Potassium Phosphate, Tribasic → 2-Chloro-4-cyclopropyl-5-methyl-6-fluoroaniline

2-Chloro-4-bromo-5-methyl-6-fluoroaniline (6.5 g, 27 mmol), cyclopropylboronic acid (2.8 g, 33 mmol), tetrakis (triphenylphosphine)palladium (0) (1.4 g, 1.3 mmol), potassium phosphate (20.2 g, 95 mmol) and tricyclohexylphosphine (0.77 g, 2.7 mmol) are combined and stirred in 200 mL of a 4:1 DME/water solution. The mixture is degassed by repeated alternating application of vacuum and positive nitrogen pressure (10×). The mixture is heated to reflux temperature for 2 days and then cooled to room temperature. Most of the DME is removed by rotary evaporator and the residual mixture is partitioned between Et2O (250 mL) and water (250 mL). The organic phase is washed with brine (3×250 mL), dried (MgSO4) and concentrated by rotary evaporator. The crude product is purified using flash chromatography (8% CH2Cl2/hexanes) to give 2-chloro-4-cyclopropyl-5-methyl-6-fluoroaniline as a tan oil.

1. customThe mixture is degassed by repeated alternating application of vacuum and positive nitrogen pressure (10×)
2. temperatureThe mixture is heated
3. temperatureto reflux temperature for 2 days
4. customMost of the DME is removed by rotary evaporator
5. customthe residual mixture is partitioned between Et2O (250 mL) and water (250 mL)
6. washThe organic phase is washed with brine (3×250 mL)
7. dry with materialdried (MgSO4)
8. concentrationconcentrated by rotary evaporator
9. customThe crude product is purified

ORD record

ord-2baa8c18e5704287afaadc91bd50569f

Source dataset

uspto-grants-2007_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07202364B2