2-aminophenol;hydrochloride

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

Procedure: In a preferred embodiment of the present invention, in step (a), the 2-aminophenol solution may be maintained at a pH of 2-5 while hydrochloride gas is added thereto, and as a result, 2-aminophenol hydrochloride can be obtained in solid form. In step (b), the solution of 2-aminophenol hydrochloride in ethanol may be reacted with isopentyl nitrite at about −5° C. to make the nitramide intermediate. In step (c), the solution of the intermediate in ethanol may be added slowly to the ethanol solution containing para-toluenesulfonic acid (PTSA or TsOH) and tin chloride (SnCl2) at low temperature (−5° C.), thereby obtaining 2-hydrazinylphenol tosylate. is added

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

Procedure: In a preferred embodiment of the present invention, in step (a), the 2-aminophenol solution may be maintained at a pH of 2-5 while hydrochloride gas is added thereto, and as a result, 2-aminophenol hydrochloride can be obtained in solid form. In step (b), the solution of 2-aminophenol hydrochloride in ethanol may be reacted with isopentyl nitrite at about −5° C. to make the nitramide intermediate. In step (c), the solution of the intermediate in ethanol may be added slowly to the ethanol solution containing para-toluenesulfonic acid (PTSA or TsOH) and tin chloride (SnCl2) at low temperature (−5° C.), thereby obtaining 2-hydrazinylphenol tosylate. is added

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

Procedure: In the present invention, the starting material 2-hydrazinylphenol may be in tosylate form. The 2-hydrazinylphenol in tosylate form can be prepared by a process comprising the steps of: (a) dissolving 2-aminophenol in methanol and adding hydrochloride gas thereto to obtain 2-aminophenol hydrochloride (HCl); (b) dissolving the 2-aminophenol hydrochloride in ethanol and adding isopentyl nitrite thereto to make a nitramide intermediate; and (c) adding the intermediate to an ethanol solution containing para-toluenesulfonic acid (PTSA or TsOH) and tin chloride (SnCl2), thereby obtaining 2-hydrazinylphenol tosylate.

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

Procedure: Diisobutylaluminum (100 mL of 1.0 M, 100 mmol) was added dropwise to a solution of dimethyl 2-methylbutanedioate (7.6 g, 48 mmol) in dichloromethane (15 mL) at −78° C., and the solution was stirred for 1 h. A suspension of 2-aminophenol HCl salt (6.6 g, 45 mmol) in water (110 mL) was added initially dropwise with vigorous stirring, then in small portions. About midway through the addition, the cooling bath was removed to help facilitate stirring. The mixture was stirred vigourously at room temperature overnight, then filtered over celite and the filter cake was washed several times with dichloromethane. The filtrate was separated, and the aqueous layer was extracted with dichloromethane (2×20 mL). The combined organics were washed with brine (50 mL), dried over MgSO4, concentrated and purified by column chromatography (0-40% EtOAc/hexane) to give 2-(3-methylpyrrol-1-yl)phenol (3.7 g, 48%) as a yellow oil. ESI-MS m/z calc. 173.2. found 174.3 (M+1)+; Retention time: 1.51 minutes (3 min run). was added initially dropwise with vigorous stirring About midway through the addition the cooling bath was removed to help facilitate stirring The mixture was stirred vigourously at room temperature overnight filtered over celite the filter cake was washed several times with dichloromethane The filtrate was separated the aqueous layer was extracted with dichloromethane (2×20 mL) The combined organics were washed with brine (50 mL) dried over MgSO4 concentrated purified by column chromatography (0-40% EtOAc/hexane)

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

Procedure: Diisobutylaluminum (100 mL of 1.0 M, 100 mmol) was added dropwise to a solution of dimethyl 2-methylbutanedioate (7.6 g, 48 mmol) in dichloromethane (15 mL) at −78° C., and the solution was stirred for 1 h. A suspension of 2-aminophenol HCl salt (6.6 g, 45 mmol) in water (110 mL) was added initially dropwise with vigorous stirring, then in small portions. About midway through the addition, the cooling bath was removed to help facilitate stirring. The mixture was stirred vigourously at room temperature overnight, then filtered over celite and the filter cake was washed several times with dichloromethane. The filtrate was separated, and the aqueous layer was extracted with dichloromethane (2×20 mL). The combined organics were washed with brine (50 mL), dried over MgSO4, concentrated and purified by column chromatography (0-40% EtOAc/hexane) to give 2-(3-methylpyrrol-1-yl)phenol (3.7 g, 48%) as a yellow oil. ESI-MS m/z calc. 173.2, found 174.3 (M+1)+; Retention time: 1.51 minutes (3 min run). was added initially dropwise with vigorous stirring About midway through the addition the cooling bath was removed to help facilitate stirring The mixture was stirred vigourously at room temperature overnight filtered over celite the filter cake was washed several times with dichloromethane The filtrate was separated the aqueous layer was extracted with dichloromethane (2×20 mL) The combined organics were washed with brine (50 mL) dried over MgSO4 concentrated purified by column chromatography (0-40% EtOAc/hexane)

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

Procedure: Diisobutylaluminum (100 mL of 1.0 M, 100 mmol) was added dropwise to a solution of dimethyl 2-methylbutanedioate (7.6 g, 48 mmol) in dichloromethane (15 mL) at −78° C., and the solution was stirred for 1 h. A suspension of 2-aminophenol HCl salt (6.6 g, 45 mmol) in water (110 mL) was added initially dropwise with vigorous stirring, then in small portions. About midway through the addition, the cooling bath was removed to help facilitate stirring. The mixture was stirred vigourously at room temperature overnight, then filtered over celite and the filter cake was washed several times with dichloromethane. The filtrate was separated, and the aqueous layer was extracted with dichloromethane (2×20 mL). The combined organics were washed with brine (50 mL), dried over MgSO4, concentrated and purified by column chromatography (0-40% EtOAc/hexane) to give 2-(3-methylpyrrol-1-yl)phenol (3.7 g, 48%) as a yellow oil. ESI-MS m/z calc. 173.2, found 174.3 (M+1)+; Retention time: 1.51 minutes (3 min run). was added initially dropwise with vigorous stirring About midway through the addition the cooling bath was removed to help facilitate stirring The mixture was stirred vigourously at room temperature overnight filtered over celite the filter cake was washed several times with dichloromethane The filtrate was separated the aqueous layer was extracted with dichloromethane (2×20 mL) The combined organics were washed with brine (50 mL) dried over MgSO4 concentrated purified by column chromatography (0-40% EtOAc/hexane)

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

Procedure: In a preferred embodiment of the present invention, in step (a), the 2-aminophenol solution may be maintained at a pH of 2-5 while hydrochloride gas is added thereto, and as a result, 2-aminophenol hydrochloride can be obtained in solid form. In step (b), the solution of 2-aminophenol hydrochloride in ethanol may be reacted with isopentyl nitrite at about −5° C. to make the nitramide intermediate. In step (c), the solution of the intermediate in ethanol may be added slowly to the ethanol solution containing para-toluenesulfonic acid (PTSA or TsOH) and tin chloride (SnCl2) at low temperature (−5° C.), thereby obtaining 2-hydrazinylphenol tosylate. is added

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

Procedure: In the present invention, the starting material 2-hydrazinylphenol may be in tosylate form. The 2-hydrazinylphenol in tosylate form can be prepared by a process comprising the steps of: (a) dissolving 2-aminophenol in methanol and adding hydrochloride gas thereto to obtain 2-aminophenol hydrochloride (HCl); (b) dissolving the 2-aminophenol hydrochloride in ethanol and adding isopentyl nitrite thereto to make a nitramide intermediate; and (c) adding the intermediate to an ethanol solution containing para-toluenesulfonic acid (PTSA or TsOH) and tin chloride (SnCl2), thereby obtaining 2-hydrazinylphenol tosylate.