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

HRID 458209Notes

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: 70 °C

Procedure

Potassium hydroxide (180 mg) and benzyl trimethylammonium chloride (49.5 mg) were dissolved in DMF (15 ml) by heating to 70° 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 (5 ml) was added thereto. The obtained mixture was stirred at the same temperature for 4 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, 871 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-1fbb1fce547c496486771ceaea5ab332
Source dataset: uspto-grants-2007_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07189847B2

Reaction notes

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