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

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The (2-amino-5-chloro-3-methylphenyl)methanol (10.8 g, 63.1 mmol) was dissolved in tetrahydrofuran (20 mL). Dichloromethane (50 mL) was added along with activated carbon (16.3 g). Activated manganese dioxide (16.8 g, 189 mmol) was added and the solution stirred at 40° C. for 16 h. The solution was cooled to room temperature and vacuum filtered through a celite. The solvent was removed at reduced pressure and the 2-amino-5-chloro-3-methylbenzaldehyde (7.90 g, 46.0 mmol) obtained by recrystallization from diethyl ether/hexanes (1:10, 100 mL). HRMS m/z 169.0280; calcd 169.0294. The solution was cooled to room temperature vacuum filtered through a celite The solvent was removed at reduced pressure

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

Procedure: The 2-amino-5-chloro-3-methylbenzoic acid (15.6 g, 84.3 mmol) was dissolved in tetrahydrofuran (200 ml) and cooled to 0° C. A solution of borane dimethylsulfide complex (16.8 mL, 16.8 mmol) was dissolved in tetrahydrofuran (40 mL) and added dropwise. The solution was kept at 0° C. for an additional 30 minutes and warmed to room temperature for 2 h and finally refluxed for 16 h. The solution was cooled to room temperature and methanol (10 mL) added slowly to control the gas evolution. The solution was stirred for 30 minutes at room temperature and 1 N hydrochloric acid added. The solution was stirred for 3 h and solvent removed to a volume of about 100 mL. Water (200 mL) was added and the solution extracted with diethylether (200 mL). The aqueous layer was collected, adjusted to pH=12 with 1N sodium hydroxide which formed a solid in the solution. The solid was collected, dissolved in ethyl acetate (100 mL), dried over sodium sulfate and solvent removed at reduced pressure. (2-Amino-5-chloro-3-methylphenyl)methanol (10.8 g, 63.1 mmol) was obtained as a light yellow solid (75% yield). HRMS m/z 172.0544; calcd for M+H 172.0524. added dropwise warmed to room temperature for 2 h finally refluxed for 16 h The solution was cooled to room temperature The solution was stirred for 3 h solvent removed to a volume of about 100 mL Water (200 mL) was added the solution extracted with diethylether (200 mL) The aqueous layer was collected formed a solid in the solution The solid was collected dissolved in ethyl acetate (100 mL) dried over sodium sulfate and solvent removed at reduced pressure

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

Procedure: The 2-amino-5-chloro-3-methylbenzoic acid (15.6 g, 84.3 mmol) was dissolved in tetrahydrofuran (200 ml) and cooled to 0° C. A solution of borane dimethylsulfide complex (16.8 mL, 16.8 mmol) was dissolved in tetrahydrofuran (40 mL) and added dropwise. The solution was kept at 0° C. for an additional 30 minutes and warmed to room temperature for 2 h and finally refluxed for 16 h. The solution was cooled to room temperature and methanol (10 mL) added slowly to control the gas evolution. The solution was stirred for 30 minutes at room temperature and 1 N hydrochloric acid added. The solution was stirred for 3 h and solvent removed to a volume of about 100 mL. Water (200 mL) was added and the solution extracted with diethylether (200 mL). The aqueous layer was collected, adjusted to pH=12 with 1N sodium hydroxide which formed a solid in the solution. The solid was collected, dissolved in ethyl acetate (100 mL), dried over sodium sulfate and solvent removed at reduced pressure. (2-Amino-5-chloro-3-methylphenyl)methanol (10.8 g, 63.1 mmol) was obtained as a light yellow solid (75% yield). HRMS m/z 172.0544; calcd for M+H 172.0524. added dropwise warmed to room temperature for 2 h finally refluxed for 16 h The solution was cooled to room temperature The solution was stirred for 3 h solvent removed to a volume of about 100 mL Water (200 mL) was added the solution extracted with diethylether (200 mL) The aqueous layer was collected formed a solid in the solution The solid was collected dissolved in ethyl acetate (100 mL) dried over sodium sulfate and solvent removed at reduced pressure

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The (2-amino-5-chloro-3-methylphenyl)methanol (10.8 g, 63.1 mmol) was dissolved in tetrahydrofuran (20 mL). Dichloromethane (50 mL) was added along with activated carbon (16.3 g). Activated manganese dioxide (16.8 g, 189 mmol) was added and the solution stirred at 40° C. for 16 h. The solution was cooled to room temperature and vacuum filtered through a celite. The solvent was removed at reduced pressure and the 2-amino-5-chloro-3-methylbenzaldehyde (7.90 g, 46.0 mmol) obtained by recrystallization from diethyl ether/hexanes (1:10, 100 mL). HRMS m/z 169.0280; calcd 169.0294. The solution was cooled to room temperature vacuum filtered through a celite The solvent was removed at reduced pressure

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

Procedure: The 2-amino-5-chloro-3-methylbenzoic acid (15.6 g, 84.3 mmol) was dissolved in tetrahydrofuran (200 ml) and cooled to 0° C. A solution of borane dimethylsulfide complex (16.8 mL, 16.8 mmol) was dissolved in tetrahydrofuran (40 mL) and added dropwise. The solution was kept at 0° C. for an additional 30 minutes and warmed to room temperature for 2 h and finally refluxed for 16 h. The solution was cooled to room temperature and methanol (10 mL) added slowly to control the gas evolution. The solution was stirred for 30 minutes at room temperature and 1 N hydrochloric acid added. The solution was stirred for 3 h and solvent removed to a volume of about 100 mL. Water (200 mL) was added and the solution extracted with diethylether (200 mL). The aqueous layer was collected, adjusted to pH=12 with 1N sodium hydroxide which formed a solid in the solution. The solid was collected, dissolved in ethyl acetate (100 mL), dried over sodium sulfate and solvent removed at reduced pressure. (2-Amino-5-chloro-3-methylphenyl)methanol (10.8 g, 63.1 mmol) was obtained as a light yellow solid (75% yield). HRMS m/z 172.0544; calcd for M+H 172.0524. added dropwise warmed to room temperature for 2 h finally refluxed for 16 h The solution was cooled to room temperature The solution was stirred for 3 h solvent removed to a volume of about 100 mL Water (200 mL) was added the solution extracted with diethylether (200 mL) The aqueous layer was collected formed a solid in the solution The solid was collected dissolved in ethyl acetate (100 mL) dried over sodium sulfate and solvent removed at reduced pressure