Diethyl Ether → HCID 22612692, compound

HRID 844104Notes

Reaction equation

HRID 844104 reaction equation
[F:1][C:2]([F:30])([F:29])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][C:13]([CH:16]3[CH2:20][NH:19][C:18]([C:21]4[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=4[F:28])=[N:17]3)=[CH:12][CH:11]=2)=[CH:6][CH:5]=1.C(N(CC)CC)C.[CH2:38]([O:40][CH2:41]Cl)[CH3:39].[CH3:43][CH2:44][O:45][CH2:46]C>ClCCl>[CH2:38]([O:40][CH2:41][N:19]1[CH2:20][CH:16]([C:13]2[CH:12]=[CH:11][C:10]([C:7]3[CH:8]=[CH:9][C:4]([O:3][C:2]([F:1])([F:29])[F:30])=[CH:5][CH:6]=3)=[CH:15][CH:14]=2)[N:17]=[C:18]1[C:21]1[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=1[F:28])[CH3:39].[CH2:44]([O:45][CH2:46][N:17]1[CH:16]([C:13]2[CH:12]=[CH:11][C:10]([C:7]3[CH:8]=[CH:9][C:4]([O:3][C:2]([F:1])([F:29])[F:30])=[CH:5][CH:6]=3)=[CH:15][CH:14]=2)[CH2:20][N:19]=[C:18]1[C:21]1[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=1[F:28])[CH3:43]

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 8471Triethylamine3×HCID 18523Chloromethyl ethyl etherHCID 178505722HCID 178505722, compound

Product 2

HCID 22612686HCID 22612686, compoundYield 17%HCID 22612692HCID 22612692, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

At 0° C., a solution of 1.5 g (3.6 mmol) of 4-(4′-trifluoromethoxy-4-biphenylyl)-2-(2,6-difluorophenyl)-4,5-dihydro-1H-imidazole (for example from Example V-1) in 15 ml of dichloromethane was admixed first with 0.75 ml (0.55 g; 5.4 mmol) of triethylamine and then with 4 ml (0.41 g; 4.32 mmol) of chloromethyl ethyl ether. After the mixture had been stirred overnight, approximately 50% of starting material were still present (TLC). A further 0.25 ml of triethylamine and 0.17 ml of the ether were introduced. Since no further reaction could be detected, another 0.25 ml of triethylamine was added and the mixture was heated to the boil. For work-up, the reaction mixture was extracted with 10% strength citric acid and 1N aqueous sodium hydroxide solution, dried, concentrated and chromatographed over a silica gel column (Ø=3 cm, 1=30 cm). Elution with cyclohexane/ethyl acetate using a 5-stage gradient from 20:1 to 3:1 gave, as second fraction, 0.30 g (17% of theory) of 1-ethoxymethyl-4-(4′-trifluoromethoxy-4-biphenylyl)-2-(2,6-difluorophenyl)-4,5-di-hydro-1H-imidazole (I-6a) and, as third fraction, 0.34 g (20% of theory) of 3-ethoxymethyl-4-(4′-trifluoromethoxy-4-biphenylyl)-2-(2,6-difluorophenyl)-4,5-di-hydro-3H-imidazole (I-6b).

Workup

  1. customAt 0° C.
  2. customSince no further reaction
  3. temperaturethe mixture was heated to the boil
  4. extractionFor work-up, the reaction mixture was extracted with 10% strength citric acid and 1N aqueous sodium hydroxide solution
  5. customdried
  6. concentrationconcentrated
  7. customchromatographed over a silica gel column (Ø=3 cm, 1=30 cm)
  8. washElution with cyclohexane/ethyl acetate using a 5-stage gradient from 20:1 to 3:1

Sources & evidence

ORD record
ord-6f173d7ba27142b883f04daaf5e5913b
Source dataset
uspto-grants-2002_04
Patent number
US06380237B1

Reaction notes

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