Phosgene → 1,1-Dimethylethyl 4-(6-chloro-5-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-piperidinecarboxylate

HRID 2064126Notes

Reaction equation

HRID 2064126 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([Cl:9])=[CH:4][C:3]=1[NH:10][CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1.[C:24](Cl)(Cl)=[O:25].C(N(CC)CC)C>ClCCl.C1(C)C=CC=CC=1>[Cl:9][C:5]1[C:6]([CH3:8])=[CH:7][C:2]2[NH:1][C:24](=[O:25])[N:10]([CH:11]3[CH2:12][CH2:13][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:15][CH2:16]3)[C:3]=2[CH:4]=1

Participants

6

Reactant 3

HCID 6371PhosgeneHCID 8471TriethylamineHCID 598502121,1-Dimethylethyl 4-[(2-amino-5-chloro-4-methylphenyl)amino]-1-piperidinecarboxylate

Product 1

HCID 598501761,1-Dimethylethyl 4-(6-chloro-5-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-piperidinecarboxylate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

1,1-Dimethylethyl 4-[(2-amino-5-chloro-4-methylphenyl)amino]-1-piperidinecarboxylate (D7) (0.292 mmol, 100 mg) was dissolved in 10 ml of dichloromethane and a 20% solution in toluene of phosgene (1.05 eq., 150 microliters) followed by triethylamine (2.1 eq., 85 microliters) were added at 0° C.; the reaction mixture was then stirred at 0° C. for 30 minutes and subsequently quenched with citric acid (10% aqueous solution). The reaction mixture was diluted with dichloromethane, the two phases were separated and the aqueous phase was extracted with dichloromethane (1×); the organic phases were combined, dried over Na2SO4, filtered and the solvent was evaporated to afford the crude compound that was purified by chromatography (ethyl acetate-hexane) to yield the title compound, 50 mg, 50%, M+−H=364.

Workup

  1. additionwere added at 0° C.
  2. customsubsequently quenched with citric acid (10% aqueous solution)
  3. additionThe reaction mixture was diluted with dichloromethane
  4. customthe two phases were separated
  5. extractionthe aqueous phase was extracted with dichloromethane (1×)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customthe solvent was evaporated
  9. customto afford the crude compound that
  10. customwas purified by chromatography (ethyl acetate-hexane)

Sources & evidence

ORD record
ord-44894e5a60084e3281a290de212dc33a
Source dataset
uspto-grants-2012_10
Patent number
US08288412B2

Reaction notes

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