Ethyl Acetate → 5-Cyclopropyl-2-fluoroaniline

HRID 2200158Notes

Reaction equation

HRID 2200158 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:9])=[C:6]([CH:8]=1)[NH2:7].[CH:10]1(B(O)O)[CH2:12][CH2:11]1.C(=O)([O-])[O-].[Cs+].[Cs+].CCOC(C)=O>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:10]1([C:2]2[CH:3]=[CH:4][C:5]([F:9])=[C:6]([CH:8]=2)[NH2:7])[CH2:12][CH2:11]1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 2760897Cyclopropylboronic acidHCID 27694075-Bromo-2-fluoroaniline

Product 1

HCID 675036775-Cyclopropyl-2-fluoroanilineYield 55%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Stir the mixture of 5-bromo-2-fluoroaniline (800 mg, 4.26 mmol), cyclopropylboronic acid (434 mg, 5.05 mmol), tetrakis(triphenylphosphine)palladium(0) (242 mg, 0.21 mmol), cesium carbonate (2.7 g, 8.28 mmol) in dioxane (5 mL) and water (0.3 mL) under N2 atmosphere at 100° C. for 17 hrs. TLC (EtOAc:PE=1:3) shows the reaction is complete. Filter off the solid, concentrate the filtrate. Purify by flash chromatography (silica gel, EtOAc:PE=3:7) to afford the title compound (350 mg, 55%). MS: (M+1): 152.1.

Workup

  1. filtrationFilter off the solid
  2. concentrationconcentrate the filtrate
  3. customPurify by flash chromatography (silica gel, EtOAc:PE=3:7)

Sources & evidence

ORD record
ord-8ea75f5afb4442588e248baa1683cbaa
Source dataset
uspto-grants-2016_06
Patent number
US09359338B2

Reaction notes

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