反应 #1702103

反应方程式

ethyl acetate dichloromethane

(1S,6S)-4,6-Dimethyl-cyclohex-3-ene-carboxylic acid [5-(3,3-dimethyl-but-1-ynyl)-thiophen-3-yl]-(trans-4-hydroxy-cyclohexyl)-amide

lithium diisopropylamine

→

title compound

5-(3,3-Dimethyl-but-1-ynyl)-3-[(1S,6S)-(4,6-dimethyl-cyclohex-3-enecarbonyl)-(4-hydroxy-cyclohexyl)-amino]-thiophene-2-carboxylic acid

溶剂

THF

反应条件

后处理

1. 1
   其他CO2 was vigorously bubbled through the reaction solution for 10 minutes
2. 2
   其他The reaction was then quenched with the addition of iPrOH
3. 3
   workup.ADDITIONdiluted with ethyl acetate
4. 4
   洗涤washed with saturated NH4Cl(aq)
5. 5
   干燥dried over MgSO4
6. 6
   过滤filtered
7. 7
   浓缩concentrated

实验过程

(1S,6S)-4,6-Dimethyl-cyclohex-3-ene-carboxylic acid [5-(3,3-dimethyl-but-1-ynyl)-thiophen-3-yl]-(trans-4-hydroxy-cyclohexyl)-amide (1.74 g, 4.2 mmol) in THF (50 mL) was cooled to −78° C. and treated with lithium diisopropylamine (8.4 mL, 2.0M in heptane/THF/PhEt, 16.8 mmol) and allowed to warm to 0° C. over the course of 2 hours. CO2 was vigorously bubbled through the reaction solution for 10 minutes. The reaction was then quenched with the addition of iPrOH, diluted with ethyl acetate, washed with saturated NH4Cl(aq), dried over MgSO4, filtered, and concentrated. Silica gel chromatography (0-100% ethyl acetate/dichloromethane) afforded 530 mg (1.2 mmol) of the title compound: MS (m/z): 458.1 [M+H]+; HPLC retention time 4.35 min (2-98% acetonitrile: water with 0.05% trifluoroacetic acid).

来源