Acetonitrile → HCID 14457608, compound

HRID 1195012Notes

Reaction equation

HRID 1195012 reaction equation
[F:1][C:2]([F:12])([F:11])[C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[CH2:6]Cl.[CH3:13][O:14][C:15]([CH:17]1[N:22]([C:23](=[O:37])[CH:24]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:21][C:20]2[N:38](CC(=O)C3C=CC=CC=3)[CH2:39][NH:40][C:19]=2[CH2:18]1)=[O:16].C(#N)C>CCOCC>[CH3:13][O:14][C:15]([CH:17]1[N:22]([C:23](=[O:37])[CH:24]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH2:21][C:20]2[N:38]=[CH:39][N:40]([CH2:6][C:5]3[CH:8]=[CH:9][CH:10]=[C:3]([C:2]([F:12])([F:11])[F:1])[CH:4]=3)[C:19]=2[CH2:18]1)=[O:16]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 697163-(Trifluoromethyl)benzyl chloride2×HCID 21249260HCID 21249260, compound

Product 1

HCID 14457608HCID 14457608, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

A solution of 1.4 g 3-trifluoromethylbenzyl chloride, 3.0 g methyl-5-diphenylacetyl-3-(2-oxo-2-phenylethyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylate and 20 mL acetonitrile is heated at reflux 16 hr. An additional 1.4 mL 3-trifluoromethylbenzyl chloride is added and refluxing continued 24 hr. The cooled solution is added dropwise to 400 mL vigorously stirred ether and the resulting precipitate is collected by filtration. This precipitate is dissolved in 60 mL methanol and treated with 10 g zinc dust and 60 mL acetic acid. The resulting suspension is sonicated 2 hr then the solution is filtered from excess zinc. The filtrate is dissolved in 400 mL dichloromethane and treated dropwise with 520 mL 10% Na2CO3 with vigorous stirring. The organic phase is separated, dried, concentrated and the major product is isolated by chromatography on silica gel (chloroform-methanol, 99.5:0.5) as a crisp foam. NMR (CDCl3) 5.05 (s, 2H, NCH2Ar).

Workup

  1. temperatureat reflux 16 hr
  2. temperaturerefluxing continued 24 hr
  3. filtrationthe resulting precipitate is collected by filtration
  4. dissolutionThis precipitate is dissolved in 60 mL methanol
  5. additiontreated with 10 g zinc dust and 60 mL acetic acid
  6. customThe resulting suspension is sonicated 2 hr
  7. filtrationthe solution is filtered from excess zinc
  8. dissolutionThe filtrate is dissolved in 400 mL dichloromethane
  9. additiontreated dropwise with 520 mL 10% Na2CO3 with vigorous stirring
  10. customThe organic phase is separated
  11. customdried
  12. concentrationconcentrated
  13. customthe major product is isolated by chromatography on silica gel (chloroform-methanol, 99.5:0.5) as a crisp foam

Sources & evidence

ORD record
ord-74d244e1bb7a45efa6d5b52ed9e97fac
Source dataset
uspto-grants-1989_03
Patent number
US04816463

Reaction notes

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