Thiophene → HCID 86697900, compound

Temperature

-78 °C

A −78° C. solution of thiophene (17 g, 203 mmol) in tetrahydrofuran (250 mL) under nitrogen is treated drop wise with a solution of n-butyl lithium (81 mL, 203 mmol, 1.6 M in hexanes) and the reaction is stirred at −78° C. for 10 minutes. In a separate flask, a −78° C. solution of benzyl 3,3a,4,6-tetrahydropyrrolo[3,4-c]isoxazole-5-carboxylate (25 g, 101 mmol) in tetrahydrofuran (500 mL) under nitrogen is treated with boron trifluoride ether complex (19 mL, 152 mmol) and the mixture is stirred for 10 minutes. The solution is added by cannula to the organolithium solution generated above at −78° C. and the resulting mixture is stirred for 1 hour at −78° C. The reaction is quenched with saturated ammonium chloride and warmed to room temperature. The aqueous layer is separated, the organic layer is dried over magnesium sulfate and the solvent is removed under vacuum. The crude product is purified over silica gel using a 5 to 50% gradient of ethyl acetate/hexanes gradient to give the title compound (22 g, 65%). ES/MS (m/e): 331 (M+H).

1. stirringthe mixture is stirred for 10 minutes
2. customgenerated above at −78° C.
3. stirringthe resulting mixture is stirred for 1 hour at −78° C
4. customThe reaction is quenched with saturated ammonium chloride
5. temperaturewarmed to room temperature
6. customThe aqueous layer is separated
7. dry with materialthe organic layer is dried over magnesium sulfate
8. customthe solvent is removed under vacuum
9. customThe crude product is purified over silica gel using a 5 to 50% gradient of ethyl acetate/hexanes gradient

ORD record

ord-1bcb602b40984d72b1b5d06b14e114d2

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08629270B2