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

HRID 8478

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>[Cl-].C([N+](C)(C)C)C1C=CC=CC=1.CN(C=O)C>[CH2:16]([O:15][C:13](=[O:14])[C:12](=[CH:11][N:6]1[C:5]2[CH:23]=[CH:24][C:25]([F:28])=[C:26]([F:27])[C:4]=2[O:9][CH2:8][C@@H:7]1[CH3:10])[C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH3:17]

Participants

Conditions

Temperature: 60 °C

Procedure

Potassium hydroxide (180 mg) and benzyltrimethylammonium chloride (60.7 mg) were dissolved in DMF (15 ml) by heating to 60° C. and a solution (5 ml) 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 was added thereto. The obtained mixture was stirred at the same temperature for 7 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, 899 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-09aad72a49c54100a1770b7ca03a3bcc
Source dataset: uspto-grants-2006_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07087778B2

Linked notes

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