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 2186483Notes

Reaction equation

HRID 2186483 reaction equation
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]

Participants

6

Reactant 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-methanesulfonyloxyethane2×

Product 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

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
50 °C

Procedure

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 hours. 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.

Workup

  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

Sources & evidence

ORD record
ord-26b9890883934e4a9f7649dd663b590e
Source dataset
uspto-grants-2002_06
Patent number
US06403799B1

Reaction notes

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