Ethanol → HCID 54074511, compound

HRID 1417534Notes

Reaction equation

HRID 1417534 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:10](=[N:17]N(C)C)[C:11](=O)[C:12]([F:15])([F:14])[F:13])[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].C(O)C.C(OCC)(=O)C.BrC1C=C(C2N(C)[CH:42]=[N:41][C:40]=2C(F)(F)F)C=CC=1OC>C1(C)C=CC=CC=1.CCCCCC>[Br:1][C:2]1[CH:3]=[C:4]([C:10]2[N:17]=[CH:40][N:41]([CH3:42])[C:11]=2[C:12]([F:13])([F:14])[F:15])[CH:5]=[CH:6][C:7]=1[O:8][CH3:9]

Participants

7

Reactant 4

HCID 702EthanolHCID 8857Ethyl Acetate2×HCID 53655014HCID 53655014, compoundHCID 53882490HCID 53882490, compound

Product 1

HCID 54074511HCID 54074511, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8058HexaneSolvent2×

Procedure

Using the general procedure of S. Ohara, K. Kawasaki, Y. Kawamura, and M. Tanaka (J. Heterocyclic Chem., 1990, 27, 487-495), silica gel (EM silica gel 60, 230-400 mesh) was dried under vacuum at 180° C. for 2 h. A suspension of 1.80 g of this activated silica gel was stirred in 9 mL of dry toluene and 3-(3-bromo-4-methoxyphenyl)-3-(dimethylhydrazono)-1,1,1-trifluoropropan-2-one (250 mg 0.71 mmol) was added as a solution in 5 mL of toluene. The resulting suspension was heated to reflux for 48 h, then allowed to cool to room temperature and stirred overnight. After the addition of 95% ethanol (20 mL) the mixture was stirred for 10 min and filtered. The silica gel was stirred with 20 mL of 95% ethanol and filtered, and the process was repeated again. Evaporation of the combined filtrates gave a pale amber oil. Flash column chromatography on 15 g of silica gel eluting with 10% ethyl acetate in hexane followed by 15% ethyl acetate in hexane gave 167 mg of 4-(3-bromo-4-methoxyphenyl)-5-trifluoromethyl-1-methylimidazole and 5-(3-bromo-4-methoxyphenyl)-4-trifluoromethyl-1-methylimidazole as a 6:1 mixture as determined by NMR. This material was recrystallized from a 65° C. solution in hexane (0.75 mL) and toluene (0.15 mL) cooled to -10° C. Recrystallization again from a 65° C. solution in hexane (0.75 mL) and toluene (0.15 mL) cooled to room temperature gave 112 mg of 4-(3-bromo-4-methoxyphenyl)-5-trifluoromethyl-1-methylimidazole as white crystals. Concentration of the mother liquors yielded 48 mg of 4-(3-bromo-4-methoxyphenyl)-5-trifluoromethyl-1-methylimidazole and 5-(3-bromo-4-methoxyphenyl)-4-trifluoromethyl-1-methylimidazole as a 1:1 mixture as determined by NMR. 4-(3-Bromo-4-methoxyphenyl)-5-trifluoromethyl-1-methylimidazole: 1H NMR (400 MHz, CDCl3): δ 7.78 (d, 1H, J=2 Hz), 7.75 (s, 1H), 7.47 (bd, 1H, J=8 Hz), 6.93 (d, 1H, J=8 Hz), 3.94 (s, 3H), 3.81 (s, 3H). Mass spectrum (ESI): m/e=335 (M+1).

Workup

  1. dry with materialTanaka (J. Heterocyclic Chem., 1990, 27, 487-495), silica gel (EM silica gel 60, 230-400 mesh) was dried under vacuum at 180° C. for 2 h
  2. additionA suspension of 1.80 g of this activated silica gel
  3. temperatureThe resulting suspension was heated
  4. temperatureto reflux for 48 h
  5. stirringstirred overnight
  6. stirringwas stirred for 10 min
  7. filtrationfiltered
  8. stirringThe silica gel was stirred with 20 mL of 95% ethanol
  9. filtrationfiltered
  10. customEvaporation of the combined filtrates
  11. customgave a pale amber oil

Sources & evidence

ORD record
ord-5b5618ccf8a74d63a5cfd90cf3d7e166
Source dataset
uspto-grants-1999_03
Patent number
US05877191

Reaction notes

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