2-(4-hydroxyphenyl)acetamide

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

Procedure: (0.0032 g, 0.007 mmol) of the platinum complex, prepared as in Example 1, was stirred with 4-hydroxybenzyl cyanide (1.0 g, 7.5 mmol) and 5 ml (0.28 mol) of water and 5 ml ethanol and the mixture heated under reflux for 18 hours. After cooling the liquids were removed using a rotary evaporator to give 4-hydroxy phenylacetamide (1.116 g) corresponding to 98% yield. (0.0032 g, 0.007 mmol) of the platinum complex, prepared as in Example 1 the mixture heated under reflux for 18 hours After cooling the liquids were removed a rotary evaporator

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

Procedure: A mixture of p-hydroxyphenylacetamide (3.8 g), ethyl 4-bromobutyrate (3.6 ml) and K2CO3 (3.45 g) was stirred for 12 hr in DMF (30 ml). The mixture was diluted with water (100 ml); the solid was filtered and air dried. Crystallization of the solid from ethanol gave 4 g (60%) of the title compound as white crystals; mp 144.5°-145.5°. the solid was filtered air dried Crystallization of the solid from ethanol

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

Procedure: Methyl 4-Hydroxyphenylacetate (4) (0.83 g) was dissolved in saturated methanolic ammonia (30 ml) and placed in a thick walled tube with Teflon screw cap. The solution was stirred in this sealed tube at room temperature for 72 hours. Reaction mixture was concentrated and redissolved in methanol-chloroform (2:8 volume by volume, 75 ml). No crystallization occurred so the solution was concentrated to half its volume and hexane was added with heating. Cooling to 0° C. gave crystals of 4-Hydroxyphenylacetamide (13) (0.524 g). This was confirmed by spectroscopy--1H NMR (d6DMSO+CF3CO2D) δ 3.23 (s, 2 H), 6.63 (d, 2 H), 7.00 (d, 2 H). screw cap Reaction mixture was concentrated redissolved in methanol-chloroform (2:8 volume by volume, 75 ml) No crystallization was concentrated to half its volume and hexane was added with heating Cooling to 0° C.

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

Procedure: P-Hydroxyphenylacetamide (1 g) and (S)-glycidyl p-toluenesulfonate (1.51 g, 99.3% e.e.) were dissolved in acetone (30 ml). Potassium carbonate (1.19 g) was added to the solution and stirred for 30 hours under refluxing. After the reaction, inorganic materials were filtered off and acetone was removed to give 1.43 g of crude (S)-1-[p-(carbamoylmethyl)phenoxy-2,3-epoxypropane. Then, crude (S)-1-[p-(carbamoylmethyl)phenoxy-2,3-epoxypropane (1.43 g) was dissolved in methanol (8 ml). The solution was dropped in isopropylamine (6.8 g) under cooling to 10° C. over a period of 1 hour and the reaction temperature was raised to room temperature and stirred for 7 hours. After the reaction, the mixture was condensed in vacuo until crystals beginning to separate, cooled, filtrated by suction and dried in vacuo to give crude (S)-atenolol (1.29 g). The optical purity of it was 62.8% e.e. by measurement of Chiral column OD (Daisel Chemical industries Ltd.). under refluxing After the reaction, inorganic materials were filtered off acetone was removed

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: p-Hydroxyphenylacetamide (30.02 g) was dissolved in 106.5 g of water containing sodium hydroxide (9.6 g) and the solution was cooled to 5° C. Epichlorohydrin (18.5 g, 98.9% e.e.) was dropped in the solution over a period of 10 minutes and the mixture was stirred for 24 hours at the same temperature. After confirmation of the progress of the reaction being 98% by HPLC, the reaction mixture was neutralized with 0.1 N hydrochloric acid at the same temperature and then dropped in isopropylamine (240 g) under cooling to 10° C. over a period of 1 hour and the reaction temperature was raised to room temperature and stirred for 3.5 hours. After the reaction, the reaction mixture was condensed in vacuo until crystals beginning to separate, cooled and filtrated by suction and dried in vacuo to give crude (S)-atenolol (51.26 g). The optical purity of it was 91.2% e.e. by measurement of Chiral column OD (Daisel Chemical Industries Ltd.). under cooling to 10° C. over a period of 1 hour the reaction temperature was raised to room temperature stirred for 3.5 hours After the reaction condensed in vacuo until crystals to separate cooled filtrated by suction dried in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: p-Hydroxyphenylacetamide (1 g) was dissolved in DMF (5 ml) under nitrogen atmosphere and the solution was cooled to 0° C. Cesium fluoride (3.02 g) and sodium iodide (0.1 g) were added thereto and the mixture was stirred for 1 hour. Then (R)-epichlorohydrin (0.62 g, 98.4% e.e.) was added thereto and the mixture was stirred for 30 hours at the same temperature. After the reaction, the reaction mixture was dropped over a period of one hour in isopropylamine (9 g) previously cooled to 10° C. The temperature of the solution was raised to room temperature and stirred for 12 hours. Then the product was treated in the same manner as Example 1 to give 1.53 g of (S)-atenolol (yield 87%, optical purity 98.3% e.e.) as colorless crystals. the mixture was stirred for 30 hours at the same temperature After the reaction previously cooled to 10° C The temperature of the solution was raised to room temperature stirred for 12 hours Then the product was treated in the same manner as Example 1

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 190 ml of 80% strength sulfuric acid solution are added to a mixture of 16 g of mandelic acid and 15 g of 4-hydroxyphenylacetamide [J. Am. Chem. Soc. (1946) p. 2633]. The medium is heated very rapidly to 80° C. and immediately hydrolyzed using 600 g of ice. The aqueous phase is extracted with 3 times 200 ml of chloroform and the organic phase washed with saturated sodium bicarbonate solution, dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product obtained is recrystallized in chloroform. The aqueous phase is extracted with 3 times 200 ml of chloroform the organic phase washed with saturated sodium bicarbonate solution dried over anhydrous sodium sulfate concentrated under vacuum

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

Procedure: (0.0032 g, 0.007 mmol) of the platinum complex, prepared as in Example 1, was stirred with 4-hydroxybenzyl cyanide (1.0 g, 7.5 mmol) and 5 ml (0.28 mol) of water and 5 ml ethanol and the mixture heated under reflux for 18 hours. After cooling the liquids were removed using a rotary evaporator to give 4-hydroxy phenylacetamide (1.116 g) corresponding to 98% yield. (0.0032 g, 0.007 mmol) of the platinum complex, prepared as in Example 1 the mixture heated under reflux for 18 hours After cooling the liquids were removed a rotary evaporator

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

Procedure: (0.0032 g, 0.007 mmol) of the platinum complex, prepared as in Example 1, was stirred with 4-hydroxybenzyl cyanide (1.0 g, 7.5 mmol) and 5 ml (0.28 mol) of water and 5 ml ethanol and the mixture heated under reflux for 18 hours. After cooling the liquids were removed using a rotary evaporator to give 4-hydroxy phenylacetamide (1.116 g) corresponding to 98% yield. (0.0032 g, 0.007 mmol) of the platinum complex, prepared as in Example 1 the mixture heated under reflux for 18 hours After cooling the liquids were removed a rotary evaporator

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

Procedure: A mixture of p-hydroxyphenylacetamide (3.8 g), ethyl 4-bromobutyrate (3.6 ml) and K2CO3 (3.45 g) was stirred for 12 hr in DMF (30 ml). The mixture was diluted with water (100 ml); the solid was filtered and air dried. Crystallization of the solid from ethanol gave 4 g (60%) of the title compound as white crystals; mp 144.5°-145.5°. the solid was filtered air dried Crystallization of the solid from ethanol

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

Procedure: Methyl 4-Hydroxyphenylacetate (4) (0.83 g) was dissolved in saturated methanolic ammonia (30 ml) and placed in a thick walled tube with Teflon screw cap. The solution was stirred in this sealed tube at room temperature for 72 hours. Reaction mixture was concentrated and redissolved in methanol-chloroform (2:8 volume by volume, 75 ml). No crystallization occurred so the solution was concentrated to half its volume and hexane was added with heating. Cooling to 0° C. gave crystals of 4-Hydroxyphenylacetamide (13) (0.524 g). This was confirmed by spectroscopy--1H NMR (d6DMSO+CF3CO2D) δ 3.23 (s, 2 H), 6.63 (d, 2 H), 7.00 (d, 2 H). screw cap Reaction mixture was concentrated redissolved in methanol-chloroform (2:8 volume by volume, 75 ml) No crystallization was concentrated to half its volume and hexane was added with heating Cooling to 0° C.

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

Procedure: A mixture of p-hydroxyphenylacetamide (3.8 g), ethyl 4-bromobutyrate (3.6 ml) and K2CO3 (3.45 g) was stirred for 12 hr in DMF (30 ml). The mixture was diluted with water (100 ml); the solid was filtered and air dried. Crystallization of the solid from ethanol gave 4 g (60%) of the title compound as white crystals; mp 144.5°-145.5°. the solid was filtered air dried Crystallization of the solid from ethanol