Sulfuric Acid → 2-[3(S)-azido-2(R)-hydroxy-4-phenylbutyl]-N-tert.butyl-decahydro-(4aS,8aS)-isoquinoline-3(S)-carboxamide

HRID 440113Notes

Reaction equation

HRID 440113 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].[N:18]([C@H:21]([C@H:29]1[CH2:33]OS(=O)(=O)[O:30]1)[CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[N+:19]=[N-:20].S(=O)(=O)(O)O.[OH-].[Na+]>O1CCCC1.CO>[N:18]([C@@H:21]([CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C@H:29]([OH:30])[CH2:33][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)=[N+:19]=[N-:20]

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 454736(3S,4aS,8aS)-N-(tert-Butyl)decahydroisoquinoline-3-carboxamideHCID 104682854(S)-[1(S)-azido-2-phenylethyl]-1,3,2-dioxathiolane 2,2-dioxide

Product 1

HCID 100712032-[3(S)-azido-2(R)-hydroxy-4-phenylbutyl]-N-tert.butyl-decahydro-(4aS,8aS)-isoquinoline-3(S)-carboxamideYield 13.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 237 mg (1 mmol) of N-tert.butyl-decahydro-(4aS,8aS)-isoquinoline-3(S)-carboxamide and 300 mg (1.1 mmol) of 4(S)-[1(S)-azido-2-phenylethyl]-1,3,2-dioxathiolane 2.2-dioxide in 10 ml of tetrahydrofuran was stirred at room temperature under an argon atmosphere for 2 days, during which time some white solid deposits formed. The mixture was evaporated to give a white powder which was taken up in a 10% solution of sulphuric acid in 70% aqueous methanol and heated under reflux for 30 minutes. After cooling to room temperature the solution was adjusted to pH 10 with 10% aqueous sodium hydroxide solution and extracted three times with ethyl acetate. The ethyl acetate extracts were combined, washed with sodium chloride solution, dried over anhydrous magnesium sulphate and evaporated. Purification of the crude product by flash chromatography on silica gel using n-hexane/ethyl acetate (4:1) for the elution gave 57 mg of 2-[3(S)-azido-2(R)-hydroxy-4-phenylbutyl]-N-tert.butyl-decahydro-(4aS,8aS)-isoquinoline-3(S)-carboxamide; MS: m/e 428 [M+H]+.

Workup

  1. customformed
  2. customThe mixture was evaporated
  3. customto give a white powder which
  4. temperatureheated
  5. temperatureunder reflux for 30 minutes
  6. extractionextracted three times with ethyl acetate
  7. washwashed with sodium chloride solution
  8. dry with materialdried over anhydrous magnesium sulphate
  9. customevaporated
  10. customPurification of the crude product by flash chromatography on silica gel
  11. washfor the elution

Sources & evidence

ORD record
ord-33c09f2abbd14138853b71de001907d8
Source dataset
uspto-grants-1996_05
Patent number
US05516913

Reaction notes

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