Diisopropylethylamine → tert-butyl[4-(2-fluorophenyl)-2-methyl-1H-imidazol-1-yl]carbamate

HRID 931333Notes

Reaction equation

HRID 931333 reaction equation
[C:1]([NH:4][NH:5][C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])(=[NH:3])[CH3:2].Br[CH2:14][C:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[F:23])=O.C(N(CC)C(C)C)(C)C>C(#N)C.CC1CCCO1>[F:23][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[C:15]1[N:3]=[C:1]([CH3:2])[N:4]([NH:5][C:6](=[O:7])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10])[CH:14]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 27374492-Bromo-2'-fluoroacetophenoneHCID 178465665HCID 178465665, compound

Product 1

HCID 117682912tert-butyl[4-(2-fluorophenyl)-2-methyl-1H-imidazol-1-yl]carbamate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 73012-MethyltetrahydrofuranSolvent

Procedure

Compound C1 (11.4 g, 65.8 mmol), 2-bromo-1-(2-fluorophenyl)ethanone (13.0 g, 59.9 mmol) and N,N-diisopropylethylamine (23.0 mL, 132 mmol) were combined in a mixture of acetonitrile (100 mL) and 2-methyltetrahydrofuran (300 mL) and heated at reflux for 18 hours. After cooling, the reaction mixture was concentrated in vacuo; the residue was mixed with ethyl acetate, then washed sequentially with saturated aqueous ammonium chloride solution and with saturated aqueous sodium bicarbonate solution. The combined aqueous layers were extracted with ethyl acetate, and the combined organic layers were dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide the product as a pale brown foam. Yield: 18.1 g, assumed quantitative. LCMS m/z 292.4 [M+H]+. 1H NMR (500 MHz, CDCl3), presumed to be a mixture of rotamers: δ 8.15 (v br s, 1H), 8.03-8.07 (m, 1H), 7.30 and 7.31 (2 s, 1H), 7.13-7.20 (m, 2H), 7.02-7.08 (m, 1H), 2.31 (s, 3H), 1.49 (br s, 9H).

Workup

  1. temperatureheated
  2. temperatureat reflux for 18 hours
  3. temperatureAfter cooling
  4. concentrationthe reaction mixture was concentrated in vacuo
  5. additionthe residue was mixed with ethyl acetate
  6. washwashed sequentially with saturated aqueous ammonium chloride solution and with saturated aqueous sodium bicarbonate solution
  7. extractionThe combined aqueous layers were extracted with ethyl acetate
  8. dry with materialthe combined organic layers were dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-18ed679f952a452d84409d38d69862dc
Source dataset
uspto-grants-2016_03
Patent number
US09296761B2

Reaction notes

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