Boron trifluoride → Benzyl 6a-phenyl-3,3a,4,6-tetrahydro-1H-pyrrolo[3,4-c]isoxazole-5-carboxylate

HRID 470214Notes

Reaction equation

B(F)(F)F.[N:5]1[O:6][CH2:7][CH:8]2[CH2:12][N:11]([C:13]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[O:14])[CH2:10][C:9]=12.[C:23]1([Mg]Br)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>O1CCCC1>[C:23]1([C:9]23[CH2:10][N:11]([C:13]([O:15][CH2:16][C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)=[O:14])[CH2:12][CH:8]2[CH2:7][O:6][NH:5]3)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Boron trifluoride (30.8 mL, 244 mmol) is added to a −50° C. solution of benzyl 3,3a,4,6-tetrahydropyrrolo[3,4-c]isoxazole-5-carboxylate (40 g, 162 mmol) in tetrahydrofuran (200 mL). The mixture is stirred for 10 minutes and the solution is added to phenyl magnesium bromide (325 mL, 325 mmol, 1 M in tetrahydrofuran) at −50° C., warmed to 0° C., and stirred for 4 hours. The reaction is quenched with saturated ammonium chloride (200 mL) and 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% ethyl acetate/hexanes gradient to give the title compound (31 g, 59%). ES/MS (m/e): 325 (M+H).

Workup

stirringstirred for 4 hours
customThe reaction is quenched with saturated ammonium chloride (200 mL)
customthe aqueous layer is separated
dry with materialThe organic layer is dried over magnesium sulfate
customthe solvent is removed under vacuum
customThe crude product is purified over silica gel using a 5 to 50% ethyl acetate/hexanes gradient

Sources & evidence

ORD record: ord-37a76f4736a445e5b2ea4328c7ac15c0
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08629270B2

Reaction notes

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