Hydrochloric Acid → tert-butyl 1-(4-chloro-1H-pyrazol-1-yl)cyclopropanecarboxylate

HRID 931175Notes

Reaction equation

HRID 931175 reaction equation
C[Si](C)(C)[O-].[K+].[Cl:7][C:8]1[CH:9]=[N:10][NH:11][CH:12]=1.Br[CH:14]([CH2:22][CH2:23]Br)[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16].Cl>CC1CCCO1.BrC(CCBr)C(OC(C)(C)C)=O.C[Si](C)(C)[O-].[K+]>[Cl:7][C:8]1[CH:9]=[N:10][N:11]([C:14]2([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:23][CH2:22]2)[CH:12]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 275241H-Pyrazole, 4-chloro-HCID 5107723tert-Butyl 2,4-dibromobutyrateHCID 23668039Potassium trimethylsilanolate2×

Product 1

HCID 117966667tert-butyl 1-(4-chloro-1H-pyrazol-1-yl)cyclopropanecarboxylateYield 126.7%

Reagents, catalysts & solvents 3

HCID 5107723tert-Butyl 2,4-dibromobutyrateCatalyst3×HCID 23668039Potassium trimethylsilanolateCatalystHCID 73012-MethyltetrahydrofuranSolvent2×

Procedure

Into a flask was added potassium trimethylsilanolate (20.85 g, 146.31 mmol), 4-chloro-1H-pyrazole (15 g, 146.31 mmol) and 2-methyltetrahydrofuran (400 mL). The mixture was stirred for 5 min followed by the addition of tert-butyl 2,4-dibromobutyrate (27.84 mL, 146.31 mmol) over a period of 20 to 30 seconds. The reaction mixture was stirred for 60 min. Potassium trimethylsilanolate (20.85 g, 146.31 mmol) in 2-methyltetrahydrofuran (80 mL) was added over a period of 5 min. The reaction mixture was stirred for 1 h before adding tert-butyl 2,4-dibromobutyrate (1 mL, 5.3 mmol). After 30 min, an additional portion of tert-butyl 2,4-dibromobutyrate (2 mL, 10.5 mmol) was added. The mixture was stirred for 40 min before adding tert-butyl 2,4-dibromobutyrate (1 mL, 5.3 mmol) and potassium trimethylsilanolate (2 g, 14 mmol). The reaction mixture was stirred for 18 h. Hydrochloric acid (146.31 mL, 146.31 mmol) was added and the mixture was stirred for 5 min. The layers were separated, and the organics were washed with water (200 mL) and concentrated under reduced pressure. Toluene (100 mL) was added and the mixture was concentrated to dryness to afford tert-butyl 1-(4-chloro-1H-pyrazol-1-yl)cyclopropanecarboxylate (45 g). 1H NMR (400 MHz, CDCl3): δ 1.40 (s, 9H), 1.57 (q, 2H), 1.75 (q, 2H), 7.44 (s, 1H), 7.51 (s, 1H); MS (EI+) (M+) 242; GCMS retention time: 2.37 minutes (Method O).

Workup

  1. stirringThe reaction mixture was stirred for 60 min
  2. stirringThe reaction mixture was stirred for 1 h
  3. waitAfter 30 min
  4. stirringThe mixture was stirred for 40 min
  5. stirringThe reaction mixture was stirred for 18 h
  6. stirringthe mixture was stirred for 5 min
  7. customThe layers were separated
  8. washthe organics were washed with water (200 mL)
  9. concentrationconcentrated under reduced pressure
  10. additionToluene (100 mL) was added
  11. concentrationthe mixture was concentrated to dryness

Sources & evidence

ORD record
ord-2bc421342e3141dd91001d2a12dbf055
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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