1,2-Dibromoethane → Ethyl 1-(2-bromoethyl)-3-(4-fluorophenyl)-1H-pyrazole-5-carboxylate

HRID 920706Notes

Reaction equation

HRID 920706 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[NH:10][N:9]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[Br:24][CH2:25][CH2:26]Br>C(#N)C>[Br:24][CH2:25][CH2:26][N:10]1[C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:12][C:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)=[N:9]1

Participants

5

Reactant 3

HCID 78391,2-DibromoethaneHCID 11430Potassium CarbonateHCID 583549Ethyl 3-(4-fluorophenyl)-1h-pyrazole-5-carboxylate

Product 1

HCID 118061974Ethyl 1-(2-bromoethyl)-3-(4-fluorophenyl)-1H-pyrazole-5-carboxylateYield 45.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of Intermediate 1B (135 g, 576 mmol) and potassium carbonate (159 g, 1153 mmol) in acetonitrile (1400 mL) was added 1,2-dibromoethane (59.6 mL, 692 mmol) and the resulting reaction mixture was refluxed for 4 h. Acetonitrile was removed under reduced pressure and the residue was diluted with water. The aqueous layer was extracted with DCM (2×500 mL) The combined organic layer was washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by ISCO using 880 g REDISEP® column and 1% methanol in chloroform as eluent. Combined fractions were concentrated to afford Intermediate 1C (90 g, 45%). MS(ES): m/z=343 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.91-7.97 (m, 2H), 7.41 (s, 1H), 7.24-7.30 (m, 2H), 4.96 (t, J=6.34 Hz, 2H), 4.36 (q, J=7.11 Hz, 2H), 3.90 (t, J=6.34 Hz, 2H), 1.35 (t, J=7.12 Hz, 3H).

Workup

  1. customthe resulting reaction mixture
  2. temperaturewas refluxed for 4 h
  3. customAcetonitrile was removed under reduced pressure
  4. additionthe residue was diluted with water
  5. extractionThe aqueous layer was extracted with DCM (2×500 mL) The combined organic layer
  6. washwas washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by ISCO
  11. concentrationCombined fractions were concentrated

Sources & evidence

ORD record
ord-140c4e596866492399702be3fbf1d118
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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