Potassium Carbonate → 5-Methyl-3-(3-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-2-carboxylic acid ethyl ester

HRID 1473954Notes

Reaction equation

HRID 1473954 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH3:14])[N:9]2[C:15]=1Br)=[O:5])[CH3:2].C(=O)([O-])[O-].[K+].[K+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:42][C:43]([F:54])([F:53])[C:44]1[CH:45]=[C:46](B(O)O)[CH:47]=[CH:48][CH:49]=1>CC([O-])=O.CC([O-])=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd+2]>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH3:14])[N:9]2[C:15]=1[C:48]1[CH:47]=[CH:46][CH:45]=[C:44]([C:43]([F:54])([F:53])[F:42])[CH:49]=1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 58379339Ethyl 3-bromo-5-methylimidazo[1,2-a]pyridine-2-carboxylate

Product 1

HCID 594961435-Methyl-3-(3-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-2-carboxylic acid ethyl esterYield 50.2%

Reagents, catalysts & solvents 1

HCID 84538Palladium(2+) acetate--triphenylphosphane (1/2/2)Catalyst

Conditions

Temperature
120 °C

Procedure

3-Bromo-5-methyl-imidazo[1,2-a]pyridine-2-carboxylic acid ethyl ester (compound o, 0.6 g, 0.002 mol), potassium carbonate (0.6 g, 0.004 mol), triphenylphosphine (0.06 g, 0.0002 mol), 3-(trifluoromethyl)phenylboronic acid (0.4 g, 0.002 mol) and bis(acetato) bis(triphenylphosphine)palladium (II) (0.08 g, 0.0001 mol) were mixed in a microwave vial. The mixture was purged with argon. Isopropyl alcohol (20 mL) and water (3 mL) was added. The mixture was heated (120° C.) by microwaved for 25 minutes. The solvent removed then water (10 mL) and ethyl acetate (10 mL) was added. The layers were separated and the organic layer dried (magnesium sulfate) then removed. The crude product was chromatographed using 50% ethyl acetate/hexanes to give 350 mg of 5-methyl-3-(3-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-2-carboxylic acid ethyl ester as a white solid. Rf 0.42, 50% ethyl acetate/hexanes; MS m/z 349 (M+H).

Workup

  1. customThe mixture was purged with argon
  2. additionIsopropyl alcohol (20 mL) and water (3 mL) was added
  3. customby microwaved for 25 minutes
  4. customThe solvent removed
  5. additionwater (10 mL) and ethyl acetate (10 mL) was added
  6. customThe layers were separated
  7. dry with materialthe organic layer dried (magnesium sulfate)
  8. customthen removed
  9. customThe crude product was chromatographed

Sources & evidence

ORD record
ord-42e7cf42275145ea8c5c5472de289296
Source dataset
uspto-grants-2015_04
Patent number
US09018208B2

Reaction notes

Loading…