Diethyl Ether → 2-Fluoro-4-(hydroxy(1-methyl-1h-imidazol-5-yl)methyl)benzonitrile

HRID 1348902Notes

Reaction equation

HRID 1348902 reaction equation
I[C:2]1[N:6]([CH3:7])[CH:5]=[N:4][CH:3]=1.C1([Mg]Br)C=CC=CC=1.C(OCC)C.[F:21][C:22]1[CH:29]=[C:28]([CH:30]=[O:31])[CH:27]=[CH:26][C:23]=1[C:24]#[N:25]>ClCCl>[F:21][C:22]1[CH:29]=[C:28]([CH:30]([OH:31])[C:2]2[N:6]([CH3:7])[CH:5]=[N:4][CH:3]=2)[CH:27]=[CH:26][C:23]=1[C:24]#[N:25]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 12776685-Iodo-1-methyl-1H-imidazoleHCID 112173392-Fluoro-4-formylbenzonitrileHCID 178418255HCID 178418255, compound

Product 1

HCID 185332012-Fluoro-4-(hydroxy(1-methyl-1h-imidazol-5-yl)methyl)benzonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 5-iodo-1-methyl-1H-imidazole (250 mg, 1.2 mmol) in dichloromethane (2 mL) at 0° C. was treated with 3M phenylmagnesium bromide in diethyl ether (0.4 mL, 1.2 mmol), stirred for 30 minutes, warmed to room temperature, stirred for 30 minutes, cooled to 0° C. and treated with a solution of Example 52C (150 mg, 1.0 mmol) in dichloromethane (1 mL). The mixture was warmed to room temperature, stirred for 2 days, and quenched with ethyl acetate and saturated ammonium chloride. The aqueous phase was extracted with ethyl acetate (2×100 mL), and the combined organic layers were dried (MgSO4), filtered, and concentrated. The concentrate was dissolved in 1:1 ethyl acetate/diethyl ether, filtered, rinsed with 1:1 ethyl acetate/diethyl ether and dried to provide the desired product. 1H NMR (400 MHz, CD3OD) δ 7.91 (dd, 1H), 7.56 (s, 1H), 7.51 (d, 1H), 7.42-7.38 (m, 1H), 6.42 (s, 1H), 6.28-6.24 (m, 1H), 5.93-5.91 (m, 1H), 3.52 (s, 3H).

Workup

  1. stirringstirred for 30 minutes
  2. temperaturecooled to 0° C.
  3. temperatureThe mixture was warmed to room temperature
  4. stirringstirred for 2 days
  5. customquenched with ethyl acetate and saturated ammonium chloride
  6. extractionThe aqueous phase was extracted with ethyl acetate (2×100 mL)
  7. dry with materialthe combined organic layers were dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. dissolutionThe concentrate was dissolved in 1:1 ethyl acetate/diethyl ether
  11. filtrationfiltered
  12. washrinsed with 1:1 ethyl acetate/diethyl ether
  13. customdried

Sources & evidence

ORD record
ord-657ba9aefba040fa897303884661eb33
Source dataset
uspto-grants-2007_05
Patent number
US07211595B2

Reaction notes

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