methyl (2S)-3-hydroxy-2-methylpropanoate

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

実験手順: A solution of (S)-(+)-methyl 3-hydroxy-2-methylpropionate (1.18 g, 10 mmol) in t-butyl acetate (30 mL) was treated with 70% HClO4 (0.1 mL) and the reaction mixture was left at room temperature in a tightly closed flask for 24 hours. The mixture was then poured into a saturated solution of NaHCO3 and extracted with ethyl ether. The ether was removed in vacuo and the residue was dissolved in THF (50 mL). To the resulting solution was added NaBH4 (925 mg, 25 mmol) and at 55° C. dropwise methanol (10 mL). The reaction was continued at 55° C. for 1 hours, then it was cooled to ambient temperature, acidified with 10% citric acid to pH 5 and extracted with ethyl acetate. The acetate extract was washed with water, brine, dried with MgSO4 and concentrated in vacuo. The residue was chromatographed (silica gel, 2:1 hexane-ethyl acetate) to provide (R)-3-t-butoxy-2-methyl-1-propanol (yield: 1 g, 68%). 1H NMR (300 MHz, CDCl3) δ 0.85 (d, J=7 Hz, 3H), 1.20 (s, 9H), 2.03 (m, 1H), 3.30 (t, J=12 Hz, 1H), 3.53 (dd, J=4.5 Hz, 12 Hz, 1H), 3.70 (m, 2H); MS (DCI/NH3) m/z 164 (M+NH4)+. extracted with ethyl ether The ether was removed in vacuo the residue was dissolved in THF (50 mL) at 55° C. The reaction was continued at 55° C. for 1 hours extracted with ethyl acetate The acetate extract was washed with water, brine dried with MgSO4 concentrated in vacuo The residue was chromatographed (silica gel, 2:1 hexane-ethyl acetate)

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

実験手順: To a stirred solution of 2-fluoro-4-hydroxybenzonitrile (1.0 g, 7.3 mmol), (S)-3-hydroxy-2-methyl-propionic acid methyl ester (0.8 mL, 7.3 mmol) and triphenylphosphine (2.3 g, 8.8 mmol) at room temperature, diethyl azodicarboxylate (1.4 mL, 8.8 mmol) was added dropwise. The mixture was stirred at room temperature overnight, diluted with ethyl acetate and washed successively with dilute aqueous sodium hydroxide, dilute aqueous hydrochloric acid, brine, and dried (MgSO4). Solvents were stripped in vacuo. The resulting oil was washed with diethyl ether and the precipitate was filtered off. The mother liquor was adsorbed onto silica gel and the product purified by flash column chromatography (40% ethyl acetate/hexane), affording 0.14 g of a yellow oil (8% yield). washed successively with dilute aqueous sodium hydroxide, dilute aqueous hydrochloric acid, brine dried (MgSO4) The resulting oil was washed with diethyl ether the precipitate was filtered off the product purified by flash column chromatography (40% ethyl acetate/hexane)

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

実験手順: A mixture of methyl (S)-(+)-3-hydroxy-2-methylpropionate (1.00 g; 8.47 mmol) and imidazole (1.15 g; 16.9 mmol) was dissolved in anhydrous dimethylformamide (10 ml), and t-butyl-dimethylchlorosilane (1.30 g; 8.62 mmol) was added thereto at room temperature, followed by stirring at room temperature for 1.5 hours. To the reaction mixture, water (10 ml) and hexane (20 ml) were added, and after separation of the organic layer, the aqueous layer was extracted with hexane (10 ml) two times. The organic layers were combined together, washed with water (5 ml) three times and dried over anhydrous magnesium sulfate. Removal of the solvent by distillation under reduced pressure gave methyl (S)-(+)-3-(t-butyldimethylsilyloxy)-2-methylpropionate (1.91 g; yield, 97%) as a colorless oil. A portion of the oil (179 mg) was distilled by Kugelrohr® to give a purified product (176 mg) (bath temperature: 120° C./14 mmHg). at room temperature after separation of the organic layer the aqueous layer was extracted with hexane (10 ml) two times washed with water (5 ml) three times dried over anhydrous magnesium sulfate Removal of the solvent by distillation under reduced pressure

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

実験手順: A mixture of 5.9 g (0.05 mole) of (S)-(+)methyl 3-hydroxy-2-methylpropionate, 9.5 g (0.055 mole) of phenyl sulfamate, 25 ml of toluene and 0.5 g of pyridine was heated at reflux for 2 hr. The reaction solution was concentrated under vacuum, and the residue was chromatographed, using silica gel and eluting with 2% methanol in methylene chloride. The desired fractions were concentrated under vacuum to give 3.9 g (40%) of a pale yellow oil. was heated at reflux for 2 hr The reaction solution was concentrated under vacuum the residue was chromatographed eluting with 2% methanol in methylene chloride The desired fractions were concentrated under vacuum

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

実験手順: A solution of methyl 3-hydroxy-2-(S)-methylpropanoate (35 g, 295 mmol) in 830 mL of CH2Cl2, under N2 atmosphere, was cooled to -60° C. With rapid stirring, methanesulfonyl chloride (24 mL, 310 mmol) was added, followed by Et3N (50 mL, 354 mmol) over 90 s. As the addition ended, a heavy white precipitate formed which stopped the magnetic stirring. The cold bath was removed and the reaction allowed to reach r.t. The reaction mixture was poured into aq 25% NH4OAc. After separation, the organic phase was dried over MgSO4 and evaporated to give the title compound as a colorless oil (59.1 g, 102%). As the addition a heavy white precipitate formed which The cold bath was removed to reach r.t The reaction mixture was poured into aq 25% NH4OAc After separation the organic phase was dried over MgSO4 evaporated

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

実験手順: A solution of methyl 3-hydroxy-2-(S)-methylpropanoate (35 g, 295 mmol) in 830 mL of CH2Cl2, under N2 atmosphere, was cooled to -60° C. With rapid stirring, methanesulfonyl chloride (24 mL, 310 mmol) was added, followed by Et3N (50 mL, 354 mmol) over 90 s. As the addition ended, a heavy white precipitate formed which stopped the magnetic stirring. The cold bath was removed and the reaction allowed to reach r.t. The reaction mixture was poured into aq 25% NH4OAc. After separation, the organic phase was dried over MgSO4 and evaporated to give the title compound as a colorless oil (59.1 g, 102%). As the addition a heavy white precipitate formed which The cold bath was removed to reach r.t The reaction mixture was poured into aq 25% NH4OAc After separation the organic phase was dried over MgSO4 evaporated

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

実験手順: A mixture of (S)-(+)-methyl-3-hydroxy-2-methylpropionate (10.0 g), 2,3-dihydropyran (10.0 g) and D,L-10-camphorsulfonic acid in CH2Cl2 (200 ml) was stirred for 30 min at room temperature. The reaction was quenched by the addition of saturated aqueous NaHCO3, followed by extraction with ether. The combined extracts were washed with water, dried over MgSO4 and concentrated to give 17.1 g of crude product. A solution of crude product (17.1 g) in ether (30 ml) was added dropwise during 40 min to a stirred and ice cooled suspension of LiAlH4 (3.21 g) in dry ether (300 ml). The stirring was continued for 30 min at room temperature. The excess LiAlH4 was decomposed by the successive addition of water (8 ml), 15% NaOH (8 ml) and water (24 ml) and the stirred and ice-cooled mixture was filtered. The filtrate was dried over MgSO4 and concentrated in vacuo. The residue was distilled to give 14.6 g of (1). b.p. 85 89/3.5 mmHg. The reaction was quenched by the addition of saturated aqueous NaHCO3 followed by extraction with ether The combined extracts were washed with water dried over MgSO4 concentrated to give 17.1 g of crude product a stirred ice cooled The stirring was continued for 30 min at room temperature the stirred ice-cooled mixture was filtered The filtrate was dried over MgSO4 concentrated in vacuo The residue was distilled

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

実験手順: A mixture of (S)-(+)-methyl-3-hydroxy-2-methylpropionate (10.0 g), 2,3-dihydropyran (10.0 g) and D,L-10-camphorsulfonic acid in CH2Cl2 (200 ml) was stirred for 30 min at room temperature. The reaction was quenched by the addition of saturated aqueous NaHCO3, followed by extraction with ether. The combined extracts were washed with water, dried over MgSO4 and concentrated to give 17.1 g of crude product. A solution of crude product (17.1 g) in ether (30 ml) was added dropwise during 40 min to a stirred and ice cooled suspension of LiAlH4 (3.21 g) in dry ether (300 ml). The stirring was continued for 30 min at room temperature. The excess LiAlH4 was decomposed by the successive addition of water (8 ml), 15% NaOH (8 ml) and water (24 ml) and the stirred and ice-cooled mixture was filtered. The filtrate was dried over MgSO4 and concentrated in vacuo. The residue was distilled to give 14.6 g of (1). b.p. 85 89/3.5 mmHg. The reaction was quenched by the addition of saturated aqueous NaHCO3 followed by extraction with ether The combined extracts were washed with water dried over MgSO4 concentrated to give 17.1 g of crude product a stirred ice cooled The stirring was continued for 30 min at room temperature the stirred ice-cooled mixture was filtered The filtrate was dried over MgSO4 concentrated in vacuo The residue was distilled

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

実験手順: A solution of (S)-(+)-methyl 3-hydroxy-2-methylpropionate (1.18 g, 10 mmol) in t-butyl acetate (30 mL) was treated with 70% HClO4 (0.1 mL) and the reaction mixture was left at room temperature in a tightly closed flask for 24 hours. The mixture was then poured into a saturated solution of NaHCO3 and extracted with ethyl ether. The ether was removed in vacuo and the residue was dissolved in THF (50 mL). To the resulting solution was added NaBH4 (925 mg, 25 mmol) and at 55° C. dropwise methanol (10 mL). The reaction was continued at 55° C. for 1 hours, then it Was cooled to ambient temperature, acidified with 10% citric acid to pH 5 and extracted with ethyl acetate. The acetate extract was washed with water, brine, dried with MgSO4 and concentrated in vacuo. The residue was chromato graphed (silica gel, 2:1 hexane-ethyl acetate) to provide (R)-3-t-butoxy-2-methyl-1-propanol (yield: 1 g, 68%). 1H NMR (300 Mz, CDCl3) δ 0.85 (d, J=7 Hz, 3H), 1.20 (s, 9H), 2.03 , (m, 1H), 3.30 (t, J=12 Hz, 1H), 3.53 (dd, J=4.5 Hz, 12 Hz, 1H), 3.70 (m, 2H); MS (DCI/N3) m/z 164 (M+NH4)+. extracted with ethyl ether The ether was removed in vacuo the residue was dissolved in THF (50 mL) at 55° C. The reaction was continued at 55° C. for 1 hours extracted with ethyl acetate The acetate extract was washed with water, brine dried with MgSO4 concentrated in vacuo

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

実験手順: A solution of (S)-(+)-methyl 3-hydroxy-2-methylpropionate (1.18 g, 10 mmol) in t-butyl acetate (30 mL) was treated with 70% HClO4 (0.1 mL) and the reaction mixture was left at room temperature in a tightly closed flask for 24 hours. The mixture was then poured into a saturated solution of NaHCO3 and extracted with ethyl ether. The ether was removed in vacuo and the residue was dissolved in THF (50 mL). To the resulting solution was added NaBH4 (925 mg, 25 mmol) and at 55° C. dropwise methanol (10 mL). The reaction was continued at 55° C. for 1 hours, then it Was cooled to ambient temperature, acidified with 10% citric acid to pH 5 and extracted with ethyl acetate. The acetate extract was washed with water, brine, dried with MgSO4 and concentrated in vacuo. The residue was chromato graphed (silica gel, 2:1 hexane-ethyl acetate) to provide (R)-3-t-butoxy-2-methyl-1-propanol (yield: 1 g, 68%). 1H NMR (300 Mz, CDCl3) δ 0.85 (d, J=7 Hz, 3H), 1.20 (s, 9H), 2.03 , (m, 1H), 3.30 (t, J=12 Hz, 1H), 3.53 (dd, J=4.5 Hz, 12 Hz, 1H), 3.70 (m, 2H); MS (DCI/N3) m/z 164 (M+NH4)+. extracted with ethyl ether The ether was removed in vacuo the residue was dissolved in THF (50 mL) at 55° C. The reaction was continued at 55° C. for 1 hours extracted with ethyl acetate The acetate extract was washed with water, brine dried with MgSO4 concentrated in vacuo

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

実験手順: Methyl (S)-(+)-2-methyl-3-hydroxypropionate (1.0 g; 8.47 mmole) and imidazole (1.15 g; 16.9 mmole) were dissolved in dry dimethylfofmamide (10 ml), t-butyl dimethylchlorosilane (1.30 g; 8.62 mmole) was added thereto, and the resultant mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate (60 ml), washed with an aqueous sodium chloride solution (50 ml) three times and dried over anhydrous magnesium sulfate. After removal of the solvent, the residue was purified by silica gel column chromatography to give methyl (S)-3-t-butyldimethylsilyloxy-2-methylpropionate was added washed with an aqueous sodium chloride solution (50 ml) three times dried over anhydrous magnesium sulfate After removal of the solvent the residue was purified by silica gel column chromatography

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

実験手順: Methyl (S)-(+)-2-methyl-3-hydroxypropionate (1.18 g; 10 mmole), trityl chloride (3.1 g; 11.13 mmole) and N,N-dimethylaminopyridine (1.34 g; 11 mmole) were dissolved in dry dimethylformamide (10 ml), and the resultant mixture was stirred at room temperature overnight. Methanol (5 ml) was added thereto to decompose the unreacted trityl chloride, and the resultant mixture was stirred for 3 hours. Water (20 ml) was added to the reaction mixture, which was extracted with toluene (20 ml) three times. The extracts were combined together, washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give methyl (S)-3-trityloxy-2-methylpropionate. was extracted with toluene (20 ml) three times washed with water dried over anhydrous sodium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography