Water → 1-(6-Fluoro-benzo[1,3]dioxol-5-yl)-cyclopropanecarbonitrile

HRID 1991613Notes

Reaction equation

HRID 1991613 reaction equation
O.[OH-].[Na+].[F:4][C:5]1[C:6]([CH2:14][C:15]#[N:16])=[CH:7][C:8]2[O:12][CH2:11][O:10][C:9]=2[CH:13]=1.Br[CH2:18][CH2:19]Cl>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[F:4][C:5]1[C:6]([C:14]2([C:15]#[N:16])[CH2:19][CH2:18]2)=[CH:7][C:8]2[O:12][CH2:11][O:10][C:9]=2[CH:13]=1

Participants

7

Reactant 4

HCID 962WaterHCID 78491-Bromo-2-ChloroethaneHCID 14798Sodium HydroxideHCID 67044109(6-Fluoro-benzo[1,3]dioxol-5-yl)-acetonitrile

Product 1

HCID 670440561-(6-Fluoro-benzo[1,3]dioxol-5-yl)-cyclopropanecarbonitrileYield 60%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolvent2×

Procedure

A flask was charged with water (10 mL), followed by a rapid addition of NaOH (10 g, 0.25 mol) in three portions over a 5 min period. The mixture was allowed to cool to room temperature. Subsequently, the flask was charged with toluene (6 mL), tetrabutyl-ammonium bromide (50 mg, 0.12 mmol), (6-fluoro-benzo[1,3]dioxol-5-yl)-acetonitrile (600 mg, 3.4 mmol) and 1-bromo-2-chloroethane (1.7 g, 12 mmol). The mixture stirred vigorously at 50° C. overnight. The cooled flask was charged with additional toluene (20 mL). The organic layer was separated and washed with water (30 mL) and brine (30 mL). The organic layer was removed in vacuo to give the crude product, which was purified by column chromatography on silica gel (5-10% ethyl acetate/petroleum ether) to give 1-(6-fluoro-benzo[1,3]dioxol-5-yl)-cyclopropanecarbonitrile (400 mg, 60%). 1H NMR (300 MHz, CDCl3) δ 6.73 (d, J=3.0 Hz, 1H), 6.61 (d, J=9.3 Hz, 1H), 5.98 (s, 2H), 1.67-1.62 (m, 2H), 1.31-1.27 (m, 2H).

Workup

  1. customThe organic layer was separated
  2. washwashed with water (30 mL) and brine (30 mL)
  3. customThe organic layer was removed in vacuo
  4. customto give the crude product, which
  5. customwas purified by column chromatography on silica gel (5-10% ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-cff3f4bea28745fa9cd066b0fb745cb5
Source dataset
uspto-grants-2010_01
Patent number
US07645789B2

Reaction notes

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