Hydrochloric Acid → Trandolapril

HRID 1009813

反応式

HRID 1009813 の反応式
[NH:1]1[C@@H:9]2[C@H:4]([CH2:5][CH2:6][CH2:7][CH2:8]2)[CH2:3][C@H:2]1[C:10]([OH:12])=[O:11].C(N(CC)CC)C.[CH3:20][CH2:21][O:22][C:23]([CH:25]([N:34]1C(=O)O[C:36](=[O:37])[CH:35]1[CH3:41])[CH2:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:24].Cl>ClCCl.O>[CH3:20][CH2:21][O:22][C:23]([C@@H:25]([NH:34][C@H:35]([C:36]([N:1]1[C@H:2]([C:10]([OH:12])=[O:11])[CH2:3][C@@H:4]2[C@@H:9]1[CH2:8][CH2:7][CH2:6][CH2:5]2)=[O:37])[CH3:41])[CH2:26][CH2:27][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)=[O:24]

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 4639425N-[1-(S)-Ethoxycarbonyl-3-phenylpropyl]-L-alanine-N-carboxyanhydride2 回HCID 7018901(2S,3aR,7aS)-Octahydro-1H-indole-2-carboxylic acid

生成物 1

HCID 5484727Trandolapril収率 30.7%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

(2S,3aR,7aS) octahydro-1H-indole-2-carboxylic acid (65 gms 0.384 moles) was stirred in dichloromethane (200 ml), triethyl amine (30 ml) was added under stirring at ambient temperature for 30 mins. N-[1-(S)-ethoxy carbonyl-3-phenyl propyl]-L-alanine N-carboxy anhydride (110 gms; 0.378 moles) (residue from Step A) dissolved in dichloromethane (50 ml) was added dropwise to the reaction mass at ambient temperature and further stirred for 3 hrs. Water (500 ml) was added and the reaction mass was cooled to 15° C., pH of the reaction mass was adjusted to 4.2 using 2N HCl. The organic layer was separated and aqueous layer reextracted with dichloromethane. The combined organic layer was dried with sodium sulphate and concentrated to residue. The residue was dissolved in ethylacetate at reflux temperature. The reaction mass was cooled to ambient temperature. The resulting solid was filtered and dried under vacuum to get 50 gms of Trandolapril (HPLC purity 99.5%)

後処理

  1. additionwas added dropwise to the reaction mass at ambient temperature
  2. stirringfurther stirred for 3 hrs
  3. temperaturethe reaction mass was cooled to 15° C.
  4. customThe organic layer was separated
  5. dry with materialThe combined organic layer was dried with sodium sulphate
  6. concentrationconcentrated to residue
  7. dissolutionThe residue was dissolved in ethylacetate
  8. temperatureat reflux temperature
  9. temperatureThe reaction mass was cooled to ambient temperature
  10. filtrationThe resulting solid was filtered
  11. customdried under vacuum

出典と根拠

ORDレコード
ord-0ee4d9cde17e43c3adf3bdc46d940d6c
出典データセット
uspto-grants-2011_07
特許番号
US07973173B2

関連ノート

読み込み中…