Phenol, 2,6-difluoro-3-methyl- (9CI) synthesis

Yield:1434722-11-8 74%

Reaction Conditions:

with pyridine;pyridine N-oxide;copper diacetate in dichloromethane at 20;Molecular sieve;

Steps:

1

Synthesis of Key Intermediate 1(S)-1-(2.4-Difluoro-3-phenoxy-phenyl)-propylamineStep 1 A mixture of 2,6-difluoro-3-methylphenol (10.1 g, 70 mmol), phenyl boronic acid(8.6 g, 70 mmol), copper (II) acetate (12.7 g, 70 mmol), pyridine (29 ml, 350 mmol), pyridine N- oxide (7.3 g, 77 mmol) and powdered 4A molecular sieves (12.8 g) in DCM (400 ml) was stirred at room temperature overnight. The reaction mixture was filtered and the filtrate concentrated. The residue was partitioned between 2M HCI and petrol. The organic fractions were dried over magnesium sulfate, filtered and concentrated to afford 2,4-difluoro-3-phenoxytoluene (11.34 g, 74%) as a pale yellow liquid. ¹H NMR (400 MHz, CDCI₃): 7.40-7.18 (2H, m), 7.18-7.06 (1H, m), 7.06-6.84 (4H, m), 2.30 (3H, s).

References:

WO2013/64538,2013,A1 Location in patent:Page/Page column 100