Phenyl thioxochloroformate → 4-(2-Methyl-5,6,7,8-tetrahydro-quinolin-7-ylmethyl)-1,3-dihydro-imidazole-2-thione

HRID 2099435Notes

Reaction equation

HRID 2099435 reaction equation
[NH:1]1[CH:5]=[C:4]([CH2:6][CH:7]2[CH2:16][C:15]3[N:14]=[C:13]([CH3:17])[CH:12]=[CH:11][C:10]=3[CH2:9][CH2:8]2)[N:3]=[CH:2]1.C([O-])(O)=O.[Na+].C1C=CC(OC(Cl)=[S:31])=CC=1>C1COCC1.O>[CH3:17][C:13]1[CH:12]=[CH:11][C:10]2[CH2:9][CH2:8][CH:7]([CH2:6][C:4]3[NH:3][C:2](=[S:31])[NH:1][CH:5]=3)[CH2:16][C:15]=2[N:14]=1

Participants

6

Reactant 3

HCID 70498Phenyl thioxochloroformateHCID 516892Sodium BicarbonateHCID 178422884HCID 178422884, compound2×

Product 1

HCID 112424024-(2-Methyl-5,6,7,8-tetrahydro-quinolin-7-ylmethyl)-1,3-dihydro-imidazole-2-thione

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 7-(1H-imidazol-4-ylmethyl)-2-methyl-5,6,7,8-tetrahydro-quinoline (Intermediate 200A5) (5.16 g, 22.7 mmol) in THF (20 mL) and water (20 mL) was treated with NaHCO3 (11.5 g, 136 mmol) and phenyl chlorothionoformate (7.9 mL, 57 mmol). Stirring was continued for 5 h at rt. The mixture was diluted with water and extracted with ethyl acetate (2×). The organic portions were combined, dried over MgSO4, filtered and freed of solvent. The residue was dissolved in MeOH (10 mL) and treated with NEt3 (140 mL) for 18 h. The mixture was evaporated to dryness, diluted with water and extracted with chloroform:isopropanol (3:1). The organic portions were combined, dried over MgSO4, filtered and concentrated onto SiO2. The solvent was removed under vacuum and the product was purified on a column of SiO2 with a gradient elution of 60% acetone:hexanes to 100% acetone to give enantiomeric 4-(2-methyl-5,6,7,8-tetrahydro-quinolin-7-ylmethyl)-1,3-dihydro-imidazole-2-thione (Compound 201, racemic mixture) as a white solid, 3.0 g (51%). Individual enantiomers can be obtained from the racemic mixture as described below.

Workup

  1. extractionextracted with ethyl acetate (2×)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. dissolutionThe residue was dissolved in MeOH (10 mL)
  5. additiontreated with NEt3 (140 mL) for 18 h
  6. customThe mixture was evaporated to dryness
  7. additiondiluted with water
  8. extractionextracted with chloroform:isopropanol (3:1)
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated onto SiO2
  12. customThe solvent was removed under vacuum
  13. customthe product was purified on a column of SiO2 with a gradient elution of 60% acetone

Sources & evidence

ORD record
ord-550db280b36a4fe5bddbeeea77e54cde
Source dataset
uspto-grants-2009_08
Patent number
US07569584B2

Reaction notes

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