Hydrochloric Acid → HCID 178483321, compound

HRID 1295362Notes

Reaction equation

HRID 1295362 reaction equation
[F:1][C:2]([F:29])([F:28])[C:3]1[CH:4]=[C:5]([CH:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=1)[CH2:6][O:7][CH2:8][C@@:9]12[CH2:14][CH:13]1[CH2:12][NH:11][C@H:10]2[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[CH3:30][N:31]([CH2:33][C:34]1[NH:38][N:37]=[N:36][C:35]=1[CH:39]=O)[CH3:32].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl.[OH-].[Na+].C(=O)(O)[O-].[Na+]>COCCOC>[F:29][C:2]([F:28])([F:1])[C:3]1[CH:4]=[C:5]([CH:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=1)[CH2:6][O:7][CH2:8][C:9]12[CH2:14][CH:13]1[CH2:12][N:11]([CH2:39][C:35]1[N:36]=[N:37][NH:38][C:34]=1[CH2:33][N:31]([CH3:32])[CH3:30])[CH:10]2[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 86602046(1S,2S)-1-(3,5-Bis-trifluoromethyl-benzyloxymethyl)-2-phenyl-3-aza-bicyclo[3.1.0]hexaneHCID 178483326HCID 178483326, compound

Product 1

HCID 178483321HCID 178483321, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

To racemic Intermediate 24, one enantiomer being (1S,2S)-1-(3,5-bis-trifluoromethyl-benzyloxymethyl)-2-phenyl-3-aza-bicyclo[3.1.0]hexane (0.08 g, 0.18 mmol) in DME (1.0 mL) was added 5-dimethylaminomethyl-1H-[1,2,3]triazole-4-carbaldehyde (˜50% pure, 0.14 g, 0.91 mmol) and the mixture stirred at room temperature for 3 hours. To the reaction flask was added sodium triacetoxyborohydride (0.08 g, 0.36 mmol) and stirring was continued for 16 hours. To the reaction flask was added 1 N HCl (2 mL) and the mixture stirred for 2 hours. 1 N NaOH solution was added cautiously and then saturated sodium bicarbonate solution was added until the pH=8. The reaction mixture was extracted with methylene chloride, the organics washed with brine, dried over sodium sulfate, filtered, and concentrated. The crude product was purified by flash chromatography using elution of a gradient of 50% EtOAc/Hexanes to 3% MeOH/EtOAc to give the title compound. (0.065 g, 66% yield).

Workup

  1. stirringstirring
  2. waitwas continued for 16 hours
  3. stirringthe mixture stirred for 2 hours
  4. extractionThe reaction mixture was extracted with methylene chloride
  5. washthe organics washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by flash chromatography
  10. washelution of a gradient of 50% EtOAc/Hexanes to 3% MeOH/EtOAc

Sources & evidence

ORD record
ord-8be32a0854e94a4dab5907a686879e75
Source dataset
uspto-grants-2007_07
Patent number
US07241798B2

Reaction notes

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