Ethylene carbonate → 2-[2-(4-Benzyloxy-2-fluoro-phenyl)-4-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-imidazol-1-yl]-ethanol

HRID 1629525Notes

Reaction equation

HRID 1629525 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[NH:16][CH:17]=[C:18]([C:20]3[N:24]([CH:25]([CH3:27])[CH3:26])[N:23]=[CH:22][N:21]=3)[N:19]=2)=[C:11]([F:28])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:29]1[CH2:33][CH2:32]OC1=O>C1(C)C=CC=CC=1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:16]([CH2:32][CH2:33][OH:29])[CH:17]=[C:18]([C:20]3[N:24]([CH:25]([CH3:26])[CH3:27])[N:23]=[CH:22][N:21]=3)[N:19]=2)=[C:11]([F:28])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 7303Ethylene carbonateHCID 178456684HCID 178456684, compound

Product 1

HCID 582042922-[2-(4-Benzyloxy-2-fluoro-phenyl)-4-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-imidazol-1-yl]-ethanolYield 70.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

A suspension of 5-[2-(4-benzyloxy-2-fluoro-phenyl)-1H-imidazol-4-yl]-1-isopropyl-1H-[1,2,4]triazole (84 g, 0.22 mol) and [1,3]dioxolan-2-one (48 g, 0.55 mol) in toluene (100 mL) was heated at 130° C. for 7.5 h allowing some solvent to evaporate until reaction was initiated. The cooled reaction mixture was concentrated in vacuo and the residue treated with acetonitrile (50 mL), stirred, sonicated and cooled in an ice bath. The resultant solid was collected by filtration, washed with cold acetonitrile then diethyl ether and dried in vacuo at 60° C. to give 2-[2-(4-Benzyloxy-2-fluoro-phenyl)-4-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-imidazol-1-yl]-ethanol (65.2 g, 70%). 1H NMR (400 MHz, CDCl3): 8.04 (1 H, s), 7.80 (1 H, d, J=0.71 Hz), 7.43-7.41 (6 H, m), 6.89 (1 H, dd, J=8.59, 2.50 Hz), 6.79 (1 H, dd, J=11.73, 2.47 Hz), 5.93-5.92 (1 H, m), 5.11 (2 H, s), 4.02 (2 H, t, J=4.93 Hz), 3.89 (2 H, t, J=4.96 Hz), 1.49 (6 H, d, J=6.61 Hz). LCMS: RT=3.30 min, [M+H]+=422.

Workup

  1. customto evaporate until reaction
  2. customThe cooled reaction mixture
  3. concentrationwas concentrated in vacuo
  4. additionthe residue treated with acetonitrile (50 mL)
  5. customsonicated
  6. temperaturecooled in an ice bath
  7. filtrationThe resultant solid was collected by filtration
  8. washwashed with cold acetonitrile
  9. dry with materialdiethyl ether and dried in vacuo at 60° C.

Sources & evidence

ORD record
ord-d6d6c424713c4b3c8cf8999c06ccfb14
Source dataset
uspto-grants-2014_07
Patent number
US08785626B2

Reaction notes

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