Tetrahydrofuran → Tert-butyl 3-[1-(3,5-difluorophenyl)-1-hydroxy-2,2-diethylpropyl]azetidine-1-carboxylate
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:18]=[C:19]([F:21])[CH:20]=1)[C:5]([CH:7]1[CH2:10][N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:8]1)=[O:6].[C:22]([Mg]Cl)(C)(C)[CH3:23].[NH4+].[Cl-].[CH2:30]1[CH2:34]O[CH2:32][CH2:31]1>>[F:1][C:2]1[CH:3]=[C:4]([C:5]([CH:7]2[CH2:10][N:9]([C:11]([O:13][C:14]([CH3:15])([CH3:16])[CH3:17])=[O:12])[CH2:8]2)([OH:6])[C:31]([CH2:22][CH3:23])([CH2:30][CH3:34])[CH3:32])[CH:18]=[C:19]([F:21])[CH:20]=1Participants
5
Conditions
- Temperature
- -78 °C
Procedure
To a solution of 3.07 g (10.34 mmol) of tert-butyl 3-(3,5-difluorobenzoyl)azetidine-1-carboxylate in 20 mL of THF, 36.19 mL (36.19 mmol) of tert-butyl magnesium chloride was added and stirred for 3.5 h at −78° C. To the solution was added 8 mL of aq. NH4Cl and the solution was filtered to remove the solid. The filtrate was washed with ether. The combined organic layer was concentrated to remove solvents and residue was purified by silica gel chromatography with hexanes/ethyl acetate to afford the title compound; 1H-NMR(CDCl3) δ 0.897 (s, 9H), 1.425 (s, 9H), 2.234(br, 1H), 3.25 (m, 1H), 3.55 (m, 1H), 3.71 (t, J=8.9 Hz, 1H), 3.97 (t, J=8.4 Hz, 1H), 4.17(m ,1H), 6.53-6.74 (m, 3H).
Workup
- filtrationthe solution was filtered
- customto remove the solid
- washThe filtrate was washed with ether
- concentrationThe combined organic layer was concentrated
- customto remove solvents and residue
- customwas purified by silica gel chromatography with hexanes/ethyl acetate
Sources & evidence
- ORD record
- ord-bc3320d818bb4b5c9719c03e656f66c9
- Source dataset
- uspto-grants-2009_02
- Patent number
- US07485732B2
Reaction notes
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