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

HRID 985695Notes

Reaction equation

HRID 985695 reaction equation
CC(C)([O-])C.[K+].F[C:8]1[C:18]([F:19])=[C:17]([F:20])[CH:16]=[CH:15][C:9]=1[NH:10][C@@H:11]([CH3:14])[CH2:12][OH:13].C(O[CH:24]=[C:25]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[C:26]([O:28][CH2:29][CH3:30])=[O:27])C>CN(C=O)C>[F:20][C:17]1[CH:16]=[CH:15][C:9]2[N:10]([CH:24]=[C:25]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[C:31]([O:33][CH2:34][CH3:35])=[O:32])[C@@H:11]([CH3:14])[CH2:12][O:13][C:8]=2[C:18]=1[F:19]

Participants

5

Reactant 3

HCID 6871Diethyl (ethoxymethylene)malonateHCID 11401466(2S)-2-(2,3,4-Trifluoroanilino)propanolHCID 23665647Potassium tert-butoxide

Product 1

HCID 11089557(S)-Diethyl (7,8-Difluoro-3-Methyl-3,4-Dihydro-2H-[1,4]Benzoxazin-4-Yl)Methylene-MalonateYield 65.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To DMF (2 ml) was added potassium tertiary-butoxide (226 mg) under ice-cooling. After dropping a solution of the compound (100 mg) obtained in Example 51 and diethyl ethoxymethylenemalonate (293 mg) in DMF (0.5 ml), the resultant mixture was stirred at room temperature for 18 hours. After treating in a conventional manner, the obtained residue was subjected to silica gel column chromatography to thereby give 113 mg (65%) of the title compound. The physical constants of the obtained compounds was identical with those described in Japanese Patent No. 2,769,174.

Workup

  1. temperaturecooling
  2. additionAfter treating in a conventional manner

Sources & evidence

ORD record
ord-543628e6ce34474a86750f9ac3e39d36
Source dataset
uspto-grants-2005_03
Patent number
US06872823B1

Reaction notes

Loading…