Ammonia → Methyl-(2-phenyl-3-aza-bicyclo[3.1.0]hex-1-yl)-carbamic acid tert-butyl ester

HRID 1295354Notes

Reaction equation

HRID 1295354 reaction equation
[Na].N.[C:3]([O:7][C:8](=[O:33])[N:9]([CH3:32])[C:10]12[CH2:15][CH:14]1[CH2:13][N:12](S(C1C=CC(C)=CC=1)(=O)=O)[CH:11]2[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)([CH3:6])([CH3:5])[CH3:4].[Cl-].[NH4+]>C1COCC1>[C:3]([O:7][C:8](=[O:33])[N:9]([CH3:32])[C:10]12[CH2:15][CH:14]1[CH2:13][NH:12][CH:11]2[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)([CH3:6])([CH3:5])[CH3:4]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 25517Ammonium ChlorideHCID 5360545SodiumHCID 69336275Methyl-[2-phenyl-3-(toluene-4-sulfonyl)-3-aza-bicyclo[3.1.0]hex-1-yl]-carbamic acid tert-butyl ester2×

Product 1

HCID 69336685Methyl-(2-phenyl-3-aza-bicyclo[3.1.0]hex-1-yl)-carbamic acid tert-butyl esterYield 99.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a flame dried 125 mL rbf equipped with a dry ice condenser was added fresh sodium metal (0.32 g, 14.0 mmol). The flask was immersed in a −78° C. bath and ammonia gas was condensed into the flask until it was about a third full. The starting material methyl-[2-phenyl-3-(toluene-4-sulfonyl)-3-aza-bicyclo[3.1.0]hex-1-yl]-carbamic acid tert-butyl ester (Intermediate 9) (0.62 g, 1.40 mmol) in THF (10 mL) was added to the flask in a thin constant stream and the mixture was stirred for 10 minutes at which point tlc indicated the reaction was complete. Solid ammonium chloride was added cautiously and the reaction warmed to room temperature. The volatile solvents were allowed to evaporate and the residue was partitioned between 1N NaOH and methylene chloride. The organics were washed with brine, dried over sodium sulfate, filtered, and concentrated to give methyl-(2-phenyl-3-aza-bicyclo[3.1.0]hex-1-yl)-carbamic acid tert-butyl ester as an oil (0.40 g, quantitative yield).

Workup

  1. customTo a flame dried 125 mL
  2. customrbf equipped with a dry ice condenser
  3. customwas immersed in a −78° C.
  4. customcondensed into the flask until it
  5. customto evaporate
  6. customthe residue was partitioned between 1N NaOH and methylene chloride
  7. washThe organics were washed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-6c14670e0dfe4edea364017a0cad9233
Source dataset
uspto-grants-2007_07
Patent number
US07241798B2

Reaction notes

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