N,N,N',N'-Tetramethylethylenediamine → 4,5-Bis(4-methoxyphenyl)-alpha,alpha-di(trifluoromethyl)-1H-imidazole-2-methanamine

HRID 1702663Notes

Reaction equation

HRID 1702663 reaction equation
C(OC([N:6]1[C:10]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)=[C:9]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)[N:8]=[CH:7]1)C)C.CN(C)CCN(C)C.C([Li])CCC.[F:40][C:41]([F:53])([F:52])[C:42](=[N:47][Si](C)(C)C)[C:43]([F:46])([F:45])[F:44].C(=O)(O)[O-].[Na+].COC1C=CC(N2C=CN=C2C(C(F)(F)F)(C(F)(F)F)N)=CC=1>C1COCC1.CCCCCC>[CH3:26][O:25][C:22]1[CH:21]=[CH:20][C:19]([C:9]2[N:8]=[C:7]([C:42]([C:43]([F:46])([F:45])[F:44])([C:41]([F:53])([F:52])[F:40])[NH2:47])[NH:6][C:10]=2[C:11]2[CH:12]=[CH:13][C:14]([O:17][CH3:18])=[CH:15][CH:16]=2)=[CH:24][CH:23]=1

Participants

9

Reactant 6

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 516892Sodium BicarbonateHCID 13274636[1,1-Di(trifluoromethyl)methyleneamino]trimethylsilaneHCID 204060854,5-Bis(4-methoxyphenyl)-1-(alpha-ethoxyethyl)imidazoleHCID 867385664-methoxyphenyl-alpha,alpha-di(trifluoromethyl)-1H-imidazole-2-methanamineHCID 178418339Butyllithium

Product 1

HCID 130505714,5-Bis(4-methoxyphenyl)-alpha,alpha-di(trifluoromethyl)-1H-imidazole-2-methanamine

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

A solution of 10.0 g (28.4 mmoles) of 1-(α-ethoxyethyl)-4,5-bis-(4-methoxyphenyl)-1H-imidazole and 3.9 g of tetramethylethylenediamine in 150 ml THF was cooled to -78° C. with a dry-ice acetone bath, and a solution of 30 ml of of 1.6 M butyl lithium in hexane was then added dropwise. After stirring for 15 minutes, 11.5 g (48.5 mmoles) of [1,1-di(trifluoromethyl)methyleneamino]trimethylsilane [R. F. Swindell et al., Inorganic Chemistry, 11, #2, 242 (1972)] was added dropwise, and the reaction mixture was then allowed to warm to room temperature. A solution of 10% aqueous sodium bicarbonate (100 ml) was added dropwise and the organic layer was separated and concentrated in vacuo. The residue was stirred with a mixture of 200 ml of ethanol and 100 ml 2 M aqueous HCl overnight. The ethanol was evaporated under vacuum and the aqueous phase was extracted with ether. The combined ether extracts were washed with water, dried and concentrated to give 4.6 g (36%) of crude 4,5-bis(4-methoxyphenyl-α,α-di(trifluoromethyl)-1H-imidazole-2-methanamine. The residue was chromatographed on silica gel eluting with chloroform to give, after recrystallization from methylcyclohexane, the product as colorless crystals, m.p. 127°-128.5° C.

Workup

  1. customthe organic layer was separated
  2. concentrationconcentrated in vacuo
  3. stirringThe residue was stirred with a mixture of 200 ml of ethanol and 100 ml 2 M aqueous HCl overnight
  4. customThe ethanol was evaporated under vacuum
  5. extractionthe aqueous phase was extracted with ether
  6. washThe combined ether extracts were washed with water
  7. customdried
  8. concentrationconcentrated
  9. customto give 4.6 g (36%) of crude
  10. customThe residue was chromatographed on silica gel eluting with chloroform
  11. customto give
  12. customafter recrystallization from methylcyclohexane

Sources & evidence

ORD record
ord-bbd9f81a7d2f495a8ac7c5511fb9270c
Source dataset
uspto-grants-1982_09
Patent number
US04348404

Reaction notes

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