4-BROMO-3-METHOXYPHENYL-P-TOLUENESULFONATE

Cupric bromide (4.88g, 21.8mmol) in acetonitril (20ml) was treated with tert- Butylnitrite (2.13ml, 17.9mmol) at rt and warmed to 65°C under nitrogen. A solution of 2 (2.24g, 16.3mmol) in acetonitril (20ml) was added slowly and stirred for additional 15 min. The solvent was removed under vacuum and taken into cyclo-hexane, washed with aqueous NH3x3, water and dried over Na2S04. The solvent was removed under vacuum and purified by flash chromatography (chloroform) to afford 3 (1.92g, 59percent yield). To a solution of cupric bromide (6.35 g; 28.4 mmol) in acetonitrille (25 ml_) was added tert- butyl nitrite (2.85 mlIntermediate 43Preparation of 1-bromo-2-methoxy-4-methylbenzeneTo a solution of copper(II)bromide (6.35 g; 28.4 mmol) in acetonitrile (25 mL) was added tert-butyl nitrite (2.85 ml; 24.06 mmol) and the mixture was heated at 65° C. under nitrogen atmosphere. A solution of 2-methoxy-4-methylaniline (3 g, 21.87 mmol) in 25 ml acetonitrile was added carefully and the mixture was stirred for 20 min at 65° C. The solvent was removed under reduced pressure, the residue was dissolved in ethyl acetate and washed with a 5percent solution of ammonia, water, a solution of EDTA, water and brine. The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. Purification by flash chromatography on silica gel using a gradient of ethyl acetate (2-50percent) in heptane furnished 2.32 g (53percent) of the title compound. To a solution of l-bromo-2-fluoro-4-methylbenzene (1.00 g, 5.29 mmol, 1 eq) in DMSO (10 mL) was added sodium methanolate (2.86 g, 52.90 mmol, 10 eq). The mixture was stirred at 130 °C for 12 h then cooled to 25 °C. Water (50 mL) was added and the aqueous phase was extracted with ethyl acetate (50 mL*3). The combined organic phases were washed with brine (50 mL*2), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Example 116B (700 mg, yield =65.8percent) was obtained as colorless oil. (0413) [0199] MR: (CDCb, 400MHz): ppm 7.40 (d, J=8.0 Hz, 1H), 6.73 (s, 1H), 6.67 (d, J=8.0 Hz, 1H), 3.89 (s, 3H), 2.33 (s, 3H).

Molecular Weight:201.06
XLogP3:3.1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:199.98368
Monoisotopic Mass:199.98368
Topological Polar Surface Area:9.2
Heavy Atom Count:10
Complexity:105
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes