(+-)-2-Butanol → 1-(5-(4-chlorophenyl)-1-methyl-1H-imidazol-4-yl)-2-(3,5-difluorophenyl)ethanamine

HRID 1506659Notes

Reaction equation

HRID 1506659 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH3:13])[CH:11]=[N:10][C:9]=2[C:14]#[N:15])=[CH:4][CH:3]=1.[F:16][C:17]1[CH:18]=[C:19]([CH:23]=[C:24]([F:26])[CH:25]=1)[CH2:20][Mg]Br.CC(O)CC.[BH4-].[Na+]>C1(C)C=CC=CC=1.C(OCC)C.CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:12]([CH3:13])[CH:11]=[N:10][C:9]=2[CH:14]([NH2:15])[CH2:20][C:19]2[CH:18]=[C:17]([F:16])[CH:25]=[C:24]([F:26])[CH:23]=2)=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 6568(+-)-2-ButanolHCID 4311764Sodium borohydrideHCID 841273375-(4-chlorophenyl)-1-methyl-1H-imidazole-4-carbonitrileHCID 178505920HCID 178505920, compound

Product 1

HCID 902813971-(5-(4-chlorophenyl)-1-methyl-1H-imidazol-4-yl)-2-(3,5-difluorophenyl)ethanamine

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 5-(4-chlorophenyl)-1-methyl-1H-imidazole-4-carbonitrile (520 mg, 2.4 mmol) in toluene (13 mL) at 0° C. was added (3,5-difluorobenzyl)magnesium bromide (12.5 mL of a 0.25 M solution in diethylether). The reaction was stirred 20 min at 0° C. then let warm to ambient temperature. After stirring for 40 min, the reaction was cooled to 0° C. 2-Butanol (8 mL) and MeOH (4 mL) were added followed by addition of NaBH4 (135 mg, 3.6 mmol) and stirred for 20 min. The reaction was quenched by addition of saturated aqueous NH4Cl and extracted with EtOAc. The organics were separated, washed with saturated aqueous NaHCO3, and dried with saturated aqueous NaCl. Solvents were removed in vacuo and the residue purified by column chromatography on silica to provide the desired product. MS (m/z) 348.3 [M+H]+.

Workup

  1. temperaturethen let warm to ambient temperature
  2. stirringAfter stirring for 40 min
  3. temperaturethe reaction was cooled to 0° C
  4. stirringstirred for 20 min
  5. customThe reaction was quenched by addition of saturated aqueous NH4Cl
  6. extractionextracted with EtOAc
  7. customThe organics were separated
  8. washwashed with saturated aqueous NaHCO3
  9. dry with materialdried with saturated aqueous NaCl
  10. customSolvents were removed in vacuo
  11. customthe residue purified by column chromatography on silica

Sources & evidence

ORD record
ord-36ed354ddbdd443b89c677ba0b657e0d
Source dataset
uspto-grants-2015_12
Patent number
US09220710B2

Reaction notes

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