Reacción #1702103

Ecuación de reacción

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

Disolventes

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroCO2 was vigorously bubbled through the reaction solution for 10 minutes
2. 2
   OtroThe reaction was then quenched with the addition of iPrOH
3. 3
   workup.ADDITIONdiluted with ethyl acetate
4. 4
   Lavadowashed with saturated NH4Cl(aq)
5. 5
   Secadodried over MgSO4
6. 6
   Filtraciónfiltered
7. 7
   Concentraciónconcentrated

Procedimiento

(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).

Fuente