Dimethylformamide → 8-Chloro-2-(4-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxaldehyde

HRID 456690

Reaction equation

HRID 456690 reaction equation
CN(C)[CH:3]=[O:4].P(Cl)(Cl)(Cl)=O.[Cl:11][C:12]1[C:13]2[N:14]([CH:18]=[C:19]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)[N:20]=2)[CH:15]=[CH:16][CH:17]=1.[OH-].[NH4+]>O>[Cl:11][C:12]1[C:13]2[N:14]([C:18]([CH:3]=[O:4])=[C:19]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)[N:20]=2)[CH:15]=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 14923Ammonium HydroxideHCID 24813Phosphorus oxychlorideHCID 179762858-Chloro-2-(4-fluorophenyl)imidazo[1,2-a]pyridine

Product 1

HCID 866010138-Chloro-2-(4-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxaldehydeYield 85%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

N,N-Dimethylformamide (10 mL) was cooled to 0° C. and treated with phosphorous oxychloride (1.0 mL, 11 mmol). After the addition was complete, the mixture was warmed to room temperature and stirred for 10 minutes. To this was added 8-chloro-2-(4-fluorophenyl)imidazo[1,2-α]pyridine (1.15 g, 4.7 mmol) and the resulting solution was stirred overnight. Water was added to the reaction. The mixture was neutralized to pH 7 with ammonium hydroxide. The aqueous phase was extracted with dichloromethane (3×50 mL). The combined organics were washed with brine, dried over magnesium sulfate, filtered and concentrated. The residue was recrystallized from acetonitrile to give 8-chloro-2-(4-fluorophenyl)imidazo[1,2-α]pyridine-3-carbaldehyde (1.1 g, 85%) as a white solid. 1H NMR (CDCl3): δ 10.05 (s, 1H), 9.60 (d, 1H), 7.86 (q, 2H), 7.65 (d, 1H), 7.23 (t, 2H), 7.08 (t, 1H); 19F NMR (CDCl3) δ −110.8; MS m/z 275 (M+1).

Workup

  1. additionAfter the addition
  2. stirringthe resulting solution was stirred overnight
  3. extractionThe aqueous phase was extracted with dichloromethane (3×50 mL)
  4. washThe combined organics were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was recrystallized from acetonitrile

Sources & evidence

ORD record
ord-b45d1ea353f94ac8a8d0bd0e9dc9edd5
Source dataset
uspto-grants-2007_03
Patent number
US07186714B2

Linked notes

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