Potassium Carbonate → Tert-butyl 3-((2-chloro-5-fluoro-4-(methoxycarbonyl)phenoxy)methyl)azetidine-1-carboxylate

HRID 1849874Notes

Reaction equation

[Cl:1][C:2]1[C:3](F)=[CH:4][C:5]([F:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[OH:14][CH2:15][CH:16]1[CH2:19][N:18]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:17]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:1][C:2]1[CH:11]=[C:6]([C:7]([O:9][CH3:10])=[O:8])[C:5]([F:12])=[CH:4][C:3]=1[O:14][CH2:15][CH:16]1[CH2:19][N:18]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:17]1

Participants

Conditions

Temperature: 30 °C

Procedure

A mixture of methyl 5-chloro-2,4-difluorobenzoate (2.2 g, 10.7 mmol), tert-butyl 3-(hydroxymethyl)azetidine-1-carboxylate (2.0 g, 10.7 mmol) and potassium carbonate (4.43 g, 32.1 mmol) in DMF (30 mL) was stirred at 30° C. for 16 h. The mixture was quenched by water and extracted with EtOAc (50 mL×3). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was purified by silica gel column (eluting with petroleum ether/ethyl acetate, from 20/1 to 3/1) to give tert-butyl 3-((2-chloro-5-fluoro-4-(methoxycarbonyl)phenoxy)methyl)azetidine-1-carboxylate (1.2 g, 30%) as a pale yellow oil. LCMS (ESI) m/z: 318.0 [M-56+H].

Workup

customThe mixture was quenched by water
extractionextracted with EtOAc (50 mL×3)
washThe combined organic layers were washed with brine
dry with materialdried over anhydrous sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe resulting residue was purified by silica gel column (eluting with petroleum ether/ethyl acetate, from 20/1 to 3/1)

Sources & evidence

ORD record: ord-010e9c43991f4aaaa9ee7980611b05c4
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08952169B2

Reaction notes

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