(2S)-1-methoxypropan-2-ol

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

実験手順: Prepared as described in Example 140, Step A, using 8-fluoro-2-methylquinolin-7-ol (0.30 g, 1.69 mmol) in place of 2-methylquinolin-8-ol and using (S)-1-methoxypropan-2-ol (0.196 g, 46%). Prepared

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

実験手順: To a solution of 6-fluoro-2-methylquinolin-8-ol (0.50 g, 2.8 mmol) in tetrahydrofuran (2.4 mL, 2.8 mmol) was added triphenylphosphine (2.6 g, 9.9 mmol), diisopropyl azodicarboxylate (0.91 mg, 4.5 mmol), and (S)-1-methoxypropan-2-ol (0.33 mg, 3.7 mmol) and the resultant mixture allowed to stir at ambient temperature for 24 hours. The reaction mixture was diluted with water (10 mL) and extracted with dichloromethane (2×20 mL). The combined organic extracts dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by normal phase chromatography on silica gel (0-2% methanol/dichloromethane) afforded the title compound which was taken on to the subsequent step without further purification, assuming theoretical yield (0.70 g, 100%) was obtained, despite being contaminated with residual triphenylphosphine oxide. extracted with dichloromethane (2×20 mL) The combined organic extracts dried over sodium sulfate filtered concentrated under reduced pressure Purification by normal phase chromatography on silica gel (0-2% methanol/dichloromethane)

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

実験手順: To a solution of 2-methylquinolin-7-ol (0.20 g, 1.3 mmol) in tetrahydrofuran (1.1 mL, 1.3 mmol) was added triphenylphosphine (0.82 g, 3.1 mmol), diethyl azodicarboxylate (0.32 mL, 2.0 mmol), and (S)-1-methoxypropan-2-ol (0.16 mL, 1.6 mmol) and the resultant mixture allowed to stir at ambient temperature for 24 hours. The reaction mixture was diluted with water (10 mL) and extracted with dichloromethane (2×20 mL). The combined organic extracts dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by reverse phase chromatography on C18 (0-80% acetonitrile/water) afforded the title compound (0.22 g, 66%). extracted with dichloromethane (2×20 mL) The combined organic extracts dried over sodium sulfate filtered concentrated under reduced pressure Purification by reverse phase chromatography on C18 (0-80% acetonitrile/water)

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

実験手順: To a solution of 2-methylquinolin-8-ol (1.0 g, 6.3 mmol) in tetrahydrofuran (5.2 mL, 6.3 mmol) was added triphenylphosphine (6.9 g, 26 mmol), diethyl azodicarboxylate (1.6 mL, 10 mmol), and (S)-1-methoxypropan-2-ol (0.80 mL, 8.2 mmol) and the resultant mixture allowed to stir at ambient temperature for 24 hours. The reaction mixture was diluted with water (10 mL) and extracted with dichloromethane (2×20 mL). The combined organic extracts dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the residue by reverse phase chromatography on C18 (0-80% acetonitrile/water) afforded the title compound (0.46 g, 28%). extracted with dichloromethane (2×20 mL) The combined organic extracts dried over sodium sulfate filtered concentrated under reduced pressure Purification of the residue by reverse phase chromatography on C18 (0-80% acetonitrile/water)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Magnesium perchlorate (2.79 g, 12.49 mmol) was added in one portion to (S)-methyl oxirane-2-carboxylate (CAS no. 118712-39-3) (5.1 g, 49.96 mmol) and (S)-1-methoxypropan-2-ol (CAS no. 26550-55-0) (4.50 g, 49.96 mmol) at ambient temperature. The resulting suspension was stirred at 50° C. for 16 hours. The reaction mixture was diluted with DMF (50 mL) before adding 1H-imidazole (6.80 g, 99.92 mmol) and tert-butylchlorodimethylsilane (9.04 g, 59.95 mmol). The resulting solution was stirred at 40° C. for 5 hours. The reaction mixture was evaporated to dryness and re-dissolved in ethyl acetate (125 mL), and washed sequentially with water (50 mL) and saturated brine (25 mL). The organic layer was dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, eluting with 0 to 50% ethyl acetate in isohexane to afford the product (4.52 g, 30%). 1H NMR (400 MHz, DMSO) δ 0.00 (d, 6H), 0.82 (s, 9H), 0.98 (d, 3H), 3.13-3.28 (m, 5H), 3.50-3.64 (m, 6H), 4.26-4.32 (m, 1H); m/z (ESI+) (M+H)+=307.19; HPLC tR=10.82 min. at ambient temperature The resulting solution was stirred at 40° C. for 5 hours The reaction mixture was evaporated to dryness re-dissolved in ethyl acetate (125 mL) washed sequentially with water (50 mL) and saturated brine (25 mL) The organic layer was dried (MgSO4) evaporated The crude product was purified by flash silica chromatography eluting with 0 to 50% ethyl acetate in isohexane

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Magnesium perchlorate (2.79 g, 12.49 mmol) was added in one portion to (S)-methyl oxirane-2-carboxylate (CAS no. 118712-39-3) (5.1 g, 49.96 mmol) and (S)-1-methoxypropan-2-ol (CAS no. 26550-55-0) (4.50 g, 49.96 mmol) at ambient temperature. The resulting suspension was stirred at 50° C. for 16 hours. The reaction mixture was diluted with DMF (50 mL) before adding 1H-imidazole (6.80 g, 99.92 mmol) and tert-butylchlorodimethylsilane (9.04 g, 59.95 mmol). The resulting solution was stirred at 40° C. for 5 hours. The reaction mixture was evaporated to dryness and re-dissolved in ethyl acetate (125 mL), and washed sequentially with water (50 mL) and saturated brine (25 mL). The organic layer was dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, eluting with 0 to 50% ethyl acetate in isohexane to afford the product (4.52 g, 30%). 1H NMR (400 MHz, DMSO) δ 0.00 (d, 6H), 0.82 (s, 9H), 0.98 (d, 3H), 3.13-3.28 (m, 5H), 3.50-3.64 (m, 6H), 4.26-4.32 (m, 1H); m/z (ESI+) (M+H)+=307.19; HPLC tR=10.82 min. at ambient temperature The resulting solution was stirred at 40° C. for 5 hours The reaction mixture was evaporated to dryness re-dissolved in ethyl acetate (125 mL) washed sequentially with water (50 mL) and saturated brine (25 mL) The organic layer was dried (MgSO4) evaporated The crude product was purified by flash silica chromatography eluting with 0 to 50% ethyl acetate in isohexane

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: DIAD (4.6 g, 0.029 mol) was added dropwise to a solution of methyl 3-hydroxy-5-{[phenylmethyl]oxy}benzoate (6 g, 0.023 mol), (S)-(+)-1-methoxy-2-propanol (2.59 g, 0.029 mol) and triphenylphosphine (7.53 g, 0.029 mol) in THF (100 mL), under argon, at 0° C. The reaction was stirred at 0° C. for 1 hour and at RT for 20 hours. The volatiles were removed in vacuo and isohexane/ethyl acetate 2:1 added followed by stirring for 1 hour. A white solid was removed by filtration and the filtrate was evaporated to a residue which was chromatographed on silica, eluting with a gradient of 0-20% ethyl acetate in isohexane, to give the desired compound (5.11 g). The volatiles were removed in vacuo and isohexane/ethyl acetate 2:1 added by stirring for 1 hour A white solid was removed by filtration the filtrate was evaporated to a residue which was chromatographed on silica eluting with a gradient of 0-20% ethyl acetate in isohexane

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

実験手順: Prepared as described in Example 140, Step A, using 8-fluoro-2-methylquinolin-7-ol (0.30 g, 1.69 mmol) in place of 2-methylquinolin-8-ol and using (S)-1-methoxypropan-2-ol (0.196 g, 46%). Prepared

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

実験手順: To a solution of 6-fluoro-2-methylquinolin-8-ol (0.50 g, 2.8 mmol) in tetrahydrofuran (2.4 mL, 2.8 mmol) was added triphenylphosphine (2.6 g, 9.9 mmol), diisopropyl azodicarboxylate (0.91 mg, 4.5 mmol), and (S)-1-methoxypropan-2-ol (0.33 mg, 3.7 mmol) and the resultant mixture allowed to stir at ambient temperature for 24 hours. The reaction mixture was diluted with water (10 mL) and extracted with dichloromethane (2×20 mL). The combined organic extracts dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by normal phase chromatography on silica gel (0-2% methanol/dichloromethane) afforded the title compound which was taken on to the subsequent step without further purification, assuming theoretical yield (0.70 g, 100%) was obtained, despite being contaminated with residual triphenylphosphine oxide. extracted with dichloromethane (2×20 mL) The combined organic extracts dried over sodium sulfate filtered concentrated under reduced pressure Purification by normal phase chromatography on silica gel (0-2% methanol/dichloromethane)

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

実験手順: To a solution of 2-methylquinolin-7-ol (0.20 g, 1.3 mmol) in tetrahydrofuran (1.1 mL, 1.3 mmol) was added triphenylphosphine (0.82 g, 3.1 mmol), diethyl azodicarboxylate (0.32 mL, 2.0 mmol), and (S)-1-methoxypropan-2-ol (0.16 mL, 1.6 mmol) and the resultant mixture allowed to stir at ambient temperature for 24 hours. The reaction mixture was diluted with water (10 mL) and extracted with dichloromethane (2×20 mL). The combined organic extracts dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by reverse phase chromatography on C18 (0-80% acetonitrile/water) afforded the title compound (0.22 g, 66%). extracted with dichloromethane (2×20 mL) The combined organic extracts dried over sodium sulfate filtered concentrated under reduced pressure Purification by reverse phase chromatography on C18 (0-80% acetonitrile/water)

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

実験手順: To a solution of 2-methylquinolin-7-ol (0.20 g, 1.3 mmol) in tetrahydrofuran (1.1 mL, 1.3 mmol) was added triphenylphosphine (0.82 g, 3.1 mmol), diethyl azodicarboxylate (0.32 mL, 2.0 mmol), and (S)-1-methoxypropan-2-ol (0.16 mL, 1.6 mmol) and the resultant mixture allowed to stir at ambient temperature for 24 hours. The reaction mixture was diluted with water (10 mL) and extracted with dichloromethane (2×20 mL). The combined organic extracts dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by reverse phase chromatography on C18 (0-80% acetonitrile/water) afforded the title compound (0.22 g, 66%). extracted with dichloromethane (2×20 mL) The combined organic extracts dried over sodium sulfate filtered concentrated under reduced pressure Purification by reverse phase chromatography on C18 (0-80% acetonitrile/water)

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

実験手順: To a solution of 2-methylquinolin-8-ol (1.0 g, 6.3 mmol) in tetrahydrofuran (5.2 mL, 6.3 mmol) was added triphenylphosphine (6.9 g, 26 mmol), diethyl azodicarboxylate (1.6 mL, 10 mmol), and (S)-1-methoxypropan-2-ol (0.80 mL, 8.2 mmol) and the resultant mixture allowed to stir at ambient temperature for 24 hours. The reaction mixture was diluted with water (10 mL) and extracted with dichloromethane (2×20 mL). The combined organic extracts dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the residue by reverse phase chromatography on C18 (0-80% acetonitrile/water) afforded the title compound (0.46 g, 28%). extracted with dichloromethane (2×20 mL) The combined organic extracts dried over sodium sulfate filtered concentrated under reduced pressure Purification of the residue by reverse phase chromatography on C18 (0-80% acetonitrile/water)