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

HRID 985698Notes

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>[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 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 ethylacetate. 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 ethylacetate
dry with materialThe organic layer was dried over anhydrous magnesium sulfate
customAfter evaporating the solvent

Sources & evidence

ORD record: ord-fb71d23355514dc3a04f69f30921e37c
Source dataset: uspto-grants-2005_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06872823B1

Reaction notes

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