2'-CHLORO-6'-FLUOROACETOPHENONE

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

Procedure: 2-chloro-6-fluoroacetophenone of (A) (45.0 g, 0.26 mol) is dissolved in isopropyl alcohol (98 ml) and NaBH4 (4.9 g, 0.13 mol) is added. The resultant mixture is warmed to 55° C. for about 16 hours. A solution of NaOH 10.4 g, 0.26 mol) in water (41. ml) is then added. After 1 hour at 55° C., this reaction mixture is cooled and acidified with diluted HCl. Extraction with chloroform provided pure title product (45.1 g, 99.1%). this reaction mixture is cooled Extraction with chloroform provided pure title product (45.1 g, 99.1%)

Conditions: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-chloro-6-fluorobenzonitrile (42.3 g, 0.27 mol) is dissolved in anhydrous diethyl ether (170 ml) and methyl magnesium bromide (291 ml of a 2.8 M solution, 0.82 mol) is added. The whole is warmed to reflux (35° C.) overnight (16 hrs.). Then the reaction mixture is quenched in ice-water (380 ml) followed by the addition of concentrated H2SO4 (95 ml). The resultant mixture is heated to 100° C. for 3 hours and stirred overnight at room temperature. Pure product is then extracted from the mixture using chloroform (45.0 g, 95.9%). The whole is warmed Then the reaction mixture is quenched in ice-water (380 ml) followed by the addition of concentrated H2SO4 (95 ml) The resultant mixture is heated to 100° C. for 3 hours Pure product is then extracted from the mixture

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

Procedure: The same method as in Example 3 was conducted using 6-methyl-4,5,6,7-tetrahydrofuro[2,3-c]pyridin-4-ol (Reference Example 1) instead of 6-methyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-4-ol (Reference Example 6) and was conducted using 2-chloro-6-fluoroacetophenone instead of 1,3-difluorobenzene to give the objective compound. to give the objective compound