatography, eluting with a gradient of 0-10% ethyl acetate in hexanes afforded product (16.1 g, 96%). 1H NMR (300 MHz, CDCl3): δ 7.74-7.58 (m, 4H), 7.49-7.34 (m, 6H), 5.13 (dddd, 1H), 4.34 (tt, 1H), 3.16-2.90 (m, 4H), 1.05 (s, 9H). The bath was removed The reaction was re-cooled to 0° C. was added into the receiving flask the bath was removed to reach room temperature stirred overnight The reaction mixture was partitioned between water and ethyl acetate the aqueous was extracted with ethyl acetate a total of three times The combined extracts were washed with brine dried over sodium sulfate decanted concentrated Flash chromatography, eluting with a gradient of 0-10% ethyl acetate in hexanes afforded product (16.1 g, 96%)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of tert-butyl {[3-(methylsulfinyl)-3-(methylthio)cyclobutyl]oxy}diphenylsilane (17.05 g, 40.7 mmol, from Step 2) in ether (350 mL) cooled to 0° C. was treated with a solution of 6 M perchloric acid in water (10 mL) that was pre-diluted with water (7 mL). The bath was removed and stirred overnight. The mixture was poured into pH 7 buffer, and the product was extracted with diethyl ether. The combined extracts were dried over sodium sulfate, decanted and concentrated. The reaction was performed again on the same scale and the two batches were combined for purification. Flash chromatography, eluting with a gradient from 0-5% ethyl acetate/hexanes afforded desired product (15.7 g, 59%). 1H NMR (300 MHz, CDCl3): δ 7.75-7.62 (m, 4H), 7.49-7.33 (m, 6H), 4.59 (tt, 1H), 3.22-3.03 (m, 4H), 1.07 (s, 9H). The bath was removed The mixture was poured into pH 7 buffer the product was extracted with diethyl ether The combined extracts were dried over sodium sulfate decanted concentrated the two batches were combined for purification Flash chromatography, eluting with a gradient from 0-5% ethyl acetate/hexanes

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 1.0 M of potassium tert-butoxide in tetrahydrofuran (1.2 mL) was added dropwise, at 0° C., diethyl cyanomethylphosphonate (0.19 mL, 0.0012 mol). The reaction was warmed to rt and 30 min later cooled to 0° C. again. To the reaction mixture was added a solution of 3-[tert-butyl(diphenyl)silyl]oxycyclobutanone (0.25 g, 0.00077 mol) in THF (5 mL). The reaction was allowed to warm up to rt gradually and stirred at rt for 2 h. The reaction was quenched with saturated aq. NH4Cl, extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, concentrated. The resultant residue was purified with Combiflash (silica gel, 0-20% EtOAc/Hex) to give the desired product (0.2 g) as colorless oil. LCMS calculated for C22H26NOSi(M+H)+: 348.1 Found: 348.3. later cooled to 0° C. again to warm up to rt gradually The reaction was quenched with saturated aq. NH4Cl extracted with EtOAc The combined organic layers were washed with brine dried over MgSO4 concentrated The resultant residue was purified with Combiflash (silica gel, 0-20% EtOAc/Hex)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 1.0 M of potassium tert-butoxide in tetrahydrofuran (1.2 mL) was added dropwise, at 0° C., diethyl cyanomethylphosphonate (0.19 mL, 0.0012 mol). The reaction was warmed to rt and 30 min later cooled to 0° C. again. To the reaction mixture was added a solution of 3-[tert-butyl(diphenyl)silyl]oxycyclobutanone (0.25 g, 0.00077 mol) in THF (5 mL). The reaction was allowed to warm up to rt gradually and stirred at rt for 2 h. The reaction was quenched with saturated aq. NH4Cl, extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, concentrated. The resultant residue was purified with Combiflash (silica gel, 0-20% EtOAc/Hex) to give the desired product (0.2 g) as colorless oil. LCMS calculated for C22H26NOSi(M+H)+: 348.1 Found: 348.3. later cooled to 0° C. again to warm up to rt gradually The reaction was quenched with saturated aq. NH4Cl extracted with EtOAc The combined organic layers were washed with brine dried over MgSO4 concentrated The resultant residue was purified with Combiflash (silica gel, 0-20% EtOAc/Hex)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1.0M potassium tert-butoxide in tetrahydrofuran (5.95 mL, 5.95 mmol) at 0° C. was added diethyl cyanomethylphosphonate (1.05 g, 5.95 mmol). The bath was removed and reaction allowed to warm to room temperature for 1 hour. The reaction was cooled to 0° C. and a solution of 3-{[tert-butyl(diphenyl)silyl]oxy}cyclobutanone (1.95 g, 6.01 mmol) in THF (10 mL) was added. Upon complete addition, the bath was removed and the reaction was allowed to warm to room temperature and stir overnight. The reaction solution was diluted with water and ethyl acetate. The aqueous layer was extracted with ethyl acetate three times. The combined extracts were washed with brine, dried over sodium sulfate, decanted and concentrated. The crude was purified silica gel column to give the desired product (2.07 g, 90%) as an oil. LCMS (M+H)+: 348.2. The bath was removed reaction The reaction was cooled to 0° C. Upon complete addition the bath was removed to warm to room temperature The reaction solution was diluted with water and ethyl acetate The aqueous layer was extracted with ethyl acetate three times The combined extracts were washed with brine dried over sodium sulfate decanted concentrated The crude was purified silica gel column

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1.0M potassium tert-butoxide in tetrahydrofuran (46.0 mL, 46.0 mmol) at 0° C. was added diethyl cyanomethylphosphonate (7.8 mL, 48 mmol). The bath was removed and the reaction mixture was allowed to warm to room temperature over 1 hour. The reaction was re-cooled to 0° C., and a solution of 3-{[tert-butyl(diphenyl)silyl]oxy}cyclobutanone (15.7 g, 48.4 mmol, from Step 3) in tetrahydrofuran (80 mL) was added. During the course of the addition, additional tetrahydrofuran (50 mL) was added into the receiving flask to facilitate stirring. Upon complete addition of the ketone, the bath was removed and the reaction allowed to reach room temperature and stirred overnight. The reaction mixture was partitioned between water and ethyl acetate and the aqueous was extracted with ethyl acetate a total of three times. The combined extracts were washed with brine, dried over sodium sulfate, decanted and concentrated. Flash chromatography, eluting with a gradient of 0-10% ethyl acetate in hexanes afforded product (16.1 g, 96%). 1H NMR (300 MHz, CDCl3): δ 7.74-7.58 (m, 4H), 7.49-7.34 (m, 6H), 5.13 (dddd, 1H), 4.34 (tt, 1H), 3.16-2.90 (m, 4H), 1.05 (s, 9H). The bath was removed The reaction was re-cooled to 0° C. was added into the receiving flask the bath was removed to reach room temperature stirred overnight The reaction mixture was partitioned between water and ethyl acetate the aqueous was extracted with ethyl acetate a total of three times The combined extracts were washed with brine dried over sodium sulfate decanted concentrated Flash chromatography, eluting with a gradient of 0-10% ethyl acetate in hexanes afforded product (16.1 g, 96%)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of tert-butyl{[3-(methylsulfinyl)-3-(methylthio)cyclobutyl]oxy}diphenylsilane (17.05 g, 40.7 mmol, from Step 2) in ether (350 mL) cooled to 0° C. was treated with a solution of 6M perchloric acid in water (10 mL) that was pre-diluted with water (7 mL). The bath was removed and stirred overnight. The mixture was poured into pH 7 buffer, and the product was extracted with diethyl ether. The combined extracts were dried over sodium sulfate, decanted and concentrated. The reaction was performed again on the same scale and the two batches were combined for purification. Flash chromatography, eluting with a gradient from 0-5% ethyl acetate/hexanes afforded desired product (15.7 g, 59%). 1H NMR (300 MHz, CDCl3): δ 7.75-7.62 (m, 4H), 7.49-7.33 (m, 6H), 4.59 (tt, 1H), 3.22-3.03 (m, 4H), 1.07 (s, 9H). The bath was removed The mixture was poured into pH 7 buffer the product was extracted with diethyl ether The combined extracts were dried over sodium sulfate decanted concentrated the two batches were combined for purification Flash chromatography, eluting with a gradient from 0-5% ethyl acetate/hexanes

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1.0 M potassium tert-butoxide in tetrahydrofuran (46.0 mL, 46.0 mmol) at 0° C. was added diethyl cyanomethylphosphonate (7.8 mL, 48 mmol). The bath was removed and the reaction mixture was allowed to warm to room temperature over 1 hour. The reaction was re-cooled to 0° C., and a solution of 3-{[tert-butyl(diphenyl)silyl]oxy}cyclobutanone (15.7 g, 48.4 mmol, from Step 3) in tetrahydrofuran (80 mL) was added. During the course of the addition, additional tetrahydrofuran (50 mL) was added into the receiving flask to facilitate stirring. Upon complete addition of the ketone, the bath was removed and the reaction allowed to reach room temperature and stirred overnight. The reaction mixture was partitioned between water and ethyl acetate and the aqueous was extracted with ethyl acetate a total of three times. The combined extracts were washed with brine, dried over sodium sulfate, decanted and concentrated. Flash chromatography, eluting with a gradient of 0-10% ethyl acetate in hexanes afforded product (16.1 g, 96%). 1H NMR (300 MHz, CDCl3): δ 7.74-7.58 (m, 4H), 7.49-7.34 (m, 6H), 5.13 (dddd, 1H), 4.34 (tt, 1H), 3.16-2.90 (m, 4H), 1.05 (s, 9H). The bath was removed The reaction was re-cooled to 0° C. was added into the receiving flask the bath was removed to reach room temperature stirred overnight The reaction mixture was partitioned between water and ethyl acetate the aqueous was extracted with ethyl acetate a total of three times The combined extracts were washed with brine dried over sodium sulfate decanted concentrated Flash chromatography, eluting with a gradient of 0-10% ethyl acetate in hexanes afforded product (16.1 g, 96%)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of tert-butyl {[3-(methylsulfinyl)-3-(methylthio)cyclobutyl]oxy}diphenylsilane (17.05 g, 40.7 mmol, from Step 2) in ether (350 mL) cooled to 0° C. was treated with a solution of 6 M perchloric acid in water (10 mL) that was pre-diluted with water (7 mL). The bath was removed and stirred overnight. The mixture was poured into pH 7 buffer, and the product was extracted with diethyl ether. The combined extracts were dried over sodium sulfate, decanted and concentrated. The reaction was performed again on the same scale and the two batches were combined for purification. Flash chromatography, eluting with a gradient from 0-5% ethyl acetate/hexanes afforded desired product (15.7 g, 59%). 1H NMR (300 MHz, CDCl3): δ 7.75-7.62 (m, 4H), 7.49-7.33 (m, 6H), 4.59 (tt, 1H), 3.22-3.03 (m, 4H), 1.07 (s, 9H). The bath was removed The mixture was poured into pH 7 buffer the product was extracted with diethyl ether The combined extracts were dried over sodium sulfate decanted concentrated the two batches were combined for purification Flash chromatography, eluting with a gradient from 0-5% ethyl acetate/hexanes