tert-butyl 3-amino-4-hydroxybenzoate

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

Procedure: To a solution of 4-aminophenol (10.9 g, 100 mmol) in THF (150 mL) cooled in an ice bath was added di-tert-butyl-dicarbonate (21.8 g, 100 mmol) followed by diisopropylethylamine (17.4 mL, 100 mmol). The mixture was stirred at room temperature overnight and concentrated. The residue was taken up in ethyl acetate and the solution was washed with brine, dried (MgSO4), and concentrated. Purification on a silica gel column eluting with 5% methanol/40% ethyl acetate hexane gave 4Boc-aminophenol (20.1 g, 96%). MS(NH3—CI): (M+NH3+H)=227. concentrated the solution was washed with brine dried (MgSO4) concentrated Purification on a silica gel column eluting with 5% methanol/40% ethyl acetate hexane

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

Procedure: To a stirred solution of tert-butyl 4-hydroxy-3-aminobenzoate (3 g, 14.35 mmol) in methanol (20 mL) sodium hydrogen carbonate (1.5 g) was added and a solution of methyl-4-bromo crotonate (3 mL, 17 mmol) in methanol (5 mL) was added dropwise in 30 minutes and the resulting suspension was stirred 4 h at room temperature. The reaction mixture was concentrated in vacuo and taken up with ethyl acetate (250 mL) and water (300 mL). The organic phase was separated and the aqueous phase was extracted with more ethyl acetate (2×250 mL). The combined extracts were dried (Na2SO4) evaporated and the resulting oil dissolved in ethanol (25 mL), potassium carbonate (1 g) was added and the resulting suspension was stirred 4 h at room temperature. The reaction mixture was evaporated in vacuo and the resulting oil was diluted with dichloromethane (150 mL) and washed with water (3×100 mL), the organic solution was then extracted whit hydrochloric acid 1N (150 mL) and separated, the aqueous solution was neutralized with 1N sodium hydroxide and extracted with ethyl acetate (3×150 mL). The combined extract were dried (Na2SO4) evaporated to dryness in vacuo, the resulting crude was purified by flash chromatography on silica gel (n-hexane/ethyl acetate 3:1) to afford tert-butyl 2-(2-methoxy-2-oxoethyl)-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate (5.4 g) as a white solid. The reaction mixture was concentrated in vacuo The organic phase was separated the aqueous phase was extracted with more ethyl acetate (2×250 mL) The combined extracts were dried (Na2SO4) evaporated the resulting oil dissolved in ethanol (25 mL) potassium carbonate (1 g) was added the resulting suspension was stirred 4 h at room temperature The reaction mixture was evaporated in vacuo the resulting oil was diluted with dichloromethane (150 mL) washed with water (3×100 mL) the organic solution was then extracted whit hydrochloric acid 1N (150 mL) separated extracted with ethyl acetate (3×150 mL) The combined extract were dried (Na2SO4) evaporated to dryness in vacuo the resulting crude was purified by flash chromatography on silica gel (n-hexane/ethyl acetate 3:1)

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

Procedure: To a stirred solution of tert-butyl 4-hydroxy-3-aminobenzoate (3 g, 14.35 mmol) in methanol (20 mL) sodium hydrogen carbonate (1.5 g) was added and a solution of methyl-4-bromo crotonate (3 mL, 17 mmol) in methanol (5 mL) was added dropwise in 30 minutes and the resulting suspension was stirred 4 h at room temperature. The reaction mixture was concentrated in vacuo and taken up with ethyl acetate (250 mL) and water (300 mL). The organic phase was separated and the aqueous phase was extracted with more ethyl acetate (2×250 mL). The combined extracts were dried (Na2SO4) evaporated and the resulting oil dissolved in ethanol (25 mL), potassium carbonate (1 g) was added and the resulting suspension was stirred 4 h at room temperature. The reaction mixture was evaporated in vacuo and the resulting oil was diluted with dichloromethane (150 mL) and washed with water (3×100 mL), the organic solution was then extracted whit hydrochloric acid 1N (150 mL) and separated, the aqueous solution was neutralized with 1N sodium hydroxide and extracted with ethyl acetate (3×150 mL). The combined extract were dried (Na2SO4) evaporated to dryness in vacuo, the resulting crude was purified by flash chromatography on silica gel (n-hexane/ethyl acetate 3:1) to afford tert-butyl 2-(2-methoxy-2-oxoethyl)-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate (5.4 g) as a white solid. The reaction mixture was concentrated in vacuo The organic phase was separated the aqueous phase was extracted with more ethyl acetate (2×250 mL) The combined extracts were dried (Na2SO4) evaporated the resulting oil dissolved in ethanol (25 mL) potassium carbonate (1 g) was added the resulting suspension was stirred 4 h at room temperature The reaction mixture was evaporated in vacuo the resulting oil was diluted with dichloromethane (150 mL) washed with water (3×100 mL) the organic solution was then extracted whit hydrochloric acid 1N (150 mL) separated extracted with ethyl acetate (3×150 mL) The combined extract were dried (Na2SO4) evaporated to dryness in vacuo the resulting crude was purified by flash chromatography on silica gel (n-hexane/ethyl acetate 3:1)

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

Procedure: To a solution of tert-butyl 4-hydroxy-3-nitrobenzoate (4.4 g, 18.4 mmol) in methanol (50 mL), 10% Pd/C (200 mg) was added and the resulting suspension was hydrogenated at 50 psi for 4 hours. After filtering under a pad of celite, methanol was removed in vacuo to obtain the title compound as a greenish powder (3.5 g, 95%). After filtering under a pad of celite, methanol was removed in vacuo

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

Procedure: To a solution of 4-aminophenol (10.9 g, 100 mmol) in THF (150 mL) cooled in an ice bath was added di-tert-butyl-dicarbonate (21.8 g, 100 mmol) followed by diisopropylethylamine (17.4 mL, 100 mmol). The mixture was stirred at room temperature overnight and concentrated. The residue was taken up in ethyl acetate and the solution was washed with brine, dried (MgSO4), and concentrated. Purification on a silica gel column eluting with 5% methanol/40% ethyl acetate hexane gave 4Boc-aminophenol (20.1 g, 96%). MS(NH3—CI): (M+NH3+H)=227. concentrated the solution was washed with brine dried (MgSO4) concentrated Purification on a silica gel column eluting with 5% methanol/40% ethyl acetate hexane

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

Procedure: To a solution of 4-aminophenol (10.9 g, 100 mmol) in THF (150 mL) cooled in an ice bath was added di-tert-butyl-dicarbonate (21.8 g, 100 mmol) followed by diisopropylethylamine (17.4 mL, 100 mmol). The mixture was stirred at room temperature overnight and concentrated. The residue was taken up in ethyl acetate and the solution was washed with brine, dried (MgSO4), and concentrated. Purification on a silica gel column eluting with 5% methanol/40% ethyl acetate hexane gave 4Boc-aminophenol (20.1 g, 96%). MS(NH3—CI): (M+NH3+H)=227. concentrated the solution was washed with brine dried (MgSO4) concentrated Purification on a silica gel column eluting with 5% methanol/40% ethyl acetate hexane

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

Procedure: To a solution of 4-aminophenol (10.9 g, 100 mmol) in THF (150 mL) cooled in an ice bath was added di-tert-butyl-dicarbonate (21.8 g, 100 mmol) followed by diisopropylethylamine (17.4 mL, 100 mmol). The mixture was stirred at room temperature overnight and concentrated. The residue was taken up in ethyl acetate and the solution was washed with brine, dried (MgSO4), and concentrated. Purification on a silica gel column eluting with 5% methanol/40% ethyl acetate/hexane gave 4-Boc-aminophenol (20.1 g, 96%). MS(NH3-CI): (M+NH3+H)=227. concentrated the solution was washed with brine dried (MgSO4) concentrated Purification on a silica gel column eluting with 5% methanol/40% ethyl acetate/hexane

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

Procedure: To a solution of 4-aminophenol (10.9 g, 100 mmol) in THF (150 mL) cooled in an ice bath was added di-tert-butyl-dicarbonate (21.8 g, 100 mmol) followed by diisopropylethylamine (17.4 mL, 100 mmol). The mixture was stirred at room temperature overnight and concentrated. The residue was taken up in ethyl acetate and the solution was washed with brine, dried (MgSO4), and concentrated. Purification on a silica gel column eluting with 5% methanol/40% ethyl acetate/hexane gave 4-Boc-aminophenol (20.1 g, 96%). MS(NH3-CI): (M+NH3+H)=227. concentrated the solution was washed with brine dried (MgSO4) concentrated Purification on a silica gel column eluting with 5% methanol/40% ethyl acetate/hexane

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

Procedure: To a stirred solution of tert-butyl 4-hydroxy-3-aminobenzoate (3 g, 14.35 mmol) in methanol (20 mL) sodium hydrogen carbonate (1.5 g) was added and a solution of methyl-4-bromo crotonate (3 mL, 17 mmol) in methanol (5 mL) was added dropwise in 30 minutes and the resulting suspension was stirred 4 h at room temperature. The reaction mixture was concentrated in vacuo and taken up with ethyl acetate (250 mL) and water (300 mL). The organic phase was separated and the aqueous phase was extracted with more ethyl acetate (2×250 mL). The combined extracts were dried (Na2SO4) evaporated and the resulting oil dissolved in ethanol (25 mL), potassium carbonate (1 g) was added and the resulting suspension was stirred 4 h at room temperature. The reaction mixture was evaporated in vacuo and the resulting oil was diluted with dichloromethane (150 mL) and washed with water (3×100 mL), the organic solution was then extracted whit hydrochloric acid 1N (150 mL) and separated, the aqueous solution was neutralized with 1N sodium hydroxide and extracted with ethyl acetate (3×150 mL). The combined extract were dried (Na2SO4) evaporated to dryness in vacuo, the resulting crude was purified by flash chromatography on silica gel (n-hexane/ethyl acetate 3:1) to afford tert-butyl 2-(2-methoxy-2-oxoethyl)-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate (5.4 g) as a white solid. The reaction mixture was concentrated in vacuo The organic phase was separated the aqueous phase was extracted with more ethyl acetate (2×250 mL) The combined extracts were dried (Na2SO4) evaporated the resulting oil dissolved in ethanol (25 mL) potassium carbonate (1 g) was added the resulting suspension was stirred 4 h at room temperature The reaction mixture was evaporated in vacuo the resulting oil was diluted with dichloromethane (150 mL) washed with water (3×100 mL) the organic solution was then extracted whit hydrochloric acid 1N (150 mL) separated extracted with ethyl acetate (3×150 mL) The combined extract were dried (Na2SO4) evaporated to dryness in vacuo the resulting crude was purified by flash chromatography on silica gel (n-hexane/ethyl acetate 3:1)

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

Procedure: To a solution of tert-butyl 4-hydroxy-3-nitrobenzoate (4.4 g, 18.4 mmol) in methanol (50 mL), 10% Pd/C (200 mg) was added and the resulting suspension was hydrogenated at 50 psi for 4 hours. After filtering under a pad of celite, methanol was removed in vacuo to obtain the title compound as a greenish powder (3.5 g, 95%). After filtering under a pad of celite, methanol was removed in vacuo