Reacción #1702106
ord-cb548be5069e42a4bb4d1f8fb1e42baa
Ecuación de reacción
Reactantes
Reactivos
Disolventes
Condiciones de reacción
Tratamiento posterior
- 1Otrosealed with
- 2Otroa cap
- 3Temperaturathe temperature was increased to 90° C.
- 4TemperaturaThe reaction mixture was further heated to 100° C.
- 5workup.STIRRINGstirred 24 h
- 6Otropartitioned between water and ethyl acetate:hexanes (1:1)
- 7OtroThe layers were separated
- 8Extracciónthe aqueous layer was extracted again with ethyl acetate:hexanes (1:1)
- 9SecadoThe combined organic layers were dried over sodium sulfate
- 10Filtraciónfiltered
- 11Concentraciónconcentrated
Procedimiento
(1S)-4-Methyl-cyclohex-3-ene-1-carboxylic acid chloride (1.8 mmol), 5-(3,3-dimethyl-but-1-ynyl)-3-(1,4-dioxa-spiro[4.5]dec-8-ylamino)-thiophene-2-carboxylic acid methyl ester (336 mg, 0.89 mmol) and DMAP (217 mg, 1.8 mmol) were dissolved in dichloroethane (2.2 mL), sealed with a cap and heated to 80° C. After 2 h, the temperature was increased to 90° C., and the solution was stirred 16 h. The reaction mixture was further heated to 100° C., stirred 24 h and partitioned between water and ethyl acetate:hexanes (1:1). The layers were separated and the aqueous layer was extracted again with ethyl acetate:hexanes (1:1). The combined organic layers were dried over sodium sulfate, filtered and concentrated. Flash chromatography (5% EtOAc:hexanes 5 min then 5-40% EtOAc:hexanes, 20 min, 24 g column) afforded 250 mg (56% yield of the desired 5-(3,3-dimethyl-but-1-ynyl)-3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-(4-methyl-cyclohex-3-enecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester as a white foam.