Ethyl Acetate → 4-Amino-2-fluoro-3-methylbenzonitrile

HRID 1047287Notes

Reaction equation

HRID 1047287 reaction equation
Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([CH3:9])[C:3]=1[F:10].[C:11]([Cu])#[N:12].C(OCC)(=O)C>CCCCCC>[NH2:6][C:5]1[CH:7]=[CH:8][C:2]([C:11]#[N:12])=[C:3]([F:10])[C:4]=1[CH3:9]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 157466844-Bromo-3-fluoro-2-methylanilineHCID 178418546HCID 178418546, compound

Product 1

HCID 450786764-Amino-2-fluoro-3-methylbenzonitrileYield 67.3%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 4-bromo-3-fluoro-2-methylaniline (23 g, 113 mmol) and cyanocopper (20.19 g, 225 mmol) N,N-dimethylformamide (200 mL) was heated to 140° C. for 7 h. After the mixture was cooled to room temperature filtered and poured into a reparatory funnel containing water and ethyl acetate (1:1). Layers were separated and the organic layer was concentrated under reduced pressure. Flash chromatography (0-50% ethyl acetate in hexane) gave the desired product (11.4 g, 76 mmol, 67% yield) as a brown solid. 1H NMR (400 MHz, CHLOROFORM-d) δ (ppm) 7.22 (t, 1H), 6.45 (d, J=8.59 Hz, 1H), 4.23 (br. s., 2H), 2.07 (s, 3H); MS (ESI) m/z 151.1 [M+1]+.

Workup

  1. temperatureAfter the mixture was cooled to room temperature
  2. filtrationfiltered
  3. additionpoured into a reparatory funnel
  4. additioncontaining water and ethyl acetate (1:1)
  5. customLayers were separated
  6. concentrationthe organic layer was concentrated under reduced pressure

Sources & evidence

ORD record
ord-ec123014d4a34cc0b1bc6b13213ad543
Source dataset
uspto-grants-2013_10
Patent number
US08569494B2

Reaction notes

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