1-(3-amino-2-hydroxy-4-phenylmethoxyphenyl)ethanone

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

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

Procedure: 28 g (0.15 mol) 2-bromo-2-methyl-propionyl chloride are added dropwise to 25.7 g (0.10 mol) 1-(3-amino-4-benzyloxy-2-hydroxy-phenyl)-ethanone and 41 g (0.30 mol) potassium carbonate in 215 mL acetonitrile. After 8 hours stirring at reflux temperature the solid is filtered off, the filtrate is evaporated down and the residue is crystallised from ethanol. Yield: 11.2 g (35%); melting range=124-126° C. at reflux temperature the solid is filtered off the filtrate is evaporated down the residue is crystallised from ethanol

Conditions: temp:92.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 41 mL phenyl chloroformate are added dropwise to a solution of 47 g (183 mmol) 1-(3-amino-4-benzyloxy-2-hydroxy-phenyl)-ethanone (known from U.S. Pat. No. 4,460,581) in 135 mL pyridine, whereupon the temperature rises to 75° C. The mixture is stirred for 4 hours at 90-95° C., poured onto ice and acidified with hydrochloric acid. The precipitated solid is suction filtered, washed with diethyl ether and heated in 500 mL 95% acetonitrile for 30 minutes at reflux temperature. After cooling the solid is filtered off and washed with acetonitrile and diethyl ether. rises to 75° C poured onto ice filtered washed with diethyl ether heated in 500 mL 95% acetonitrile for 30 minutes at reflux temperature After cooling the solid is filtered off washed with acetonitrile and diethyl ether

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

Procedure: 2-Chloroacetyl chloride (1.77 mL) was added dropwise to a stirred mixture of 1-(3-amino-4-(benzyloxy)-2-hydroxyphenyl)ethanone (5.2 g) and sodium hydrogen carbonate (3.74 g) in DMF (30 mL) and then stirred for a further 2 h. Cesium carbonate (7.90 g) was added and heated at 100° C. for 20 h. The mixture was cooled to ambient temperature, quenched with water (500 mL), extracted with ethyl acetate (2×200 mL), washed with water (3×300 mL) and brine, dried over anhydrous sodium sulfate, filtered and evaporated under vacuum. The solid residue was treated with ether, filtered and dried to afford the subtitled compound as a beige solid (5.7 g). 1H NMR (400 MHz, DMSO-d6) δ 10.33 (s, 1H), 7.55 (m, 2H), 7.39 (m, 2H), 7.34 (d, J=8.8 Hz, 1H), 7.33 (m, 1H), 6.89 (d, J=9.2 Hz, 1H), 5.27 (s, 2H), 4.67 (s, 2H), 3.32 (s, 3H). The mixture was cooled to ambient temperature quenched with water (500 mL) extracted with ethyl acetate (2×200 mL) washed with water (3×300 mL) and brine dried over anhydrous sodium sulfate filtered evaporated under vacuum The solid residue was treated with ether filtered dried

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

Procedure: Zinc dust (5.5 g) was added portionwise to a suspension of 1-(4-(benzyloxy)-2-hydroxy-3-nitrophenyl)ethanone (5.5 g) in acetic acid (55 mL) over 15 min, whilst maintaining the internal temperature below 40° C. with an ice bath. The mixture was allowed to attain ambient temperature and stirred for a further 2 h. The mixture was filtered through Celite (caution gets hot, do not allow to dry), washed with acetic acid, and the filtrate poured onto ice/water (500 mL). The resulting precipitate was filtered off, washed with water, and dried under vacuum at 40° C. to afford the subtitled compound as a light brown solid (4.8 g). 1H NMR (300 MHz, DMSO-d6) δ 7.53 (m, 2H), 7.48-7.33 (m, 3H), 7.28 (d, J=9.0 Hz, 1H), 6.72 (d, J=9.0 Hz, 1H), 5.29 (s, 2H), 2.59 (s, 3H). whilst maintaining the internal temperature below 40° C. with an ice bath to attain ambient temperature The mixture was filtered through Celite (caution to dry), washed with acetic acid the filtrate poured onto ice/water (500 mL) The resulting precipitate was filtered off washed with water dried under vacuum at 40° C.

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

Procedure: Zinc dust (5.5 g) was added portionwise to a suspension of 1-(4-(benzyloxy)-2-hydroxy-3-nitrophenyl)ethanone (5.5 g) in acetic acid (55 mL) over 15 min, whilst maintaining the internal temperature below 40° C. with an ice bath. The mixture was allowed to attain ambient temperature and stirred for a further 2 h. The mixture was filtered through Celite (caution gets hot, do not allow to dry), washed with acetic acid, and the filtrate poured onto ice/water (500 mL). The resulting precipitate was filtered off, washed with water, and dried under vacuum at 40° C. to afford the subtitled compound as a light brown solid (4.8 g). 1H NMR (300 MHz, DMSO-d6) δ 7.53 (m, 2H), 7.48-7.33 (m, 3H), 7.28 (d, J=9.0 Hz, 1H), 6.72 (d, J=9.0 Hz, 1H), 5.29 (s, 2H), 2.59 (s, 3H). whilst maintaining the internal temperature below 40° C. with an ice bath to attain ambient temperature The mixture was filtered through Celite (caution to dry), washed with acetic acid the filtrate poured onto ice/water (500 mL) The resulting precipitate was filtered off washed with water dried under vacuum at 40° C.

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

Procedure: 2-Chloroacetyl chloride (1.8 mL) was added dropwise to a stirred mixture of 1-(3-amino-4-(benzyloxy)-2-hydroxyphenyl)ethanone (example 11, step c) (5.2 g) and sodium hydrogen carbonate (3.74 g) in DMF (30 mL) and then stirred for 2 h. Cesium carbonate (7.90 g) was added and the mixture heated at 100° C. for 20 h. The mixture was cooled to ambient temperature, quenched with water (500 mL), extracted with ethyl acetate (2×200 mL), washed with water (3×300 mL) and brine, dried over anhydrous sodium sulphate, filtered and evaporated under vacuum. The solid residue was treated with diethyl ether, filtered and dried to afford the subtitled compound as a beige solid. Yield 5.7 g. The mixture was cooled to ambient temperature quenched with water (500 mL) extracted with ethyl acetate (2×200 mL) washed with water (3×300 mL) and brine dried over anhydrous sodium sulphate filtered evaporated under vacuum The solid residue was treated with diethyl ether filtered dried

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

Procedure: Zinc dust (5.5 g) was added portionwise to a suspension of 1-(4-(benzyloxy)-2-hydroxy-3-nitrophenyl)ethanone (example 11, step b) (5.5 g) in acetic acid (55 mL) over 15 minutes, whilst maintaining the internal temperature below 40° C. with an ice bath. The mixture was allowed to attain ambient temperature and stirred for 2 h. The mixture was filtered through Celite (Caution: Gets hot—do not allow to dry), washed with acetic acid, and the filtrate poured onto ice/water (500 mL). The resulting precipitate was filtered off, washed with water, and dried under vacuum at 40° C. to afford the subtitled compound as a light brown solid. Yield 4.8 g. whilst maintaining the internal temperature below 40° C. with an ice bath to attain ambient temperature The mixture was filtered through Celite (Caution to dry), washed with acetic acid the filtrate poured onto ice/water (500 mL) The resulting precipitate was filtered off washed with water dried under vacuum at 40° C.

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

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

Procedure: 2-Chloroacetyl chloride (1.8 mL) was added dropwise to a stirred mixture of 1-(3-amino-4-(benzyloxy)-2-hydroxyphenyl)ethanone (example 11, step c) (5.2 g) and sodium hydrogen carbonate (3.74 g) in DMF (30 mL) and then stirred for 2 h. Cesium carbonate (7.90 g) was added and the mixture heated at 100° C. for 20 h. The mixture was cooled to ambient temperature, quenched with water (500 mL), extracted with ethyl acetate (2×200 mL), washed with water (3×300 mL) and brine, dried over anhydrous sodium sulphate, filtered and evaporated under vacuum. The solid residue was treated with diethyl ether, filtered and dried to afford the subtitled compound as a beige solid. Yield 5.7 g. The mixture was cooled to ambient temperature quenched with water (500 mL) extracted with ethyl acetate (2×200 mL) washed with water (3×300 mL) and brine dried over anhydrous sodium sulphate filtered evaporated under vacuum The solid residue was treated with diethyl ether filtered dried

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

Procedure: Zinc dust (5.5 g) was added portionwise to a suspension of 1-(4-(benzyloxy)-2-hydroxy-3-nitrophenyl)ethanone (example 11, step b) (5.5 g) in acetic acid (55 mL) over 15 minutes, whilst maintaining the internal temperature below 40° C. with an ice bath. The mixture was allowed to attain ambient temperature and stirred for 2 h. The mixture was filtered through Celite (Caution: Gets hot—do not allow to dry), washed with acetic acid, and the filtrate poured onto ice/water (500 mL). The resulting precipitate was filtered off, washed with water, and dried under vacuum at 40° C. to afford the subtitled compound as a light brown solid. Yield 4.8 g. whilst maintaining the internal temperature below 40° C. with an ice bath to attain ambient temperature The mixture was filtered through Celite (Caution to dry), washed with acetic acid the filtrate poured onto ice/water (500 mL) The resulting precipitate was filtered off washed with water dried under vacuum at 40° C.

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

Procedure: 28 g (0.15 mol) 2-bromo-2-methyl-propionyl chloride are added dropwise to 25.7 g (0.10 mol) 1-(3-amino-4-benzyloxy-2-hydroxy-phenyl)-ethanone and 41 g (0.30 mol) potassium carbonate in 215 mL acetonitrile. After 8 hours stirring at reflux temperature the solid is filtered off, the filtrate is evaporated down and the residue is crystallised from ethanol. Yield: 11.2 g (35%); melting range=124-126° C. at reflux temperature the solid is filtered off the filtrate is evaporated down the residue is crystallised from ethanol