Dimethylacetamide → Tert-butyl 4-(3-((tert-butoxycarbonyl)amino)-2-chloro-5-cyanophenyl)piperidine-1-carboxylate

HRID 921661Notes

Reaction equation

HRID 921661 reaction equation
Br[C:2]1[C:3]([Cl:18])=[C:4]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=1.[CH3:19][N:20]([CH3:24])[C:21](=[O:23])C>[Cu]I>[C:13]([O:12][C:11]([NH:10][C:4]1[C:3]([Cl:18])=[C:2]([CH:2]2[CH2:3][CH2:24][N:20]([C:21]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:23])[CH2:19][CH2:7]2)[CH:7]=[C:6]([C:8]#[N:9])[CH:5]=1)=[O:17])([CH3:16])([CH3:15])[CH3:14]

Participants

4

Reactant 2

HCID 31374DimethylacetamideHCID 86708481Tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate

Product 1

HCID 89920397Tert-butyl 4-(3-((tert-butoxycarbonyl)amino)-2-chloro-5-cyanophenyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Conditions

Temperature
80 °C

Procedure

A mixture of tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate (1.0 g, 3.02 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(I) (0.206 g, 0.302 mmol), and copper(I) iodide (0.115 g, 0.603 mmol) in a dry microwave vial was flushed with nitrogen. N,N-dimethylacetamide (3 mL) was added followed by (1-(tert-butoxycarbonyl)piperidin-4-yl)zinc(II) iodide (9.52 mL, 9.05 mmol, approximately 1 M solution in N,N-dimethylacetamide prepared as described in the Journal of Organic Chemistry, 2004, 69, 5120). The vial was sealed and heated at 80° C. overnight. After cooling to room temperature, the reaction was partitioned between EtOAc and sat. aq. NH4Cl solution. This was left stirring for 30 min. The aqueous phase was washed with EtOAc and the combined organic phases were washed with brine and dried with sodium sulfate. Removal of the solvents followed by radial silica gel chromatography eluting with hexane containing 5 to 30% EtOAc afforded tert-butyl 4-(3-((tert-butoxycarbonyl)amino)-2-chloro-5-cyanophenyl)piperidine-1-carboxylate (0.376 g) as a white solid.

Workup

  1. customwas flushed with nitrogen
  2. additionN,N-dimethylacetamide (3 mL) was added
  3. customprepared
  4. customThe vial was sealed
  5. temperatureAfter cooling to room temperature
  6. customthe reaction was partitioned between EtOAc and sat. aq. NH4Cl solution
  7. waitThis was left
  8. washThe aqueous phase was washed with EtOAc
  9. washthe combined organic phases were washed with brine
  10. dry with materialdried with sodium sulfate
  11. customRemoval of the solvents
  12. washeluting with hexane containing 5 to 30% EtOAc

Sources & evidence

ORD record
ord-03046858fa104d81a9723121f4bdb2e3
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

Loading…