Water → 1,1-Dimethylethyl 3-(5-bromo-2-cyanophenoxy)-1-azetidinecarboxylate

HRID 1850083Notes

Reaction equation

HRID 1850083 reaction equation
[Br:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4](F)[CH:3]=1.[C:11]([O:15][C:16]([N:18]1[CH2:21][CH:20]([OH:22])[CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].[H-].[Na+].O>CN(C=O)C.CCOC(C)=O>[C:11]([O:15][C:16]([N:18]1[CH2:21][CH:20]([O:22][C:4]2[CH:3]=[C:2]([Br:1])[CH:9]=[CH:8][C:5]=2[C:6]#[N:7])[CH2:19]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 7360294-Bromo-2-fluorobenzonitrileHCID 2756801Tert-butyl 3-hydroxyazetidine-1-carboxylate

Product 1

HCID 673451981,1-Dimethylethyl 3-(5-bromo-2-cyanophenoxy)-1-azetidinecarboxylateYield 79.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-bromo-2-fluoro-benzonitrile (1.0 g, 5.0 mmol) and 3-hydroxy-azetidine-1-carboxylic acid tert-butyl ester (0.95 g, 5.5 mmol) in DMF (15 mL) at 0° C., was added NaH (60% in mineral oil, 130 mg, 5.5 mmol). After 18 h, H2O and EtOAc were added and the organic portion washed with brine (3×) and dried to provide the title compound (1.4 g, 79%). MS (ESI): mass calcd. for C15H17BrN2O3, 352.0. m/z found, 377.1 [M+Na]+. 1H NMR (CDCl3): 7.48 (d, J=8.2 Hz, 1H), 7.25 (dd, J=8.2, 1.7 Hz, 1H), 6.79 (d, J=1.6 Hz, 1H), 5.00-4.92 (m, 1H), 4.38 (ddd, J=9.9, 6.4, 1.1 Hz, 2H), 4.11 (dd, J=10.0, 3.8 Hz, 2H), 1.48 (s, 9H).

Workup

  1. washthe organic portion washed with brine (3×)
  2. customdried

Sources & evidence

ORD record
ord-ab00c5a4a9544ae38690a359651d664e
Source dataset
uspto-grants-2015_02
Patent number
US08957059B2

Reaction notes

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