Ethyl 2-(diphenylmethyleneamino)acetate → 2-(Benzhydrylidene-amino)-3-(3-difluoromethoxy-phenyl)-propionic acid ethyl ester

HRID 1524878Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:20])[CH2:5][N:6]=[C:7]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH3:2].[F:21][CH:22]([F:32])[O:23][C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=1)[CH2:27]Br.C(N=P1(N(CC)CC)N(C)CCCN1C)(C)(C)C>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:1]([O:3][C:4](=[O:20])[CH:5]([N:6]=[C:7]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[CH2:27][C:26]1[CH:29]=[CH:30][CH:31]=[C:24]([O:23][CH:22]([F:21])[F:32])[CH:25]=1)[CH3:2]

Participants

Conditions

Temperature: -78 °C

Procedure

N-(Diphenylmethylene)Glycine ethyl ester (500 mg, 1.87 mmol), Tetrabuylammonium Bromide (63 mg, 0.187 mmol) and 3-(Difluoromethoxy)benzyl bromide (0.5 mL, 1.87 mmol) were placed in a flask. The flask was evacuated and backfilled with argon. Anhyd dichloromethane was added to the flask, and the reaction was cooled in dry-ice acetone bath to −78° C. 2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine (0.7 mL, 2.44 mmol) was added slowly under argon at −78° C. The reaction was allowed to stir at −78° C. for 30 minutes, and then warmed to room temperature over 16 h. The solvent was removed under vacuum. The residue was pre-adsorbed on to SiO2 and the product was isolated via SiO2 to yield 700 mg of light yellow oil. MS 424.0 (M+H)+.

Workup

customThe flask was evacuated
additionAnhyd dichloromethane was added to the flask
temperaturewarmed to room temperature over 16 h
customThe solvent was removed under vacuum
customthe product was isolated via SiO2

Sources & evidence

ORD record: ord-8991cc57d648485e946e871eeaddf783
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09079860B2

Reaction notes

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