Ammonium Chloride → Tert-butyl 3-[1-(3,5-difluorophenyl)-1-hydroxy-2,2-dimethylpropyl]azetidine-1-carboxylate

HRID 602702Notes

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)([CH3:25])([CH3:24])[CH3:23].[NH4+].[Cl-]>C1COCC1>[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:22]([CH3:25])([CH3:24])[CH3:23])[CH:18]=[C:19]([F:21])[CH:20]=1

Participants

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-06e5cc734c194ddf838c98867f1648cd
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07906503B2

Reaction notes

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