4-[(2S)-2-hydroxy-3-(propan-2-ylamino)propoxy]phenol

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

Procedure: To a mixture of the dihydrochloride salt of 1-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]-4-(2-chloroethyl)piperazine (12.4 g) and (S)-1-(4-hydroxyphenoxy)-3-(1-methylethyl)amino-2-propanol (6.2 g) in 100 ml dimethylsulfoxide was added 15.25 ml of 5N sodium hydroxide solution and the mixture was stirred under argon for 2 hours at 50°. The reaction was worked up as in method A to give 14.7 g of the crude (S)-1-(1-methylethylamino)-3-[4-[2-[4-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]piperazin-1-yl]ethoxy]phenoxy]-2-propanol.

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

Procedure: To a solution of the chloride of 1-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]-4-(2-chloroethyl)piperazine (9.4 g) in 75 ml dimethylsulfoxide was added (S)-1-(4-hydroxyphenoxy)-3-(1-methylethyl)amino-2-propanol (6.0 g) followed by 6.25 ml 4N sodium hydroxide solution. The mixture was stirred under argon at 55° for 2 hours then was cooled and diluted with 500 ml water and 35 ml 1N sodium hydroxide, and extracted with dichloromethane (3×). The extracts were backwashed with water (2×), dried over potassium carbonate and the solvent was removed in vacuo to give 12.8 g of crude (S)-1-(1-methylethylamino)-3-[4-[2-[4-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]piperazin-1-yl]ethoxy]phenoxy]-2-propanol as an oil. then was cooled extracted with dichloromethane (3×) dried over potassium carbonate the solvent was removed in vacuo

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

Procedure: A solution of (S)-1-(4-benzyloxyphenoxy)-3-(1-methylethyl)amino-2-propanol (53.4 g) in 500 ml methanol was hydrogenated over 5 g 10% palladium on carbon (room temperature; 1 atmosphere). Within 40 minutes the uptake of nitrogen stopped abruptly after the absorption of 4,300 ml. The mixture was filtered through Celite and the filtrate was concentrated to dryness under reduced pressure. The resulting colorless solid residue was crystallized from acetone to give 35.2 g of (S)-1-(4-hydroxyphenoxy)-3-(1-methylethyl)amino-2-propanol, mp 127°-129°; [α]D25 -20.67° (c, 1.0, 0.1N hydrochloric acid). after the absorption of 4,300 ml The mixture was filtered through Celite the filtrate was concentrated to dryness under reduced pressure The resulting colorless solid residue was crystallized from acetone

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

Procedure: A solution of (S)-1-(4-benzyloxyphenoxy)-3-(1-methylethyl)amino-2-propanol (53.4 g) in 500 ml methanol was hydrogenated over 5 g 10% palladium on carbon (room temperature; 1 atmosphere). Within 40 minutes the uptake of nitrogen stopped abruptly after the absorption of 4,300 ml. The mixture was filtered through Celite and the filtrate was concentrated to dryness under reduced pressure. The resulting colorless solid residue was crystallized from acetone to give 35.2 g of (S)-1-(4-hydroxyphenoxy)-3-(1-methylethyl)amino-2-propanol, mp 127°-129°; [α]D25 -20.67° (c, 1.0, 0.1N hydrochloric acid). after the absorption of 4,300 ml The mixture was filtered through Celite the filtrate was concentrated to dryness under reduced pressure The resulting colorless solid residue was crystallized from acetone