1,4-Dibromobutane → cis-(2-Pyrrolidin-1-yl-cyclohexyl)-carbamic acid tert-butyl ester

HRID 1950895

Reaction equation

HRID 1950895 reaction equation
[CH3:1][C:2]([O:5][C:6]([NH:8][C@@H:9]1[C@H:14]([NH2:15])[CH2:13][CH2:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])[CH3:3].C(=O)([O-])[O-].[K+].[K+].Br[CH2:23][CH2:24][CH2:25][CH2:26]Br>C(#N)C>[C:2]([O:5][C:6](=[O:7])[NH:8][C@@H:9]1[CH2:10][CH2:11][CH2:12][CH2:13][C@@H:14]1[N:15]1[CH2:26][CH2:25][CH2:24][CH2:23]1)([CH3:1])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 80561,4-DibromobutaneHCID 11430Potassium CarbonateHCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected

Product 1

HCID 66680888cis-(2-Pyrrolidin-1-yl-cyclohexyl)-carbamic acid tert-butyl esterYield 88.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1-N-Boc-1,2-cis-cyclohexyldiamine 5 (CAS 184954-75-4) (1.65 g, 7.7 mmol) was dissolved in 100 mL acetonitrile. Potassium carbonate (5.3 g, 39 mmol) and 1,4-dibromobutane (2.8 g, 13 mmol) were added and the reaction mixture was refluxed overnight. The solvent was evaporated off. The residue was taken up in water and ethyl acetate and was extracted three times with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on silica gel (dichloromethane/methanol/ammonia 100:0:0->140:10:1) yielded cis-(2-pyrrolidin-1-yl-cyclohexyl)-carbamic acid tert-butyl ester as a yellow liquid (1.82 g, 88%), MS: m/e=269.4 [(M+H)+].

Workup

  1. temperaturethe reaction mixture was refluxed overnight
  2. customThe solvent was evaporated off
  3. extractionethyl acetate and was extracted three times with ethyl acetate
  4. customThe combined organic phases were dried on sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customPurification of the residue by flash chromatography on silica gel (dichloromethane/methanol/ammonia 100:0:0->140:10:1)

Sources & evidence

ORD record
ord-5e0e1221301f4894b1529479b925d73b
Source dataset
uspto-grants-2013_03
Patent number
US08404673B2

Linked notes

Loading…