Methylamine → (3S,4aS,8aS)-2-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N-tert-butyldecahydroisoquinoline-3-carboxamide

HRID 376010Notes

Reaction equation

HRID 376010 reaction equation
[C:1]([NH:5][C:6]([C@@H:8]1[CH2:17][C@H:16]2[C@H:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[CH2:10][NH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:18][NH2:19]>C(O)C>[NH2:19][C@@H:18]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C@H:6]([OH:7])[CH2:8][N:9]1[C@H:8]([C:6]([NH:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:17][C@H:16]2[C@H:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[CH2:10]1

Participants

4

Reactant 2

HCID 6329MethylamineHCID 454736(3S,4aS,8aS)-N-(tert-Butyl)decahydroisoquinoline-3-carboxamide

Product 1

HCID 9865804(3S,4aS,8aS)-2-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N-tert-butyldecahydroisoquinoline-3-carboxamide

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

(A)(ii) A suspension of 26.55 g of N-tert.butyl-2-[2(R)-hydroxy-4-phenyl-3(S)-phthalimidobutyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide (prepared as described in Example 1) in 100 ml of ethanol was treated with 25 ml of a 30% solution of methylamine in ethanol at room temperature for 1 hour. The mixture was evaporated to dryness under reduced pressure. The residue was dissolved in 250 ml of ethanol, treated with 250 ml of a saturated solution of hydrogen chloride in ethyl acetate and stirred at room temperature for 16 hours. The mixture was evaporated to dryness and the residue was partitioned between ethyl acetate and water. The aqueous phase was separated, made basic with solid sodium carbonate and then extracted with dichloromethane. The dichloromethane extract was washed with sodium chloride solution and evaporated to dryness. The residue was triturated with diethyl ether and, after filtration, there were obtained 17.48 g of 2-[3(S)-amino-2(R)-hydroxy-4-phenylbutyl]-N-tert.butyl-decahydro-(4aS,8aS)-isoquinoline-3(S)-carboxamide as a white solid; MS: m/e 402 [M+H]+.

Workup

  1. customThe mixture was evaporated to dryness under reduced pressure
  2. dissolutionThe residue was dissolved in 250 ml of ethanol
  3. additiontreated with 250 ml of a saturated solution of hydrogen chloride in ethyl acetate
  4. customThe mixture was evaporated to dryness
  5. customthe residue was partitioned between ethyl acetate and water
  6. customThe aqueous phase was separated
  7. extractionextracted with dichloromethane
  8. extractionThe dichloromethane extract
  9. washwas washed with sodium chloride solution
  10. customevaporated to dryness
  11. customThe residue was triturated with diethyl ether
  12. filtrationafter filtration

Sources & evidence

ORD record
ord-d4915910a089411ca4256da9c1cc498f
Source dataset
uspto-grants-1996_01
Patent number
US05488115

Reaction notes

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