Hydrochloric Acid → 3-(2,2-Difluorocyclopropyl)-3-oxopropanenitrile

HRID 1943908Notes

Reaction equation

HRID 1943908 reaction equation
[C:1](#[N:3])[CH3:2].C([Li])CCC.[F:9][C:10]1([F:20])[CH2:12][CH:11]1[C:13](OCCCC)=[O:14].Cl>O1CCCC1.O>[F:9][C:10]1([F:20])[CH2:12][CH:11]1[C:13](=[O:14])[CH2:2][C:1]#[N:3]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 2761400Butyl 2,2-difluorocyclopropanecarboxylateHCID 178418339Butyllithium

Product 1

HCID 670888553-(2,2-Difluorocyclopropyl)-3-oxopropanenitrileYield 82%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of acetonitrile (0.97 mL, 18.5 mmol) in tetrahydrofuran (50 mL) was cooled to −78° C. and treated with n-butyllithium in hexanes (11.7 mL, 19.0 mmol) over 5 minutes. The reaction mixture was stirred for 30 minutes, and then n-butyl 2,2-difluorocyclopropane carboxylate (3.0 g, 16.8 mmol) was added. The reaction mixture was allowed to warm to room temperature over 2 hours. The reaction mixture was poured into water (25 mL) and acidified by addition of 10% aqueous hydrochloric acid. The organic layers were extracted into diethyl ether (3×30 mL), dried (MgSO4) and concentrated to afford crude 3-(2,2-difluorocyclopropyl)-3-oxo-propionitrile (2 g).

Workup

  1. extractionThe organic layers were extracted into diethyl ether (3×30 mL)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-c64b4434900e4e1e9783088330f1ce29
Source dataset
uspto-grants-2013_03
Patent number
US08394795B2

Reaction notes

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