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

HRID 237277Notes

Reaction equation

HRID 237277 reaction equation
[Cl:1][C:2]1[CH:9]=[C:8]([F:10])[C:5]([CH:6]=[O:7])=[C:4](F)[CH:3]=1.[C:12]([O:16][C:17]([N:19]1[CH2:22][CH:21]([OH:23])[CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].[H-].[Na+].O>CN(C=O)C.CCOC(C)=O>[C:12]([O:16][C:17]([N:19]1[CH2:22][CH:21]([O:23][C:4]2[CH:3]=[C:2]([Cl:1])[CH:9]=[C:8]([F:10])[C:5]=2[CH:6]=[O:7])[CH2:20]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 2756801Tert-butyl 3-hydroxyazetidine-1-carboxylateHCID 27735124-Chloro-2,6-difluorobenzaldehyde

Product 1

HCID 873651953-(5-Chloro-3-fluoro-2-formyl-phenoxy)-azetidine-1-carboxylic acid tert-butyl esterYield 15.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the title compound of Step A (270 mg, 1.5 mmol) and 3-hydroxy-azetidine-1-carboxylic acid tert-butyl ester (270 mg, 1.5 mmol) in dry DMF (10 mL) at 0° C. was added NaH (60% in mineral oil, 22 mg, 1.5 mmol). After 18 h, H2O and EtOAc were added and the aqueous layer was extracted with EtOAc. The combined organic extracts were dried and concentrated. The crude residue was purified by RP HPLC to provide the title compound (75 mg, 15%). MS (ESI): mass calcd. for C15H17ClFNO4, 329.1; m/z found, 274.0 [M+H-56]+. 1H NMR (CDCl3): 10.4 (s, 1H), 6.84 (dd, J=10.0, 1.6 Hz, 1H), 6.39 (dd, J=1.4, 1.3 Hz, 1H), 5.00-4.92 (m, 1H), 4.38 (dd, J=9.9, 6.3 Hz, 2H), 4.08 (dd, J=10.7, 4.0 Hz, 2H), 1.46 (s, 9H).

Workup

  1. extractionthe aqueous layer was extracted with EtOAc
  2. customThe combined organic extracts were dried
  3. concentrationconcentrated
  4. customThe crude residue was purified by RP HPLC

Sources & evidence

ORD record
ord-e63c643616344de09c8a90bf54d98707
Source dataset
uspto-grants-2014_02
Patent number
US08642583B2

Reaction notes

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