Methanol → (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 993338ノート

反応式

HRID 993338 の反応式
C(O[CH2:5][C@@H:6]([C@@H:12]1[CH2:16][O:15][C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([O:23]C(=O)C)[C:18]=2[CH3:27])=[N:13]1)[O:7]S(C)(=O)=O)(=O)C.CO.[C:30]([NH:34][C:35]([C@@H:37]1[CH2:46][C@H:45]2[C@H:40]([CH2:41][CH2:42][CH2:43][CH2:44]2)[CH2:39][NH:38]1)=[O:36])([CH3:33])([CH3:32])[CH3:31].C(=O)([O-])[O-].[K+].[K+]>O>[C:30]([NH:34][C:35]([C@@H:37]1[CH2:46][C@H:45]2[C@H:40]([CH2:41][CH2:42][CH2:43][CH2:44]2)[CH2:39][N:38]1[CH2:5][C@H:6]([C@@H:12]1[CH2:16][O:15][C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([OH:23])[C:18]=2[CH3:27])=[N:13]1)[OH:7])=[O:36])([CH3:33])([CH3:31])[CH3:32]

参加物

6

反応物 4

HCID 887MethanolHCID 11430Potassium CarbonateHCID 454736(3S,4aS,8aS)-N-(tert-Butyl)decahydroisoquinoline-3-carboxamideHCID 10524958(2R)-1-acetoxy-2-((4S)-2-(3-acetoxy-2-methylphenyl)-4,5-dihydrooxazol-4-yl)-2-methanesulfonyloxyethane

生成物 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-carboxamide

試薬・触媒・溶媒 1

HCID 962Water溶媒2 回

反応条件

温度
50 °C

実験手順

The crude product of Example 3, (2R)-1-acetoxy-2-((4S)-2-(3-acetoxy-2-methylphenyl)-4,5-dihydrooxazol-4-yl)-2methanesulfonyloxyethane, 18′(1.98 kg, 3.30 mol) was suspended in a mixed solvent of methanol (6.50 L) and water (6.50 L), and (3S, 4aS, 8aS)-decahydroisoquinoline-3-carboxylic acid t-butylamide, 642 g, 2.62 mol) and potassium carbonate (1.36 kg, 9.81 mol) were successively added, which was followed by stirring at 50° C. for 5.5 h ours. Water (6.50 L) was added to cool the reaction mixture to room temperature and the resulting crystals were collected by filtration. These crude crystals were again suspended in water (6.50 L), stirred, washed and collected by filtration. The obtained crystals were re-suspended in methyl isobutyl ketone (10.0 L) and the suspension was subjected to azeotropic dehydration. The resulting slurry was cooled to room temperature and crystals were collected by filtration to give 902 g (1.07 mol) of the title compound, as colorless crystals.

後処理

  1. additionwere successively added
  2. temperatureto cool the reaction mixture to room temperature
  3. filtrationthe resulting crystals were collected by filtration
  4. stirringstirred
  5. washwashed
  6. filtrationcollected by filtration
  7. temperatureThe resulting slurry was cooled to room temperature
  8. filtrationcrystals were collected by filtration

出典と根拠

ORDレコード
ord-d8ba6c6ecc0a45eabebe56c977404a2c
出典データセット
uspto-grants-2002_10
特許番号
US06472534B2

反応ノート

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