Acetic Acid → (3S,4aS,8aS)-N-tert-butyl-2-[(2R)-2-hydroxy-2-[(4S)-2-(3-hydroxy-2-methylphenyl)-4,5-dihydro-1,3-oxazol-4-yl]ethyl]-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinoline-3-carboxamide

HRID 1069496노트

반응식

HRID 1069496 반응식
C(O)(=O)C.C(=O)([O-])O.[K+].[C:10]([NH:14][C:15]([C@@H:17]1[CH2:26][C@H:25]2[C@H:20]([CH2:21][CH2:22][CH2:23][CH2:24]2)[CH2:19][NH:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].CS([O:31][C@@H:32]1[C@@H:38]([NH:39][C:40](=[O:52])[C:41]2[CH:46]=[CH:45][CH:44]=[C:43]([O:47]C(=O)C)[C:42]=2[CH3:51])[CH2:37]OC(C)(C)O[CH2:33]1)(=O)=O>>[C:10]([NH:14][C:15]([C@@H:17]1[CH2:26][C@H:25]2[C@H:20]([CH2:21][CH2:22][CH2:23][CH2:24]2)[CH2:19][N:18]1[CH2:33][C@H:32]([C@@H:38]1[CH2:37][O:52][C:40]([C:41]2[CH:46]=[CH:45][CH:44]=[C:43]([OH:47])[C:42]=2[CH3:51])=[N:39]1)[OH:31])=[O:16])([CH3:13])([CH3:11])[CH3:12]

참가 물질

5

반응물 4

HCID 176Acetic AcidHCID 454736(3S,4aS,8aS)-N-(tert-Butyl)decahydroisoquinoline-3-carboxamide2회HCID 516893Potassium BicarbonateHCID 10787996(5R,6S)-N-(5-methanesulfonyloxy-2,2-dimethyl-1,3-dioxepan-6-yl)-3-acetoxy-2-methylbenzamide

생성물 1

HCID 10695174(3S,4aS,8aS)-N-tert-butyl-2-[(2R)-2-hydroxy-2-[(4S)-2-(3-hydroxy-2-methylphenyl)-4,5-dihydro-1,3-oxazol-4-yl]ethyl]-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinoline-3-carboxamide수율 46%

반응 조건

온도
45 °C

실험 절차

Production of compound [13] (Step 9) Acetic acid (14.0 ml, 245 mmol) was added to the mixture obtained in Example 8 at not more than 10° C. to make the mixture acidic, and potassium hydrogencarbonate (25.0 g, 250 mmol) and (3S, 4aS, 8aS)-decahydroisoquinoline-3-carboxylic acid t-butylamide (compound [12], 13.7 g, 57.6 mmol) were successively added. The mixture was stirred at 45° C. for 6 hours to give a pale yellow suspension. The suspension was concentrated to ⅕ and water (340 ml) was added. The suspension was stirred for one hour at room temperature. The resulting crystals were collected by filtration and washed successively with water (200 ml) and butyl acetate (340 ml). The crystals were dried under reduced pressure at 60° C. to give colorless crystals of (3S, 4aS, 8aS)-2-{(2R)-2-[(4S)-2-(3-hydroxy-2-methylphenyl)-4,5-dihydrooxazol-4-yl]-2-hydroxyethyl}decahydroisoquinoline-3-carboxylic acid t-butylamide (compound [13], 17.3 g, yield 46%, from compound [9]), melting point 240° C.

후처리

  1. customto give a pale yellow suspension
  2. concentrationThe suspension was concentrated
  3. additionwater (340 ml) was added
  4. stirringThe suspension was stirred for one hour at room temperature
  5. filtrationThe resulting crystals were collected by filtration
  6. washwashed successively with water (200 ml) and butyl acetate (340 ml)
  7. customThe crystals were dried under reduced pressure at 60° C.

출처 및 근거

ORD 기록
ord-c2feb9ce37f34e9a9b1ce86f9718c7f6
출처 데이터셋
uspto-grants-2001_06
특허 번호
US06252085B1

반응 노트

불러오는 중…