Imidazole → HCID 86591885, compound

HRID 583918Notes

Reaction equation

HRID 583918 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]([OH:11])[CH3:10].[C:12]([CH2:16][Si:17](Cl)([CH3:19])[CH3:18])([CH3:15])([CH3:14])[CH3:13].N1C=CN=C1>CN(C=O)C>[C:12]([CH2:16][Si:17]([O:11][CH:9]([C:3]1[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=1[F:1])[CH3:10])([CH3:19])[CH3:18])([CH3:15])([CH3:14])[CH3:13]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 146531531-(2,4-Difluorophenyl)ethanolHCID 85655608HCID 85655608, compound

Product 1

HCID 86591885HCID 86591885, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2′,4′-difluoroacetophenone (5 g, 32 mmol) was reacted with sodium borohydride (1.21 g) in THF (20 mL) and methanol (10 mL) for 1 hr. The resultant mixture was evaporated to dryness and partitioned between methylene chloride and water. The organic layer was separated, dried, and evaporated to give 1-(2′,4′-difluorophenyl)-ethanol as a colorless oil (4.86 g, 96%). 1H NMR (300 MHz, CDCl3) δ 7.48 (m, 1H), 6.85 (m, 1H), 6.75 (m, 1H), 5.15 (q, 1H), 2.0 (s, 1H), 1.5 (d, 3H). 1-(2′,4′-difluorophenyl)-ethanol (5.384 g, 34 mmol), t-butyltrimethylsilyl chloride (6.148 g, 40.8 mmol) and imidazole (5.567 g, 81.8 mmol) in DMF (60 mL) were combined and stirred at rt overnight. The resultant mixture was evaporated to dryness in vacuo, and then the residue was partitioned between methylene chloride and water. The organic layer was separated, dried and evaporated to give 1-(2′,4′-difluorophenyl)-ethyl t-butyltrimethylsilyl ether as a white solid (6.88 g, 74%). 1H NMR (300 MHz, CDCl3) δ 7.45 (q, 1H), 6.75 (m, 1H), 6.62 (m, 1H), 5.05 (q, 1H), 1.32 (d, 3H), 0.88 (s, 9H), 0.05 and 0.01 (each s, each 3H). A 1.6 M solution of n-butyl lithium in hexane (3.75 mL, 6 mmol) was added dropwise to a solution of 1-(2′,4′-difluorophenyl)-ethyl t-butyltrimethylsilyl ether (1.362 g, 5 mmol) in THF (60 mL) at −50° C. and was stirred at the same temperature for 3 h. The reaction mixture was poured to dry ice; and then was evaporated to dryness. The residue was partitioned between methylene chloride and water, acidified with acetic acid. The organic layer was separated, dried, and evaporated to give 2,6-difluoro-3-(1-t-butyltrimethylsilyloxyethyl)-benzoic acid Compound 5A as white solid (1.57 g, 99%). 1H NMR (300 MHz, CDCl3) δ 7.70 (q, 1H), 7.00 (t, 1H), 6.00 (br, 1H), 5.15 (q, 1H), 1.40 (d, 3H), 0.90 (s, 9H), 0.12 and 0.05 (each s, each 3H).

Workup

  1. customThe resultant mixture was evaporated to dryness in vacuo
  2. customthe residue was partitioned between methylene chloride and water
  3. customThe organic layer was separated
  4. customdried
  5. customevaporated

Sources & evidence

ORD record
ord-75feaff2a1974875b8fcd26bad07e93a
Source dataset
uspto-grants-2005_08
Patent number
US06924302B2

Reaction notes

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