反应详情

温度

0 °C

(S)-2-(tert-Butoxycarbonylamino)-4,4-dimethylpentanoic acid (50 mg, 0.204 mmol) and iodomethane (0.102 mL, 1.631 mmol) were dissolved in tetrahydrofuran (2 mL) at 0° C. and sodium hydride (24.46 mg, 0.611 mmol) was added. The reaction was stirred at 0° C. for a half hour and at room temperature overnight. The reaction was cooled to 0° C. and ethyl acetate (1 mL) was added followed by dropwise quenching with water (2 mL). The solvent was removed in vacuo and the crude material was partitioned between ether and water. The ether layer was separated. The aqueous layer was acidified to pH-5 using 1 N citric acid and extracted with ethyl acetate. The organic layer was washed with 1 N sodium thiosulfate and brine, dried (Na2SO4) and concentrated in vacuo. The compound was purified using a 4 g silica gel cartridge with a gradient of 0-3% methanol/dichloromethane over 20 minutes to give (S)-2-(tert-butoxycarbonyl(methyl)amino)-4,4-dimethylpentanoic acid: 1H NMR (300 MHz, DMSO-d6) δ ppm 12.63 (s, 1H), 4.57 (ddd, J=74.4, 9.5, 3.1, 1H), 2.69 (s, 3H), 1.83-1.53 (m, 2H), 1.39 (s, 9H), 0.89 (s, 9H); MS (DSI+) m/z 260 (M+H)+.

1. temperatureThe reaction was cooled to 0° C.
2. customby dropwise quenching with water (2 mL)
3. customThe solvent was removed in vacuo
4. customthe crude material was partitioned between ether and water
5. customThe ether layer was separated
6. extractionextracted with ethyl acetate
7. washThe organic layer was washed with 1 N sodium thiosulfate and brine
8. dry with materialdried (Na2SO4)
9. concentrationconcentrated in vacuo
10. customThe compound was purified
11. customover 20 minutes