4-[(1R)-2-(tert-butylamino)-1-hydroxyethyl]-2-(hydroxymethyl)phenol

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

Procedure: In a 25 ml reactor equipped with a condenser, thermometer, and mechanical stirrer loaded at room temperature levalbuterol HCl (1.2 g) and absolute ethanol (15 ml). The solution was warmed to 45° C. to 50° to obtain a solution. The solution was cooled to room temperature and after MTBE (8.75 ml) was added. The solution was stirred at 15° C. for 2 hours to obtain a suspension. The solid was collected by filtration and washed with MTBE (3 ml) to obtain levalbuterol Polymorph A (0.8 g). In a 25 ml reactor equipped with a condenser thermometer, and mechanical stirrer loaded at room temperature The solution was warmed to 45° C. to 50° to obtain a solution to obtain a suspension The solid was collected by filtration washed with MTBE (3 ml)

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

Procedure: In a 25 ml reactor equipped with a condenser, thermometer, and mechanical stirrer loaded at room temperature levalbuterol HCl (1 g) and absolute ethanol (19 ml). The solution was warmed to 45° C. to 50° C. to obtain a solution. The solution was cooled to room temperature and after MTBE (9.5 ml) was added. The solution was stirred at room temperature for 1 hour to obtain a suspension. The solid was collected by filtration and washed with MTBE (3 ml) to obtain levalbuterol Polymorph A (0.6 g). In a 25 ml reactor equipped with a condenser thermometer, and mechanical stirrer loaded at room temperature The solution was warmed to 45° C. to 50° C. to obtain a solution to obtain a suspension The solid was collected by filtration washed with MTBE (3 ml)

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

Procedure: In a 25 ml reactor equipped with a condenser, thermometer, and mechanical stirrer loaded at room temperature levalbuterol HCl (1 g) and absolute ethanol (19 ml). The solution was warmed to 45° C. to 50° C. to obtain a solution. The solution was cooled to room temperature and after MTBE (9.5 ml) was added. The solution was stirred at room temperature for 1 hour to obtain a suspension. The solid was collected by filtration and washed with MTBE (3 ml) to obtain levalbuterol Polymorph A (0.6 g). In a 25 ml reactor equipped with a condenser thermometer, and mechanical stirrer loaded at room temperature The solution was warmed to 45° C. to 50° C. to obtain a solution to obtain a suspension The solid was collected by filtration washed with MTBE (3 ml)

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

Procedure: Several patents report synthetic routes using enantiomeric separation, however, the synthetic routes result in low yields of the enantiomerically pure product. Optically pure levalbuterol was synthesized by the borane-methylsulfide reduction of the enantiomerically pure precursor (Formula 2) as described in U.S. Pat. No. 5,399,765. The reaction dissolved a mixture of enantiomers of methyl 5-[2-[(1,1-dimethylethyl)amino]-1-hydroxyethyl]-2-hydroxybenzoate and a chiral acid selected from (−)-di-toluoyl-L-tartaric acid and (+)-di-toluoyl-D-tartaric acid in methanol, upon cooling one stereoisomer crystallized, which was separated, and recrystallized as a diastereomer from methanol, the diastereomer was separated, treated with base, and upon reduction formed optically active levalbuterol. separation however, the synthetic routes result in low yields of the enantiomerically pure product The reaction dissolved upon cooling one stereoisomer crystallized, which was separated recrystallized as a diastereomer from methanol the diastereomer was separated treated with base