(2-amino-5-iodo-3-methylphenyl)methanol

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

Procedure: n-Butyllithium (33 cm3 of a 1.6M solution in n-hexane) was added to a stirred solution of 2-methoxy-5-bromopyridine (9.4g) in tetrahydrofuran (THF) (70 cm3) at -70° under nitrogen. After stirring for 1 hour at -70° the mixture treated with a solution of anhydrous zinc chloride (14.2 g) in THF (70 cm3) and the mixture was warmed to room temperature. 2-Amino-5-iodo-3-methylbenzyl alcohol (3.9 g--see preparation 8) and tetrakis(triphenylphosphine) palladium (0) (0.4 g) were added and the mixture heated under reflux for 3 hours. Saturated ammonium chloride solution (50 cm3) was added to the cooled solution and the mixture was partitioned between ethyl acetate (300 cm3) and a solution of ethylenediaminetetraacetic acid disodium salt (20 g) in water (300 cm3). The aqueous phase was further extracted with ethyl acetate (300 cm3) and the combined and dried (MgSO4) organic phases were evaporated in vacuo to give a brown oil which was chromatographed on silica (Merck "MK 60.9385" [Trade Mark]) eluting with dichloromethane:methanol, 49:1. Combination and evaporation of appropriate fractions afforded the title compound as a waxy solid, m.p. 80°-82° (3.6 g), which was used directly without further purification. the mixture heated under reflux for 3 hours the mixture was partitioned between ethyl acetate (300 cm3) The aqueous phase was further extracted with ethyl acetate (300 cm3) dried (MgSO4) organic phases were evaporated in vacuo to give a brown oil which was chromatographed on silica (Merck "MK 60.9385" [Trade Mark]) eluting with dichloromethane Combination and evaporation of appropriate fractions

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

Procedure: Freshly dried manganese dioxide (3.3 g) was added to a solution of 2-amino-5-iodo-3-methylbenzyl alcohol (2.0 g) in dichloromethane (50 cm3) under nitrogen and the mixture was stirred for 3 days at room temperature. The mixture was filtered, the filtrate evaporated to dryness, and the solid residue was chromatographed on silica (Merck "MK 60.9385" [Trade Mark]) eluting with dichloromethane. Combination and evaporation of appropriate fractions afforded the title compound, m.p. 134° (1.6 g). The mixture was filtered the filtrate evaporated to dryness the solid residue was chromatographed on silica (Merck "MK 60.9385" [Trade Mark]) eluting with dichloromethane Combination and evaporation of appropriate fractions

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

Procedure: Freshly dried manganese dioxide (3.3 g) was added to a solution of 2-amino-5-iodo-3-methylbenzyl alcohol (2.0 g) in dichloromethane (50 cm3) under nitrogen and the mixture was stirred for 3 days at room temperature. The mixture was filtered, the filtrate evaporated to dryness, and the solid residue was chromatographed on silica (Merck "MK 60.9385" [Trade Mark]) eluting with dichloromethane. Combination and evaporation of appropriate fractions afforded the title compound, m.p. 134° (1.6 g). The mixture was filtered the filtrate evaporated to dryness the solid residue was chromatographed on silica (Merck "MK 60.9385" [Trade Mark]) eluting with dichloromethane Combination and evaporation of appropriate fractions

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

Procedure: A solution of borane in THF (270 cm3 of a 1M solution) was added over 0.5 hours to a stirred suspension of 2-amino-5-iodo-3-methylbenzoic acid (18.48 g) in THF (400 cm3) at 0°. After stirring at 0° for 0.5 hours, the reaction mixture was warmed to 50° for a further 3 hours. After cooling in an ice-bath, water (25 cm3) was cautiously added dropwise with stirring, the resulting mixture was treated with an aqueous 10% solution of sodium hydroxide (100 cm3), and stirring was continued for a further 24 hours. Volatile material was then removed in vacuo and the residue was partitioned between water (100 cm3) and chloroform (200 cm3). The aqueous phase was re-extracted with chloroform (2×200 cm3), and the combined and dried (MgSO4) organic extracts were evaporated in vacuo to give an oil which was chromatographed on silica (Merck "MK 60.9385" [Trade Mark]) eluting with chloroform. Combination and evaporation of appropriate fractions afforded the title compound, m.p. 101°-103° (14.22 g). the reaction mixture was warmed to 50° for a further 3 hours After cooling in an ice-bath with stirring stirring was continued for a further 24 hours Volatile material was then removed in vacuo the residue was partitioned between water (100 cm3) and chloroform (200 cm3) The aqueous phase was re-extracted with chloroform (2×200 cm3) dried (MgSO4) organic extracts were evaporated in vacuo to give an oil which was chromatographed on silica (Merck "MK 60.9385" [Trade Mark]) eluting with chloroform Combination and evaporation of appropriate fractions