Reacción #67575

Ecuación de reacción

3-[(4-amino-cyclohexyl)-(trans-4-methylcyclohexanecarbonyl)-amino]-5-(3,3-dimethyl-but-1ynyl)thiophene-2-carboxylic acid methyl ester

carbonic acid hexahydro-furo[2,3-b]furan-3-yl ester 4-nitro-phenyl ester

DIEA

→

5-(3,3-Dimethyl-but-ynyl)-3-[[4-(hexahydro-furo[2,3-b]furan-3-yloxycarbonylamino)-cyclohexyl]-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester

Disolventes

ACN

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe solvent was removed under reduced pressure
2. 2
   Otrothe crude reaction mixture
3. 3
   Otrowas partitioned between EtOAc and 2N K2CO3(aq)
4. 4
   OtroThe layers were separated
5. 5
   Lavadothe organics washed repeatedly with 2N K2CO3(aq)

Procedimiento

A solution of 3-[(4-amino-cyclohexyl)-(trans-4-methylcyclohexanecarbonyl)-amino]-5-(3,3-dimethyl-but-1ynyl)thiophene-2-carboxylic acid methyl ester (0.40 g, 0.873 mmol) in ACN (5.0 mL) was cooled to 0° C. and carbonic acid hexahydro-furo[2,3-b]furan-3-yl ester 4-nitro-phenyl ester (0.295 g, 1.0 mmol) was added, followed by DIEA (391 μL, 2.18 mmol) and DMAP (cat). The reaction mixture was warmed to rt, and stirred for 1 h. The solvent was removed under reduced pressure and the crude reaction mixture was partitioned between EtOAc and 2N K2CO3(aq). The layers were separated and the organics washed repeatedly with 2N K2CO3(aq). Both epimers of 5-(3,3-Dimethyl-but-ynyl)-3-[[4-(hexahydro-furo[2,3-b]furan-3-yloxycarbonylamino)-cyclohexyl]-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester were isolated by reverse phase HPLC and carried forward wet into the next reaction.

Fuente