Sodium hydride → benzyl 1-(4-fluoro-1H-pyrazol-1-yl)cyclopropanecarboxylate

HRID 931064Notes

Reaction equation

HRID 931064 reaction equation
[F:1][C:2]1[CH:3]=[N:4][NH:5][CH:6]=1.[H-].[Na+].Br[CH:10]([CH2:21][CH2:22]Br)[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12]>O1CCCC1.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[N:4][N:5]([C:10]2([C:11]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[O:12])[CH2:22][CH2:21]2)[CH:6]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 1419924-fluoro-1H-pyrazoleHCID 4338264Benzyl 2,4-dibromobutanoate

Product 1

HCID 89853924benzyl 1-(4-fluoro-1H-pyrazol-1-yl)cyclopropanecarboxylateYield 30.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-fluoropyrazole (125 mg, 1.45 mmol) in tetrahydrofuran (4 mL) at 0° C. was added sodium hydride (60% suspension in mineral oil, 116 mg, 2.90 mmol). The mixture was stirred at 0° C. for 40 min before benzyl 2,4-dibromobutyrate (0.30 mL, 1.50 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 18 h. The reaction mixture was diluted with ethyl acetate and washed with water and brine. The organics were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified via flash chromatography to afford benzyl 1-(4-fluoro-1H-pyrazol-1-yl)cyclopropanecarboxylate as a clear oil (115 mg, 30.4%). 1H NMR (400 MHz, CDCl3) δ 1.64-1.70 (m, 2H), 1.81-1.86 (m, 2H), 5.14 (s, 2H), 7.22-7.26 (m, 2H), 7.31-7.36 (m, 3H), 7.40 (td, 2H).

Workup

  1. additionwas added dropwise
  2. washwashed with water and brine
  3. dry with materialThe organics were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified via flash chromatography

Sources & evidence

ORD record
ord-0f7afdc147734989a7e4300796423c83
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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