ethyl 5-amino-2-hydroxybenzoate

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

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

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

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

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

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

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

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl 2-hydroxy-5-aminobenzoate (31.8 g, 0.176 mole) was mixed with benzaldehyde (17.8 ml, 0.176 mole), and the mixture was heated to 100° C. for 10 minutes and subsequently cooled with ice-water. The resulting oil was recrystallized from 96% ethanol, with activated carbon, to give the title compound (31.6 g, 67%), m.p. 63°-65° C. Found (Calc. for C16H15NO3) C 71.18 (71.38), H 5.63 (5.58), N 5.22 (5.20). The resulting oil was recrystallized from 96% ethanol, with activated carbon

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl 2-hydroxy-5-aminobenzoate (33.0 g, 0.182 mole) was dissolved in acetic anhydride (33 ml) and heated to 100° C. for 10 minutes. The mixture was cooled to room temperature, water (33 ml) was added and the mixture was evaporated to dryness. The remaining material was recrystallized from water-ethanol (1:1) to give the title compound (26.4 g, 65%), m.p. 135°-136° C. Found (Calc. for C11H13NO4) C 59.12 (59.19), H 5.93 (5.83), N 6.30 (6.28). The mixture was cooled to room temperature the mixture was evaporated to dryness The remaining material was recrystallized from water-ethanol (1:1)

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

Procedure: 2-Hydroxy-5-aminobenzoic acid (40 g, 0.26 mole) was mixed with absolute ethanol (1 1) and concentrated sulphuric acid (40 ml) was slowly added after which the mixture was refluxed for 48 hours under nitrogen. The cooled reaction mixture was concentrated to about 350 ml, in vacuo, neutralized with 1M aqueous sodium hydrogen carbonate and extracted with ether (3×150 ml). The ethereal solution was washed with 1M sodium hydrogen carbonate (2×75 ml), water (2×75 ml), dried over anhydrous magnesium sulphate (25 g), activated carbon (2 g) was added, the solution was filtered and the filtrate evaporated to dryness. The product was recrystallized from water-ethanol (3:1) to give the title compound (10 g, 21%), m.p. 40°-43°. Found (Calc. for C9H11NO3) C 59.59 (59.66), H 6.13 (6.08), N 7.66 (7.73). was slowly added after which the mixture was refluxed for 48 hours under nitrogen The cooled reaction mixture was concentrated to about 350 ml, in vacuo extracted with ether (3×150 ml) The ethereal solution was washed with 1M sodium hydrogen carbonate (2×75 ml), water (2×75 ml) dried over anhydrous magnesium sulphate (25 g), activated carbon (2 g) was added the solution was filtered the filtrate evaporated to dryness The product was recrystallized from water-ethanol (3:1)

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

Procedure: A mixture of ethyl 4-chloro-6-ethoxy-7-methyl-1,8-naphthyridine-3-carboxylate (2.0 g), absolute ethanol (30 ml) and ethyl 5-aminosalicylate (1.23 g) was boiled under reflux for 1 hour. The mixture was cooled to ambient temperature and filtered to give a solid which was recrystallised from IMS to give ethyl 5-(6-ethoxy-3-ethoxycarbonyl-7-methyl-1,8-naphthyridin-4-ylamino)salicylate hydrochloride, m.p. 208°-210° C. under reflux for 1 hour filtered to give a solid which was recrystallised from IMS

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

Procedure: A mixture of 5-aminosalicylic acid (15 g), absolute ethanol (250 ml) and concentrated sulphuric acid (7.5 ml) was boiled under reflux with stirring for 8.5 hours. The reaction mixture was evaporated to dryness. Water (20 ml) was added to the residue and the mixture filtered. The filtrate was basified with saturated bicarbonate solution and the solid collected by filtration. The solid was extracted into dichloromethane and the extract evaporated to dryness. The residue was triturated with petroleum ether b.p. 40°-60° C. and filtered to give ethyl 5-aminosalicylate, m.p. 44° C. under reflux The reaction mixture was evaporated to dryness Water (20 ml) was added to the residue the mixture filtered the solid collected by filtration The solid was extracted into dichloromethane the extract evaporated to dryness The residue was triturated with petroleum ether b.p. 40°-60° C. filtered