Dimethylformamide → Clevidipine, (R)-
Reaction equation
[CH3:1][C:2]1[NH:3][C:4]([CH3:23])=[C:5]([CH2:19]C(O)=O)[C@H:6]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[C:12]=2[Cl:18])[C:7]=1[C:8]([OH:10])=[O:9].[C:24](=O)(O)[O-:25].[Na+].[C:29]([O:34][CH2:35]Cl)(=[O:33])[CH2:30][CH2:31][CH3:32].CN(C=[O:41])C>>[Cl:18][C:12]1[C:13]([Cl:17])=[CH:14][CH:15]=[CH:16][C:11]=1[C@@H:6]1[C:5]([C:19]([O:25][CH3:24])=[O:41])=[C:4]([CH3:23])[NH:3][C:2]([CH3:1])=[C:7]1[C:8]([O:10][CH2:35][O:34][C:29](=[O:33])[CH2:30][CH2:31][CH3:32])=[O:9]Participants
Conditions
- Temperature
- 80 °C
Procedure
To a stirred mixture of (4S)-1,4-dihydro-2,6-dimethyl-4-(2',3'-dichorophenyl)-5-carboxymethyl-3-pyridinecarboxylic acid (2.0 g, 5.61 mmol) and sodium bicarbonate (0.96 g, 11.4 mmol) in DMF (100 ml) under nitrogen atmosphere was added chloromethyl butyrate (1.16 g, 8.5 mmol). The reaction mixture was heated at 80° C. for 23 h. Workup by filtration followed by evaporation of solvent. The crude residue was dissolved in dichloromethane and washed with sodium bicarbonatesolution. The organic phase was dried over sodium sulfate and evaporated. Recrystallization first from a mixture of 45% ethylacetate in isooctane followed by diisopropylether gave colorless crystals (1.08 g, 42%), mp. 128°-129° C. NMR spectral data are identical with the data of the racemate as shown in Example 3. [α]D20 =-21.50 (1 % in methanol).
Workup
- filtrationWorkup by filtration
- customfollowed by evaporation of solvent
- dissolutionThe crude residue was dissolved in dichloromethane
- washwashed with sodium bicarbonatesolution
- dry with materialThe organic phase was dried over sodium sulfate
- customevaporated
- customRecrystallization
- additionfirst from a mixture of 45% ethylacetate in isooctane
Sources & evidence
- ORD record
- ord-c9e01bd588bd470c9254e44a5f9f9efc
- Source dataset
- uspto-grants-1999_01
- Patent number
- US05856346
Reaction notes
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