Ammonia → tert-Butyl 6-carbamoyl-3-azabicyclo[3.1.0]hexane-3-carboxylate

HRID 340742Notes

Reaction equation

HRID 340742 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]2[CH:10]([CH:11]2[C:14]([OH:16])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:17]1C2C=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C.C(N(C(C)C)CC)(C)C.N>C(Cl)Cl.CO>[C:14]([CH:11]1[CH:12]2[CH:10]1[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:13]2)(=[O:16])[NH2:17]

Participants

8

Reactant 5

HCID 222AmmoniaHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 533952883-((Tert-butoxy)carbonyl)-3-azabicyclo(3.1.0)hexane-6-carboxylic acidHCID 178418385HCID 178418385, compound

Product 1

HCID 70222027tert-Butyl 6-carbamoyl-3-azabicyclo[3.1.0]hexane-3-carboxylateYield 70.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent3×

Procedure

The 3-(tert-butoxycarbonyl)-3-azabicyclo[3.1.0]hexane-6-carboxylic acid (252 mg, 1.11 mmol) prepared in Example 3, benzotriazole (180 mg, 1.33 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (255 mg, 1.33 mmol) were dissolved in 3.0 mL of methylene chloride and diisopropylethylamine (232 μL, 1.33 mmol) was added dropwise. After adding 2 M ammonia solution (2.49 mL, 4.98 mmol) dissolved in methanol dropwise at 0° C., the mixture was stirred at room temperature for 4 hours. The completion of the reaction was confirmed by TLC (CH2Cl2:MeOH=15:1). After the reaction was completed, the reaction mixture was diluted with methylene chloride and washed with saturated sodium chloride. The organic layer was dried with anhydrous magnesium sulfate, filtered, concentrated under reduced pressure and separated by column chromatography (CH2Cl2:MeOH=15:1) to obtain 177 mg (70.6%) of the target compound.

Workup

  1. washwashed with saturated sodium chloride
  2. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customseparated by column chromatography (CH2Cl2:MeOH=15:1)

Sources & evidence

ORD record
ord-c35230e87fdb4aa1901580654cb8efea
Source dataset
uspto-grants-2014_11
Patent number
US08895602B1

Reaction notes

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