Water → (S)-Diethyl (7,8-Difluoro-3-Methyl-3,4-Dihydro-2H-[1,4]Benzoxazin-4-Yl)Methylene-Malonate

HRID 985696Notes

Reaction equation

[OH-].[K+].F[C:4]1[C:26]([F:27])=[C:25]([F:28])[CH:24]=[CH:23][C:5]=1[N:6]([CH:11]=[C:12]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:13]([O:15][CH2:16][CH3:17])=[O:14])[C@@H:7]([CH3:10])[CH2:8][OH:9].C(OC=C(C(OCC)=O)C(OCC)=O)C.O>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C>[F:28][C:25]1[CH:24]=[CH:23][C:5]2[N:6]([CH:11]=[C:12]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:13]([O:15][CH2:16][CH3:17])=[O:14])[C@@H:7]([CH3:10])[CH2:8][O:9][C:4]=2[C:26]=1[F:27]

Participants

Conditions

Temperature: 60 °C

Procedure

Potassium hydroxide (180 mg) and tetrabutylammonium hydrogensulfate (90.4 mg) were dissolved in DMF (15 ml) by heating to 60° C. and a solution of diethyl [2,3,4-trifluoro[(1S)-2-hydroxy-1-methylethyl]anilino]methylenemalonate (1 g, 99.8% ee) and diethyl ethoxymethylenemalonate (120 mg) in DMF 85 ml) was added thereto. The obtained mixture was stirred at the same temperature for 2 hours. After adding water, the liquid reaction mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. After evaporating the solvent, the obtained residue was subjected to silica gel column chromatography. Thus, 852 mg (99.8% ee) of the title compound was obtained as a yellow oily substance. Various spectral data was identical with those described in Japanese Patent No. 2,769,174.

Workup

customthe liquid reaction mixture
extractionwas extracted with ethyl acetate
dry with materialThe organic layer was dried over anhydrous magnesium sulfate
customAfter evaporating the solvent

Sources & evidence

ORD record: ord-3998403c7ebf434c9609f7ef7a449382
Source dataset: uspto-grants-2005_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06872823B1

Reaction notes

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