Triethylamine → 3-(3,3-Dimethylbutyl)-3-azabicyclo[3.1.0]hexane-6-carboxamide

HRID 340744Notes

Reaction equation

HRID 340744 reaction equation
Cl.[CH:2]12[CH:7]([C:8]([NH2:10])=[O:9])[CH:6]1[CH2:5][NH:4][CH2:3]2.C(N(CC)CC)C.[CH3:18][C:19]([CH3:24])([CH3:23])[CH2:20][CH:21]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.CO>[CH3:18][C:19]([CH3:24])([CH3:23])[CH2:20][CH2:21][N:4]1[CH2:5][CH:6]2[CH:2]([CH:7]2[C:8]([NH2:10])=[O:9])[CH2:3]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 763353,3-DimethylbutanalHCID 5049666Sodium triacetoxyborohydrideHCID 1177007423-Azabicyclo[3.1.0]hexane-6-carboxamide HCl

Product 1

HCID 1177004863-(3,3-Dimethylbutyl)-3-azabicyclo[3.1.0]hexane-6-carboxamideYield 79.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent4×

Procedure

The 3-azabicyclo[3.1.0]hexane-6-carboxamide hydrochloride (169 mg, 1.04 mmol) prepared in Example 5 and a molecular sieve were dried in vacuum and dissolved in 5 mL of methylene chloride. Then, triethylamine (151 μL, 1.08 mmol) was added dropwise at 0° C. After adding 3,3-dimethylbutyraldehyde (135 μL, 1.08 mmol), the mixture was stirred at room temperature for 1 hour. After adding sodium triacetoxyborohydride (687 mg, 3.24 mmol) and then adding 10 mL of methylene chloride, the mixture was stirred for 2 hours and 30 minutes. The completion of the reaction was confirmed by TLC (CH2Cl2:MeOH=10:1). After the reaction was completed, the reaction mixture was diluted with methylene chloride and extracted several times with saturated sodium bicarbonate. The organic layer was dried with anhydrous magnesium sulfate, filtered, concentrated under reduced pressure and separated by column chromatography (CH2Cl2:MeOH=10:1) to obtain 173 mg (79.2%) of the target compound.

Workup

  1. stirringthe mixture was stirred for 2 hours and 30 minutes
  2. extractionextracted several times with saturated sodium bicarbonate
  3. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customseparated by column chromatography (CH2Cl2:MeOH=10:1)

Sources & evidence

ORD record
ord-001973dcef4d4cb8a5203363ccb32b83
Source dataset
uspto-grants-2014_11
Patent number
US08895602B1

Reaction notes

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