Hydrochloric Acid → Trandolaprilat

HRID 549439

반응식

HRID 549439 반응식
[OH-].[Na+].O.CC[O:6][C:7]([C@@H:9]([NH:18][C@H:19]([C:21]([N:23]1[C@H:31]([C:32]([OH:34])=[O:33])[CH2:30][C@@H:29]2[C@@H:24]1[CH2:25][CH2:26][CH2:27][CH2:28]2)=[O:22])[CH3:20])[CH2:10][CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)=[O:8].Cl>C(O)C>[CH3:20][C@H:19]([NH:18][C@H:9]([C:7]([OH:8])=[O:6])[CH2:10][CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[C:21]([N:23]1[C@H:31]([C:32]([OH:34])=[O:33])[CH2:30][C@@H:29]2[C@@H:24]1[CH2:25][CH2:26][CH2:27][CH2:28]2)=[O:22]

참가 물질

6

반응물 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 5484727Trandolapril

생성물 1

HCID 5464097Trandolaprilat

시약·촉매·용매 1

HCID 702Ethanol용매

실험 절차

A solution of NaOH (0.96 g, 22.68 mmol; assay=94.52%), water (22 ml), ethanol (22 ml, technical grade, contains ˜5% 2-propanol) and Trandolapril (4.5 g, 10.42 mmol; assay=99.7%) was stirred at an internal temperature ranging from about 20° C. to about 25° C. for 19 hours. After an in process control showed an almost complete saponification (by HPLC), the clear solution was acidified at a temperature ranging from about 20° C. to about 25° C. with 2N aqueous hydrochloric acid to a pH of 3.8 (22.8 mmol; the solution was seeded during acidification and the crystallization started at pH=4.6). The suspension was stirred at a temperature ranging from about 20° C. to about 25° C. (the stirring time in this case after pH adjustment was 47 hours and the pH was adjusted from 3.71 to 3.82 by an addition of 1 drop of 2N aqueous NaOH solution; generally a maximum stirring time of 5 to 6 hours at this pH is sufficient) and then filtered off. The wet product was washed with water (30 ml) and dried in vacuo (1-5 mbar) for 15 hours at 40° C. to give Trandolaprilat (yield: 4.0 g, 9.06 mmol, 86.9%; assay=91.15%; water content: 1.02-1.12%, ethanol content: 7.52-8.44%, 2-propanol content: 0.26-0.29, chloride content=not detected).

후처리

  1. customthe crystallization
  2. customranging from about 20° C. to about 25° C.
  3. waitwas 47 hours
  4. additionthe pH was adjusted from 3.71 to 3.82 by an addition of 1 drop of 2N aqueous NaOH solution
  5. customa maximum stirring time of 5 to 6 hours
  6. filtrationthen filtered off
  7. washThe wet product was washed with water (30 ml)
  8. customdried in vacuo (1-5 mbar) for 15 hours at 40° C.

출처 및 근거

ORD 기록
ord-92dab765688c4437973f7c52918cf84c
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07943655B2

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