methyl 2-chloro-4-(hydroxymethyl)benzoate

Conditions: temp:27.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl 2-chloro-4-(hydroxymethyl)benzoate (350 mg, 1.7 mmol) in and manganese oxide (756 mg, 30.9 mmol) in dichloromethane (10 mL) was stirred at 27° C. for 6 hours. The mixture was filtered and evaporated in vacuo to give Intermediate 75 (210 mg, 61%). The mixture was filtered evaporated in vacuo

Conditions: temp:76.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-chloro-4-(methoxycarbonyl)benzoic acid (400 mg, 1.9 mmol) in anhydrous THF (15 mL) was added Borane methyl sulfide complex (10 M, 0.56 mL, 5.6 mmol). The resulting solution was heated at 76° C. for 6 hours. After being cooled, the mixture was slowly poured into water (40 mL) at −10° C., then followed a standard aqueous/EtOAc workup procedure to give crude product (350 mg, yield 94%). After being cooled

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

Procedure: A solution of 2-chloro-4-(hydroxymethyl)benzoic acid, methyl ester (11.09 g, 55.3 mmol), diphenylphosphoryl azide (22.58 g, 82.0 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (8.57 g, 56.3 mmol) in tetrahydrofuran was stirred overnight at room temperature. Silica gel was added and the solvent was evaporated. The residue was chromatographed (10% ethyl acetate/hexanes) to give 4-(azidomethyl)-2-chlorobenzoic acid, methyl ester (12.17 g, 98%) as a white solid. Silica gel was added the solvent was evaporated The residue was chromatographed (10% ethyl acetate/hexanes)

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

Procedure: Borane-methyl sulfide complex (10 M; 10 mL, 100 mmol) was added to a solution of 2-chloro-1,4-benzenedicarboxylic acid, 1-methyl ester (Example 1; 11.98 g, 55.8 mmol) in tetrahydrofuran (100 mL). The solution was heated at reflux for 2 h and then allowed to stand at room temperature overnight. It was poured into water and ethyl acetate (200 mL each). The layers were separated and the aqueous layer was extracted with ethyl acetate (100 mL). The combined organic layers were washed with brine (200 mL), dried (MgSO4), filtered, and evaporated to give 2-chloro-4-(hydroxymethyl)benzoic acid, methyl ester (11.09 g, 99%) as a colorless oil. The solution was heated at reflux for 2 h The layers were separated the aqueous layer was extracted with ethyl acetate (100 mL) The combined organic layers were washed with brine (200 mL) dried (MgSO4) filtered evaporated

Conditions: temp:27.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl 2-chloro-4-(hydroxymethyl)benzoate (350 mg, 1.7 mmol) in and manganese oxide (756 mg, 30.9 mmol) in dichloromethane (10 mL) was stirred at 27° C. for 6 hours. The mixture was filtered and evaporated in vacuo to give Intermediate 75 (210 mg, 61%). The mixture was filtered evaporated in vacuo

Conditions: temp:76.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-chloro-4-(methoxycarbonyl)benzoic acid (400 mg, 1.9 mmol) in anhydrous THF (15 mL) was added Borane methyl sulfide complex (10 M, 0.56 mL, 5.6 mmol). The resulting solution was heated at 76° C. for 6 hours. After being cooled, the mixture was slowly poured into water (40 mL) at −10° C., then followed a standard aqueous/EtOAc workup procedure to give crude product (350 mg, yield 94%). After being cooled

Conditions: temp:76.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-chloro-4-(methoxycarbonyl)benzoic acid (400 mg, 1.9 mmol) in anhydrous THF (15 mL) was added Borane methyl sulfide complex (10 M, 0.56 mL, 5.6 mmol). The resulting solution was heated at 76° C. for 6 hours. After being cooled, the mixture was slowly poured into water (40 mL) at −10° C., then followed a standard aqueous/EtOAc workup procedure to give crude product (350 mg, yield 94%). After being cooled

Conditions: temp:27.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl 2-chloro-4-(hydroxymethyl)benzoate (350 mg, 1.7 mmol) in and manganese oxide (756 mg, 30.9 mmol) in dichloromethane (10 mL) was stirred at 27° C. for 6 hours. The mixture was filtered and evaporated in vacuo to give Intermediate 75 (210 mg, 61%). The mixture was filtered evaporated in vacuo

Conditions: temp:76.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-chloro-4-(methoxycarbonyl)benzoic acid (400 mg, 1.9 mmol) in anhydrous THF (15 mL) was added Borane methyl sulfide complex (10 M, 0.56 mL, 5.6 mmol). The resulting solution was heated at 76° C. for 6 hours. After being cooled, the mixture was slowly poured into water (40 mL) at −10° C., then followed a standard aqueous/EtOAc workup procedure to give crude product (350 mg, yield 94%). After being cooled

Conditions: temp:27.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl 2-chloro-4-(hydroxymethyl)benzoate (350 mg, 1.7 mmol) in and manganese oxide (756 mg, 30.9 mmol) in dichloromethane (10 mL) was stirred at 27° C. for 6 hours. The mixture was filtered and evaporated in vacuo to give Intermediate 75 (210 mg, 61%). The mixture was filtered evaporated in vacuo

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

Procedure: A solution of 2-chloro-4-(hydroxymethyl)benzoic acid, methyl ester (11.09 g, 55.3 mmol), diphenylphosphoryl azide (22.58 g, 82.0 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (8.57 g, 56.3 mmol) in tetrahydrofuran was stirred overnight at room temperature. Silica gel was added and the solvent was evaporated. The residue was chromatographed (10% ethyl acetate/hexanes) to give 4-(azidomethyl)-2-chlorobenzoic acid, methyl ester (12.17 g, 98%) as a white solid. Silica gel was added the solvent was evaporated The residue was chromatographed (10% ethyl acetate/hexanes)

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

Procedure: Borane-methyl sulfide complex (10 M; 10 mL, 100 mmol) was added to a solution of 2-chloro-1,4-benzenedicarboxylic acid, 1-methyl ester (Example 1; 11.98 g, 55.8 mmol) in tetrahydrofuran (100 mL). The solution was heated at reflux for 2 h and then allowed to stand at room temperature overnight. It was poured into water and ethyl acetate (200 mL each). The layers were separated and the aqueous layer was extracted with ethyl acetate (100 mL). The combined organic layers were washed with brine (200 mL), dried (MgSO4), filtered, and evaporated to give 2-chloro-4-(hydroxymethyl)benzoic acid, methyl ester (11.09 g, 99%) as a colorless oil. The solution was heated at reflux for 2 h The layers were separated the aqueous layer was extracted with ethyl acetate (100 mL) The combined organic layers were washed with brine (200 mL) dried (MgSO4) filtered evaporated