反应详情

温度

0 °C

(2R,3S)-3-(3,4-Dimethoxyphenylsulfanyl)-2-methyl-7-phenylheptanoic acid (0.46 g, 1.2 mmol) is dissolved in CH2Cl2 (4.5 mL) and cooled to 0° C. and to this is added 2 M oxalyl chloride in CH2Cl2 (1.9 mL, 3.8 mmol) over 5 minutes. The ice bath is removed and the reaction allowed to warm to room temperature. After 1.5 hours, the reaction is concentrated in vacuo and azeotroped with chloroform several times. The crude residue is dissolved in CH2Cl2 (4 mL) and O-trimethylsilylhydroxylamine (0.4 g, 3.6 mmol) is added slowly. After 5 minutes, the reaction is diluted with CH2Cl2 (20 mL) and washed with 2 N HCl (15 mL). The aqueous layer is back-extracted with CH2Cl2 (10 mL) and the combined organic layers are washed with water (50 mL), dried over MgSO4 and concentrated in vacuo. The crude residue is azeotroped with ether/petroleum ether and triturated with a large volume of petroleum ether to give (+)-(2R,3S)-3-(3,4-dimethoxyphenylsulfanyl)-2-methyl-7-phenylheptanoic acid hydroxyamide (0.45 g, 94%): [a]D23 +22° (c=1.0, CHCl3); 1H NMR (300 MHz, CD3OD) δ 7.25-7.21 (m, 2H), 7.15-7.10 (m, 3H), 7.05-6.98 (m, 2H), 6.87 (d, J=8.2 Hz, 1H), 3.81 (s, 3H), 3.80 (s, 3H), 3.17-3.14 (m,1H), 2.58-2.52 (m, 2H), 2.35-2.30 (m, 1H), 1.75-1.65 (m, 1H), 1.60-1.40 (m, 5H), 1.17 (d, J=7.0 Hz, 3H); MS (ion spray) m/e 404 (M+H)+ ; Anal. (C22H29NO4S) C, H, N.

1. customThe ice bath is removed
2. temperatureto warm to room temperature
3. concentrationthe reaction is concentrated in vacuo
4. customazeotroped with chloroform several times
5. dissolutionThe crude residue is dissolved in CH2Cl2 (4 mL)
6. waitAfter 5 minutes
7. washwashed with 2 N HCl (15 mL)
8. extractionThe aqueous layer is back-extracted with CH2Cl2 (10 mL)
9. washthe combined organic layers are washed with water (50 mL)
10. dry with materialdried over MgSO4
11. concentrationconcentrated in vacuo
12. customThe crude residue is azeotroped with ether/petroleum ether
13. customtriturated with a large volume of petroleum ether