HCID 20147712, compound → HCID 20147694, compound

HRID 569585Notes

Reaction equation

HRID 569585 reaction equation
C([Li])CCC.[Cl:6][C:7]1[CH:12]=[C:11]([Cl:13])[CH:10]=[CH:9][C:8]=1[N:14]1[CH2:18][CH2:17][N:16]=[C:15]1[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[N:26]1([CH2:31][CH2:32]OS(C2C(C)=CC=CC=2)(=O)=O)[CH:30]=[CH:29][N:28]=[CH:27]1>O1CCCC1>[Cl:6][C:7]1[CH:12]=[C:11]([Cl:13])[CH:10]=[CH:9][C:8]=1[N:14]1[CH2:18][CH2:17][N:16]=[C:15]1[CH:19]([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[CH2:32][CH2:31][N:26]1[CH:30]=[CH:29][N:28]=[CH:27]1

Participants

5

Reactant 3

HCID 20147712HCID 20147712, compoundHCID 86741463HCID 86741463, compoundHCID 178418339Butyllithium

Product 1

HCID 20147694HCID 20147694, compoundYield 51.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1-(2,4-Dichlorophenyl)-4,5-dihydro-2-[3-(imidazol-1-yl)-1-phenylpropyl]imidazole To a stirred solution of 2-(imidazol-1-yl)ethanol (1.9 g, 0.0156 mol), triethylamine (2.8 ml, 0.0187 mol), and 4-N,N-dimethylaminopyridine (20 mg) in dichloromethane (20 ml) at a temperature of -78° C. under nitrogen atmosphere, was added p-toluenesulphonyl chloride (3.6 g, 0.0187 mol) in dichloromethane (10 ml). The reaction mixture was allowed to warm to -10° C. and was then quenched by the addition of saturated aqueous sodium hydrogen carbonate. The organic phase was separated and the aqueous phase extracted with dichloromethane. The organic phases were combined, washed with brine, dried over anhydrous magnesium sulphate and concentrated under reduced pressure to yield colorless crystals of 2-(imidazol-1-yl)-1-toluenesulphonyloxyethane (4.23 g). n-Butyllithium (3.9 ml, 0.0059 mol, 1.5M in hexane) was added to a stirred solution of 1-(2,4-dichlorophenyl)-4,5-dihydro-2-phenylmethylimidazole (1.5 g, 0.0049 mol) in dry tetrahydrofuran (10 ml) at -78° C. under a nitrogen atmosphere. Copper(I)bromide-dimethyl sulphide complex (50 mg, 0.0024 mol) was added to the reaction mixture. After a period of one hour, a solution of 2-(imidazol-1-yl)-1-toluenesulphonyloxyethane (2 g, 0.0072 mol) in tetrahydrofuran (7 ml) was added to the reaction mixture. The resulting mixture was allowed to warm to room temperature and allowed to react for 15 hours before being quenched with saturated aqueous ammonium chloride. The phases were separated and the aqueous phase extracted with ethyl acetate. The organic phases were combined, washed with brine, dried over anhydrous magnesium sulphate and concentrated under reduced pressure to yield an oil which was chromatographed on silica gel with ammonia/methanol/ethyl acetate (1:4:45) to yield 1-(2,4-dichlorophenyl)-4,5-dihydro-2-[3-(imidazol-1-yl)-1-phenylpropyl]imidazole (1 g) which upon treatment with ethereal hydrogen chloride yielded the hydrochloride salt of 1-(2,4-dichlorophenyl)-4,5-dihydro-2-[3-(imidazol-1-yl)-1-phenylpropyl]imidazole. (Found C, 49.00; H, 5.03; N, 10.76. C21H22N4Cl4.9/4H2O requires C, 49.19; H, 5.21; N, 10.93) having the formula ##STR43##

Workup

  1. additionCopper(I)bromide-dimethyl sulphide complex (50 mg, 0.0024 mol) was added to the reaction mixture
  2. customto react for 15 hours
  3. custombefore being quenched with saturated aqueous ammonium chloride
  4. customThe phases were separated
  5. extractionthe aqueous phase extracted with ethyl acetate
  6. washwashed with brine
  7. dry with materialdried over anhydrous magnesium sulphate
  8. concentrationconcentrated under reduced pressure
  9. customto yield an oil which
  10. customwas chromatographed on silica gel with ammonia/methanol/ethyl acetate (1:4:45)

Sources & evidence

ORD record
ord-9389ac03e48746c4a784f01ebce8a26b
Source dataset
uspto-grants-1988_03
Patent number
US04732989

Reaction notes

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