反应 #161910

反应方程式

triethylamine

#11

(2R,3R)-3-[(2S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl]-3-methoxy-2-methylpropanoic acid

#15

(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethanamine, hydrochloride salt

diethylphosphoryl cyanide

→

#16

收率 81.1%

tert-butyl (2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}propyl]pyrrolidine-1-carboxylate

收率 81.1%

溶剂

N,N-dimethylformamide

ethyl acetate toluene

反应条件

后处理

1. 1
   洗涤was washed successively with 1 M aqueous sodium bisulfate solution (35 mL) and 50% saturated aqueous sodium bicarbonate solution (4×25 mL)
2. 2
   干燥The organic layer was dried over sodium sulfate
3. 3
   过滤filtered
4. 4
   浓缩concentrated in vacuo
5. 5
   其他purified by silica gel chromatography (12% to 100% ethyl acetate in heptane)

实验过程

To a solution of #11 (280 mg, 0.974 mmol, 1 eq.) and #15 (460 mg, 1.44 mmol, 1.48 eq.) in N,N-dimethylformamide (3 mL, 0.32 M) at 0° C. was added diethylphosphoryl cyanide (DEPC) (93% purity, 212 μL, 1.30 mmol, 1.34 eq.), followed by triethylamine (367 μL, 2.63 mmol, 2.7 eq.). After 2 hours at 0° C., the reaction mixture was warmed to room temperature for 18 hours. The reaction mixture was then diluted with ethyl acetate:toluene (2:1, 30 mL) and was washed successively with 1 M aqueous sodium bisulfate solution (35 mL) and 50% saturated aqueous sodium bicarbonate solution (4×25 mL). The organic layer was dried over sodium sulfate, filtered, concentrated in vacuo, and purified by silica gel chromatography (12% to 100% ethyl acetate in heptane) to give #16 as a light amber oil (374 mg, 81%). LC-MS: m/z 474.4 [M+H+], 374.4 [(M−2-methylprop-1-ene)+H+] retention time=3.63 minutes; 1H NMR (400 MHz, DMSO-d6), characteristic signals: δ 8.66 (d, J=8.5 Hz, 1H), 7.78 (d, J=3.3 Hz, 1H), 7.64 (d, J=3.3 Hz, 1H), 7.21-7.31 (m, 4H), 7.14-7.20 (m, 1H), 5.40 (ddd, J=11.4, 8.5, 4.0 Hz, 1H), 3.23 (br s, 3H), 2.18 (dq, J=9.7, 6.7 Hz, 1H), 1.06 (d, J=6.6 Hz, 3H).

来源