反应详情

温度

-40 °C

A solution of the 2-(tert-butoxycarbonylamino)-2-(ethoxycarbonyl)hex-5-enoic acid (7.5 g, 24.9 mmol) and triethylamine (3.01 g, 29.9 mmol, 4.15 mL) in THF (10 mL) was cooled to −40° C. and treated with ethyl chloroformate (2.97 g, 27.4 mmol, 2.65 mL). After stirring for 30 minutes, the precipitate (triethylamine hydrochloride) was removed by filtration and the filtrate was collected and cooled to −40° C. A solution of sodiumborohydride (950 mg, 24.9 mmol) in water (10 mL) was added and the resulting solution was stirred for 30 minutes. After quenching the reaction mixture with 3 N hydrochloric acid (5 mL), the mixture was diluted with ethyl acetate (150 mL), washed with water (1×50 mL) and extracted with ethyl acetate (1×150 mL). The combined organic layers were concentrated, dried over MgSO4, filtered and purified using a combiflash system (80 g silica gel column, eluting with 10-50% ethyl acetate in heptanes) to give ethyl 2-(tert-butoxycarbonylamino)-2-(hydroxymethyl)hex-5-enoate (5.6 g, 78%). 1H NMR (CDCl3) δ 5.71-5.62 (m, 1H), 5.52 (bs, 1H), 4.96-4.87 (m, 2H), 4.20-4.12 (m, 2H) 4.07-4.03 (m, 2H), 3.73 (d, J=12.0 Hz, 1H), 2.22-1.62 (m, 4H), 1.37 (m, 9H), 1.22 (t, J=7.2 Hz, 3H).

1. customthe precipitate (triethylamine hydrochloride) was removed by filtration
2. customthe filtrate was collected
3. stirringthe resulting solution was stirred for 30 minutes
4. customAfter quenching the reaction mixture with 3 N hydrochloric acid (5 mL)
5. additionthe mixture was diluted with ethyl acetate (150 mL)
6. washwashed with water (1×50 mL)
7. extractionextracted with ethyl acetate (1×150 mL)
8. concentrationThe combined organic layers were concentrated
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. custompurified
12. washa combiflash system (80 g silica gel column, eluting with 10-50% ethyl acetate in heptanes)