Water → 3-(5-Chloro-2-ethoxycarbonylmethoxy-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester

HRID 237306Notes

Reaction equation

HRID 237306 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=2[OH:20])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].[C:27]([O:30][CH2:31][CH2:32]Br)(=[O:29])[CH3:28].O>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH:10]([O:12][C:13]2[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=2[O:20][CH2:28][C:27]([O:30][CH2:31][CH3:32])=[O:29])[CH2:11]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 135641-Acetoxy-2-bromoethaneHCID 673429093-(5-Chloro-2-hydroxy-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 673467163-(5-Chloro-2-ethoxycarbonylmethoxy-phenoxy)-azetidine-1-carboxylic acid tert-butyl esterYield 101.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 3-(5-Chloro-2-hydroxy-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester (1.5 g, 5.0 mmol) in DMF (20 mL) was added Cs2CO3 (2.1 g, 6.4 mmol), KI (0.84 g, 5.0 mmol) and bromoethyl acetate (0.84 g, 0.55 mL, 5.0 mmol). After 18 h, H2O was added and the mixture extracted with EtOAc (2×). The combined organics were washed with brine and dried. Silica gel chromatography (5-30% EtOAc in hexanes) gave 1.95 g (99%) of the title compound as a clear oil. 1H NMR (CDCl3): 6.91 (dd, J=8.7, 2.4 Hz, 1H), 6.79 (d, J=8.7 Hz, 1H), 6.58 (d, J=2.4 Hz, 1H), 4.91-4.87 (m, 1H), 4.65 (s, 2H), 4.32-4.25 (m, 4H), 4.01 (dd, J=10.5, 4.2 Hz, 2H), 1.44 (s, 9H), 1.30 (t, J=7.1 Hz, 3H).

Workup

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

Sources & evidence

ORD record
ord-0332a41b701a46da87e8235edf3d21bc
Source dataset
uspto-grants-2014_02
Patent number
US08642583B2

Reaction notes

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