phenyl 3-fluoro-6-hydroxy-2-methylbenzoate

Conditions: temp:26.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 30 L 4-neck flask equipped with mechanical stirrer, thermometer and addition funnel was charged with a solution of compound 63 (1100 g, 4.47 mol) in CH2Cl2 (8.0 L) followed by water (8.1 L) and tetrabutyl ammonium bromide (144 g, 0.45 mol). Aqueous HNO3 (591 mL, 68 w %, 8.94 mol) was added to the stirred two-phase reaction mixture at 24˜27° C. over 3 min and the mixture was stirred at 24-28° C. for 20 h. The two layers were separated and the aqueous layer was extracted with CH2Cl2 (4×1.0 L). The organic layers were then combined and successively washed with water (3×1.0 L) and brine (2×2 L). The organic layer was dried over Na2SO4 and filtered and concentrated under reduce pressure to give 1423 g (>100%) of compound 64 as dark brown solid. A 30 L 4-neck flask equipped with mechanical stirrer thermometer and addition funnel The two layers were separated the aqueous layer was extracted with CH2Cl2 (4×1.0 L) successively washed with water (3×1.0 L) and brine (2×2 L) The organic layer was dried over Na2SO4 filtered concentrated

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 30 L 4-neck flask equipped with mechanical stirrer, thermometer and gas inlet was charged with a solution of compound 62 (1140 g, 4.38 mol) in CH2Cl2 (15 L). The brown solution was cooled to −78° C. with dry ice acetone bath under small N2 flow. A solution of BBr3 in CH2Cl2 (4.5 L, 5.26 mol) was added to the reaction at −70˜−78° C. with stirring over 74 min. The reaction mixture was the allowed to warm to 20˜25° C. over 3 h and stirred at room temperature for 16 h. Saturated aqueous NaHCO3 was added to the reaction mixture slowly to pH 2˜3. After stirring for 5 min, the layers were separated and the aqueous layer was extracted with CH2Cl2 (2×1 L). The organic layers were combined and washed with brine (2×2 L). The organic layer was dried over Na2SO4 and filtered and the filtrate was concentrated under reduced pressure to give 1100 g (>100%) of crude compound 63 as brown oil: 1H NMR (400 MHz, CDCl3) δ 10.66 (s, 1H), 7.50-7.44 (m, 2H), 7.36-7.31 (m, 1H), 7.26-7.18 (m, 3H), 6.86 (dd, J=9.3, 4.9 Hz, 1H), 2.60 (d, J=2.4 Hz, 3H); MS (ESI) m/z 245.11 (M−H). A 30 L 4-neck flask equipped with mechanical stirrer to warm to 20˜25° C. over 3 h stirred at room temperature for 16 h After stirring for 5 min the layers were separated the aqueous layer was extracted with CH2Cl2 (2×1 L) washed with brine (2×2 L) The organic layer was dried over Na2SO4 filtered the filtrate was concentrated under reduced pressure