Hydrochloric Acid → HCID 178483323, compound

HRID 1295365Notes

Reaction equation

HRID 1295365 reaction equation
[F:1][C:2]([F:28])([F:27])[C:3]1[CH:4]=[C:5]([CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:22]=1)[CH2:6][O:7][C@@:8]12[CH2:13][CH:12]1[CH2:11][NH:10][C@H:9]2[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[CH3:29][N:30]([CH2:32][C:33]1[NH:37][N:36]=[N:35][C:34]=1[CH:38]=O)[CH3:31].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl.[OH-].[Na+].C(=O)(O)[O-].[Na+]>COCCOC>[F:28][C:2]([F:1])([F:27])[C:3]1[CH:4]=[C:5]([CH:20]=[C:21]([C:23]([F:26])([F:24])[F:25])[CH:22]=1)[CH2:6][O:7][C@@:8]12[CH2:13][CH:12]1[CH2:11][N:10]([CH2:38][C:34]1[N:35]=[N:36][NH:37][C:33]=1[CH2:32][N:30]([CH3:31])[CH3:29])[C@H:9]2[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 86602051(1S,2S)-1-(3,5-bis-trifluoromethyl-benzyloxy)-2-phenyl-3-aza-bicyclo[3.1.0]hexaneHCID 178483326HCID 178483326, compound

Product 1

HCID 178483323HCID 178483323, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

To the starting material as a mixture of diastereomers, Example 6 and Example 7, one being (1S,2S)-1-(3,5-bis-trifluoromethyl-benzyloxy)-2-phenyl-3-aza-bicyclo[3.1.0]hexane, (0.10 g, 0.25 mmol) in DME (1.0 mL) was added 5-dimethylaminomethyl-1H-[1,2,3]triazole-4-carbaldehyde (˜50% pure, 0.15 g, 0.45 mmol) mmol and the mixture stirred at room temperature for 1.5 hours. To the reaction flask was added sodium triacetoxyborohydride (0.10 g, 0.50 mmol) and stirring was continued for 64 hours. The reaction flask was placed in a 0° C. bath and to the reaction flask was added 1N HCl (2 mL) and the mixture stirred for 4 hours at room temperature. 1 N NaOH solution was added 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 to an oil. The crude product was purified by flash chromatography using elution with a gradient of 30% EtOAc/Hexanes to 100% EtOAc to give as the more polar diastereomer of the title compound. (0.034 g, 25% yield).).

Workup

  1. stirringstirring
  2. waitwas continued for 64 hours
  3. customwas placed in a 0° C.
  4. stirringthe mixture stirred for 4 hours at room temperature
  5. extractionThe reaction mixture was extracted with methylene chloride
  6. washthe organics washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to an oil
  10. customThe crude product was purified by flash chromatography
  11. washelution with a gradient of 30% EtOAc/Hexanes to 100% EtOAc

Sources & evidence

ORD record
ord-4495a266a11d4629a303e65be35f63a8
Source dataset
uspto-grants-2007_07
Patent number
US07241798B2

Reaction notes

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