Dimethylformamide → Clevidipine, (R)-

HRID 341870ノート

反応式

HRID 341870 の反応式
[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]

参加物

5

反応物 4

HCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 2725008Chloromethyl butanoateHCID 22884798(4s)-1,4-Dihydro-2,6-dimethyl-4-(2',3'-dichorophenyl)-5-carboxymethyl-3-pyridinecarboxylic acid

生成物 1

HCID 193993Clevidipine, (R)-収率 42%

反応条件

温度
80 °C

実験手順

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).

後処理

  1. filtrationWorkup by filtration
  2. customfollowed by evaporation of solvent
  3. dissolutionThe crude residue was dissolved in dichloromethane
  4. washwashed with sodium bicarbonatesolution
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. customevaporated
  7. customRecrystallization
  8. additionfirst from a mixture of 45% ethylacetate in isooctane

出典と根拠

ORDレコード
ord-c9e01bd588bd470c9254e44a5f9f9efc
出典データセット
uspto-grants-1999_01
特許番号
US05856346

反応ノート

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