Benzylamine → 1-(4-Benzylamino-phenyl)-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester

HRID 1400021Notes

Reaction equation

HRID 1400021 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]2[C:10]([C:14]3[CH:19]=[CH:18][C:17](Br)=[CH:16][CH:15]=3)([CH2:11]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[Na+].[CH2:27]([NH2:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]2[C:10]([C:14]3[CH:19]=[CH:18][C:17]([NH:34][CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[CH:16][CH:15]=3)([CH2:11]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 7504BenzylamineHCID 23676156Sodium t-butoxideHCID 53432548tert-Butyl 1-(4-bromophenyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate2×

Product 1

HCID 675083621-(4-Benzylamino-phenyl)-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl esterYield 80%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

To a solution of 1-(4-bromo-phenyl)-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester (Intermediate I, 3.5 g, 10.4 mmol) in toluene (20 mL) were added Pd2(dba)3 (47 mg, 0.05 mmol), BINAP (97 mg, 0.16 mmol), sodium tert-butoxide (2.0 g, 20.7 mmol) and benzyl amine (1.2 mL, 11.4 mmol). The resulting solution was refluxed for 4 h. After the completion of the reaction, the reaction mixture was adsorbed on silica gel and purified by column chromatography (silica gel, 4:6 EtOAc:Pet. ether) to yield the title compound (3.0 g, 80%) as yellow solid.

Workup

  1. temperatureThe resulting solution was refluxed for 4 h
  2. customAfter the completion of the reaction
  3. custompurified by column chromatography (silica gel, 4:6 EtOAc:Pet. ether)

Sources & evidence

ORD record
ord-737b4ea47f8f4fe7a36d0aa58b63c04b
Source dataset
uspto-grants-2014_12
Patent number
US08906913B2

Reaction notes

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