Methanol → 1-Boc-3-(4-bromophenyl)-3-hydroxyazetidine

HRID 1961525Notes

Reaction equation

[OH:1][C:2]1([C:13]2[CH:18]=[CH:17][C:16]([Si](C)(C)C)=[CH:15][CH:14]=2)[CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:3]1.[K+].[Br-:24].CO.ClN1C(=O)CCC1=O>C(O)(=O)C>[Br:24][C:16]1[CH:17]=[CH:18][C:13]([C:2]2([OH:1])[CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:3]2)=[CH:14][CH:15]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of tert-butyl 3-hydroxy-3-(4-(trimethylsilyl)phenyl)azetidine-1-carboxylate (Preparation 3, 45 g, 0.14 mol) and KBr (25 g, 0.21 mol) in acetic acid (10 and MeOH (100 mL) was heated at 60° C. for 20 minutes. Then N-chlorosuccinimide (22.4 g, 0.17 mol) was added to the reaction mixture and stirred at 60° C. for 2 hours. LC/MS indicated the reaction was complete (only product peak). After cooling to ambient temperature, the mixture was poured into ice-water (1 L). The mixture was extracted with CHCl3 (2×800 mL). The combined organics were washed with 3M NaOH (2×600 mL), water (600 mL), dried over sodium sulfate, filtered and concentrated. The crude product was washed with ether to afford the desired product (35 g, 76% yield). 1H NMR (CDCl3) δ 7.5 (d, 2H), 7.4 (d, 2H), 4.2 (s, 4H), 3.4 (s, 1H), 1.4 (s, 9H).

Workup

temperatureAfter cooling to ambient temperature
extractionThe mixture was extracted with CHCl3 (2×800 mL)
washThe combined organics were washed with 3M NaOH (2×600 mL), water (600 mL)
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated
washThe crude product was washed with ether

Sources & evidence

ORD record: ord-cb261cb852c2433fba34efbfa855d617
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415310B2

Reaction notes

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