4-Chlorobenzaldehyde → ethyl 4-((4-chlorophenyl)(hydroxy)methyl)-1-cyclopropyl-5-(trifluoromethyl)-1H-Pyrazole-3-carboxylate

HRID 873864Notes

Reaction equation

HRID 873864 reaction equation
[Li+].CC([N-]C(C)C)C.[CH:9]1([N:12]2[C:16]([C:17]([F:20])([F:19])[F:18])=[CH:15][C:14]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[N:13]2)[CH2:11][CH2:10]1.[Cl:26][C:27]1[CH:34]=[CH:33][C:30]([CH:31]=[O:32])=[CH:29][CH:28]=1>C1COCC1>[Cl:26][C:27]1[CH:34]=[CH:33][C:30]([CH:31]([OH:32])[C:15]2[C:14]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[N:13][N:12]([CH:9]3[CH2:10][CH2:11]3)[C:16]=2[C:17]([F:18])([F:19])[F:20])=[CH:29][CH:28]=1

Participants

5

Reactant 3

HCID 77264-ChlorobenzaldehydeHCID 2724682Lithium diisopropylamideHCID 117703039ethyl 1-cyclopropyl-5-(trifluoromethyl)-1H-pyrazole-3-carboxylate

Product 1

HCID 117702816ethyl 4-((4-chlorophenyl)(hydroxy)methyl)-1-cyclopropyl-5-(trifluoromethyl)-1H-Pyrazole-3-carboxylateYield 71.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

LDA (3.70 mL, 6.66 mmol) was added dropwise to a stirred solution of ethyl 1-cyclopropyl-5-(trifluoromethyl)-1H-pyrazole-3-carboxylate (Step 40.1) (1.18 g, 4.75 mmol) in THF (30 mL). After 15 minutes at −78° C., a solution of 4-chlorobenzaldehyde (668 mg, 4.75 mmol) in THF (5 mL) was slowly added. The reaction was stirred at −78° C. for 15 min, quenched with 1 mL of saturated NH4Cl solution, partitioned between EtOAc and water and both phases separated. The aq. phase was extracted with EtOAc and the combined organic phases were washed with brine, dried over Na2SO4 and concentrated. The crude was purified by silica gel column chromatography (hexane/20% EtOAc) to afford the title product (1.5 g, 3.40 mmol, 71% yield) as a yellow solid. tR: 1.27 min (LC-MS 2); ESI-MS: 389 [M+H]+ (LC-MS 2); Rf=0.22 (hexane/EtOAc 8:2).

Workup

  1. customquenched with 1 mL of saturated NH4Cl solution
  2. custompartitioned between EtOAc and water
  3. customboth phases separated
  4. extractionThe aq. phase was extracted with EtOAc
  5. washthe combined organic phases were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe crude was purified by silica gel column chromatography (hexane/20% EtOAc)

Sources & evidence

ORD record
ord-f8024420f84047ce99467cdb02dd5554
Source dataset
uspto-grants-2015_03
Patent number
US08975417B2

Reaction notes

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