Ethyl bromoacetate → 8-Trifluoromethyl-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-3-carboxylic acid ethyl ester

HRID 418174Notes

Reaction equation

HRID 418174 reaction equation
CN(C)[CH:3]=[N:4][C:5]1[C:10]([C:11]([F:14])([F:13])[F:12])=[CH:9][C:8]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=2)=[CH:7][N:6]=1.Br[CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29].CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>CN(C=O)C>[CH2:31]([O:30][C:28]([C:27]1[N:6]2[CH:7]=[C:8]([C:15]3[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:22])[F:23])=[CH:17][CH:16]=3)[CH:9]=[C:10]([C:11]([F:12])([F:13])[F:14])[C:5]2=[N:4][CH:3]=1)=[O:29])[CH3:32]

Participants

6

Reactant 4

HCID 7748Ethyl bromoacetateHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 86611624N,N-Dimethyl-N'-[3-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyridin-2-yl]-formamidine

Product 1

HCID 866116258-Trifluoromethyl-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-3-carboxylic acid ethyl esterYield 72%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of the above N,N-dimethyl-N′-[3-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyridin-2-yl]-formamidine (3.61 g, 10.0 mmol) and ethyl bromoacetate (3.32 mL, 30.0 mmol) in DMF (10 mL) was stirred at 120° C. for 4 h. Cooled down to 100° C., added DIPEA (0.5 mL, 3.0 mmol) and stirred at 23° C. for 2 h. Poured into sat. NaHCO3-sol., extracted with EtOAc, washed the organic layers with brine, dried over Na2SO4. Removal of the solvent in vacuum left a brown oil (5.01 g) which was purified by silica gel column chromatography with heptane/EtOAc 9:1 to 4:1 to give the title compound as a light yellow solid (2.89 g, 72%). MS (ISP) 403 [(M+H)+]; mp 132° C.

Workup

  1. temperatureCooled down to 100° C.
  2. stirringstirred at 23° C. for 2 h
  3. extraction, extracted with EtOAc
  4. washwashed the organic layers with brine
  5. dry with materialdried over Na2SO4
  6. customRemoval of the solvent in vacuum
  7. waitleft a brown oil (5.01 g) which
  8. customwas purified by silica gel column chromatography with heptane/EtOAc 9:1 to 4:1

Sources & evidence

ORD record
ord-319961328a514d3b88b26f3823d91dd6
Source dataset
uspto-grants-2012_01
Patent number
US08093263B2

Reaction notes

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