Ethyl Acetate → 1-Benzhydryl-3-(benzofuran-7-yloxy)-azetidine

HRID 83065Notes

Reaction equation

C(=O)([O-])[O-].[K+].[K+].[O:7]1[C:11]2[C:12]([OH:16])=[CH:13][CH:14]=[CH:15][C:10]=2[CH:9]=[CH:8]1.CS(O[CH:22]1[CH2:25][N:24]([CH:26]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:23]1)(=O)=O.C(OCC)(=O)C>CN(C=O)C.O>[CH:26]([N:24]1[CH2:25][CH:22]([O:16][C:12]2[C:11]3[O:7][CH:8]=[CH:9][C:10]=3[CH:15]=[CH:14][CH:13]=2)[CH2:23]1)([C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

Conditions

Temperature: 90 °C

Procedure

Potassium carbonate (348 mg, 2.52 mmol) and benzofuran-7-ol (169 mg, 1.26 mmol) were successively added to a solution of 1-benzhydrylazetidin-3-yl methanesulfonate (400 mg, 1.26 mmol) in DMF (8 mL). The reaction mixture was stirred overnight at 90° C. and then diluted by addition of ethyl acetate (20 mL) and water (20 mL). The aqueous phase was separated and extracted with ethyl acetate (4×50 mL). The combined organic phases were washed with a saturated solution of sodium chloride (5×50 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel using petroleum ether/dichloromethane (1:0 to 2:8 to 0:1) as eluent. The title product was obtained as a yellow oil (350 mg, 69%).

Workup

customThe aqueous phase was separated
extractionextracted with ethyl acetate (4×50 mL)
washThe combined organic phases were washed with a saturated solution of sodium chloride (5×50 mL)
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated to dryness
customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record: ord-99bcafdfe366442baa77e22fdf385538
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846711B2

Reaction notes

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