Reaction #1702103

Reaction equation

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

Solvents

THF

Conditions

Workup

1. 1
   OtherCO2 was vigorously bubbled through the reaction solution for 10 minutes
2. 2
   OtherThe reaction was then quenched with the addition of iPrOH
3. 3
   workup.ADDITIONdiluted with ethyl acetate
4. 4
   Washwashed with saturated NH4Cl(aq)
5. 5
   Dryingdried over MgSO4
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated

Procedure

(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).

Source