methyl 3-chloro-5-(hydroxymethyl)benzoate

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of dimethyl 5-chloroisophthalate (10.0 g, 43.7 mmol, Astatech) in methanol (50 mL) and methylene chloride (50 mL) at 0° C. was added sodium borohydride (5.5 g, 140 mmol, Aldrich). The reaction was allowed to gradually reach room temperature and stir for 1 hour. Additional portions of sodium borohydride (0.50 g, 13 mmol) were added at 2 hours and 3 hours. The reaction mixture was cooled to 0° C. and the reaction was quenched with water. The layers were separated and the aqueous layer was extracted with three portions of DCM. The combined organic extracts were dried over sodium sulfate, filtered and concentrated. The product was purified by flash chromatography, eluting with a gradient from 0-25% EtOAc in hexanes. Yield: (4.51 g, 51%). was allowed to gradually reach room temperature the reaction was quenched with water The layers were separated the aqueous layer was extracted with three portions of DCM The combined organic extracts were dried over sodium sulfate filtered concentrated The product was purified by flash chromatography eluting with a gradient from 0-25% EtOAc in hexanes

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

Procedure: In a 3 liter 3-necked round-bottom flask equipped with mechanical stirrer and nitrogen inlet was placed 5-chloroisophthalic acid monomethyl ester (29.4 g). Borane tetrahydrofuran complex in tetrahydrofuran solution (1M, 280 ml) was then added to the flask dropwise at room temperature. The resulting solution was stirred at room temperature overnight. The reaction mixture was poured into saturated aqueous ammonium chloride solution (750 ml) and extracted with ethyl acetate (3×500 ml). The combined organic layers were agitated with 2% aqueous hydrochloric acid, washed with water, dried and the solvent eliminated in the rotavap yielding 29.4 g of 3-chloro-5-hydroxymethyl benzoic acid methyl ester as a clear oil. In a 3 liter 3-necked round-bottom flask equipped with mechanical stirrer and nitrogen inlet extracted with ethyl acetate (3×500 ml) The combined organic layers were agitated with 2% aqueous hydrochloric acid washed with water dried

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of dimethyl 5-chloroisophthalate (10.0 g, 43.7 mmol, Astatech) in methanol (50 mL) and methylene chloride (50 mL) at 0° C. was added sodium borohydride (5.5 g, 140 mmol, Aldrich). The reaction was allowed to gradually reach room temperature and stir for 1 hour. Additional portions of sodium borohydride (0.50 g, 13 mmol) were added at 2 hours and 3 hours. The reaction mixture was cooled to 0° C. and the reaction was quenched with water. The layers were separated and the aqueous layer was extracted with three portions of DCM. The combined organic extracts were dried over sodium sulfate, filtered and concentrated. The product was purified by flash chromatography, eluting with a gradient from 0-25% EtOAc in hexanes. Yield: (4.51 g, 51%). was allowed to gradually reach room temperature the reaction was quenched with water The layers were separated the aqueous layer was extracted with three portions of DCM The combined organic extracts were dried over sodium sulfate filtered concentrated The product was purified by flash chromatography eluting with a gradient from 0-25% EtOAc in hexanes