methyl 2-amino-6-hydroxybenzoate

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

Procedure: Prepared by proceeding in a similar manner to Intermediate 6, starting from methyl 2-amino-6-hydroxybenzoate (prepared according to Comess et al, US2004 0167128) Prepared

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

Procedure: Prepared by proceeding in a similar manner to Intermediate 6, starting from methyl 2-amino-6-hydroxybenzoate (prepared according to Comess et al, US2004 0167128) Prepared

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

Procedure: Trimethylacetyl chloride (3.69 g) was added to a mixture of methyl 2-amino-6-hydroxybenzoate (prepared according to Comess et al, US2004 0167128, 3.99 g) and sodium bicarbonate (2.57 g) in ethyl acetate (77 mL) and water (18 mL). The reaction mixture was stirred at room temperature for 1 hour. A further amount of trimethylacetyl chloride (1.85 g) was added and the mixture was stirred for 1 hour. A further amount of trimethylacetyl chloride (0.920 g) was added and the mixture was stirred for 30 minutes. The mixture was diluted with ethyl acetate, the layers were separated and the organic layer was dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 5-25% to give methyl 2-(2,2-dimethylpropionylamino)-6-hydroxybenzoate (5.79 g) as a white solid. the mixture was stirred for 1 hour the mixture was stirred for 30 minutes the layers were separated the organic layer was dried (Na2SO4) filtered The filtrate was concentrated in vacuo the residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 5-25%

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

Procedure: Trimethylacetyl chloride (5.57 g) was added dropwise to a vigorously stirred mixture of methyl 2-amino-6-hydroxybenzoate (prepared according to Comess et al, US2004 0167128, 5.15 g) and sodium bicarbonate (7.76 g) in a mixture of water (40 mL) and ethyl acetate (100 mL) and the mixture was stirred for one hour. Further trimethylacetyl chloride (5.57 g) was added and the mixture stirred overnight. The organic layer was separated, dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo and the residue was triturated with pentane. The solid was collected by filtration and purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-25% to give methyl 2-(2,2-dimethyl-propionylamino)-6-hydroxy-benzoate (4.96 g) as a white solid. the mixture stirred overnight The organic layer was separated dried (Na2SO4) filtered The filtrate was concentrated in vacuo the residue was triturated with pentane The solid was collected by filtration purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-25%

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

Procedure: Trimethylacetyl chloride (3.69 g) was added to a mixture of methyl 2-amino-6-hydroxybenzoate (prepared according to Comess et al, US2004 0167128, 3.99 g) and sodium bicarbonate (2.57 g) in ethyl acetate (77 mL) and water (18 mL). The reaction mixture was stirred at room temperature for 1 hour. A further amount of trimethylacetyl chloride (1.85 g) was added and the mixture was stirred for 1 hour. A further amount of trimethylacetyl chloride (0.920 g) was added and the mixture was stirred for 30 minutes. The mixture was diluted with ethyl acetate, the layers were separated and the organic layer was dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 5-25% to give methyl 2-(2,2-dimethylpropionylamino)-6-hydroxybenzoate (5.79 g) as a white solid. the mixture was stirred for 1 hour the mixture was stirred for 30 minutes the layers were separated the organic layer was dried (Na2SO4) filtered The filtrate was concentrated in vacuo the residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 5-25%

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

Procedure: A solution of methyl 2-amino-6-hydroxybenzoate (prepared according to Comess et al, US2004 167128, 3.8 g) and sodium bicarbonate (2.52 g) in ethyl acetate (75 mL) and water (17.5 mL) was stirred at room temperature and pivaloyl chloride (3.51 g) was added dropwise. The resultant mixture was stirred at room temperature for 1 hour. A further amount of pivaloyl chloride (1.75 g) was added and the mixture was stirred at room temperature for 2.5 hours. A further amount of pivaloyl chloride (1 g) was added and the mixture was stirred at room temperature for 4 hours and 20 minutes. Ethyl acetate and saturated aqueous sodium bicarbonate solution were added and the layers were separated. The organic phase was washed with brine, dried (Na2SO4), filtered and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 5-25% to give methyl 2-tert-butylcarbonylamino-6-hydroxybenzoate (4.46 g) as a white solid. the mixture was stirred at room temperature for 4 hours and 20 minutes the layers were separated The organic phase was washed with brine dried (Na2SO4) filtered the filtrate was concentrated in vacuo The residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 5-25%

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

Procedure: A mixture of Example 386A (1.0 g, 5.6 mmol) and methanol (40 mL) was heated to reflux for 6 hours, concentrated, and purified on a silica gel column eluting with 30% ethyl acetate in hexanes to provide the desired product, 0.81 g, 86.6%. 1H NMR (DMSO-d6) δ 3.88 (s, 3H), 5.95 (d, 1H), 6.20 (d, 1H), 6.34 (s, 214), 7.02 (t, 1H), 10.88 (s, 1H); MS (DCI/NH3): m/e 168 (M+H)+. to reflux for 6 hours concentrated purified on a silica gel column eluting with 30% ethyl acetate in hexanes

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

Procedure: Prepared by proceeding in a similar manner to Intermediate 6, starting from methyl 2-amino-6-hydroxybenzoate (prepared according to Comess et al, US2004 0167128) Prepared

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

Procedure: Trimethylacetyl chloride (3.69 g) was added to a mixture of methyl 2-amino-6-hydroxybenzoate (prepared according to Comess et al, US2004 0167128, 3.99 g) and sodium bicarbonate (2.57 g) in ethyl acetate (77 mL) and water (18 mL). The reaction mixture was stirred at room temperature for 1 hour. A further amount of trimethylacetyl chloride (1.85 g) was added and the mixture was stirred for 1 hour. A further amount of trimethylacetyl chloride (0.920 g) was added and the mixture was stirred for 30 minutes. The mixture was diluted with ethyl acetate, the layers were separated and the organic layer was dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 5-25% to give methyl 2-(2,2-dimethylpropionylamino)-6-hydroxybenzoate (5.79 g) as a white solid. the mixture was stirred for 1 hour the mixture was stirred for 30 minutes the layers were separated the organic layer was dried (Na2SO4) filtered The filtrate was concentrated in vacuo the residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 5-25%

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

Procedure: Trimethylacetyl chloride (5.57 g) was added dropwise to a vigorously stirred mixture of methyl 2-amino-6-hydroxybenzoate (prepared according to Comess et al, US2004 0167128, 5.15 g) and sodium bicarbonate (7.76 g) in a mixture of water (40 mL) and ethyl acetate (100 mL) and the mixture was stirred for one hour. Further trimethylacetyl chloride (5.57 g) was added and the mixture stirred overnight. The organic layer was separated, dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo and the residue was triturated with pentane. The solid was collected by filtration and purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-25% to give methyl 2-(2,2-dimethyl-propionylamino)-6-hydroxy-benzoate (4.96 g) as a white solid. the mixture stirred overnight The organic layer was separated dried (Na2SO4) filtered The filtrate was concentrated in vacuo the residue was triturated with pentane The solid was collected by filtration purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-25%