Dimethylformamide → 3-(2-Benzyloxy-5-bromo-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester

HRID 237248Notes

Reaction equation

HRID 237248 reaction equation
CN(C=O)C.[C:6]([O:10][C:11]([N:13]1[CH2:16][CH:15]([O:17][C:18]2[CH:23]=[C:22]([Br:24])[CH:21]=[CH:20][C:19]=2[OH:25])[CH2:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7].C([O-])([O-])=O.[Cs+].[Cs+].[CH2:32](Br)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>O>[C:6]([O:10][C:11]([N:13]1[CH2:14][CH:15]([O:17][C:18]2[CH:23]=[C:22]([Br:24])[CH:21]=[CH:20][C:19]=2[O:25][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:16]1)=[O:12])([CH3:9])([CH3:7])[CH3:8]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 7498Benzyl BromideHCID 10796Cesium carbonateHCID 673444423-(5-Bromo-2-hydroxy-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 673463273-(2-Benzyloxy-5-bromo-phenoxy)-azetidine-1-carboxylic acid tert-butyl esterYield 99.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a DMF (10 mL) solution of the title compound of Step C (0.52 g, 1.5 mmol), Cs2CO3 (0.54 g, 1.7 mmol) and KI (0.20 g, 1.20 mmol) was added benzyl bromide (0.20 mL, 0.29 g, 1.7 mmol). After 48 h, H2O was added and the mixture extracted with EtOAc (2×). The combined organics were washed with brine (2×) and dried. Silica gel chromatography (5-20% EtOAc in hexanes) gave 0.65 g (99%) of the title compound as a clear oil. 1H NMR (CDCl3): 7.42-7.36 (m, 3H), 7.34-7.31 (m, 2H), 7.03 (dd, J=8.6, 2.3 Hz, 1H), 6.81 (d, J=8.6 Hz, 1H), 6.70 (d, J=2.3 Hz, 1H), 5.09 (s, 2H), 4.88-4.83 (m, 1H), 4.26 (ddd, J=9.7, 6.5, 0.9 Hz, 2H), 4.05 (dd, J=9.8, 4.0 Hz, 2H), 1.45 (s, 9H).

Workup

  1. extractionthe mixture extracted with EtOAc (2×)
  2. washThe combined organics were washed with brine (2×)
  3. customdried

Sources & evidence

ORD record
ord-d7215fe8e65d40ad849fbdced4b6d264
Source dataset
uspto-grants-2014_02
Patent number
US08642583B2

Reaction notes

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