1-propan-2-ylazetidin-3-ol

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

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 9.5 parts of 6-methoxy-1-naphthol, 5.8 parts of 1-(iso-propyl)-3-azetidinol and 0.3 part of potassium hydroxide was heated under nitrogen gas at 140° C. for 8 hours with agitation. The reaction mixture was treated in the same manner as in Example 1, and when the resulting hydrochloride was recrystallized from iso-propyl alcohol, there was obtained 17.7 parts of 1-(6'-methoxy-1-naphthoxy)-3-(iso-propylamino)-2-propanol hydrochloride melting at 165° - 167° C. The yield was 57.5%. was recrystallized from iso-propyl alcohol

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

Procedure: When 1-(iso-propyl)-3-azetidinol and 2-allyloxyphenol were reacted in the same manner as in Example 6, 1-(2-allyloxyphenoxy)-3-(iso-propylamino)-2-propanol melting at 76°-79° C was obtained. The yield was 48%.

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

Procedure: 1-(iso-propyl)-3-azetidinol and 2,3-dichlorophenol were reacted in the same manner as in Example 6 to yield 1-(2',3'-dichlorophenoxy)-3-(iso-propylamino)-2-propanol melting at 94°-96° C. The yield was 54%.

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

Procedure: 1-(iso-propyl)-3-azetidinol and m-cresol were reacted in the same manner as in Example 7 to yield 1-(3'-methyl-phenoxy)-3-(iso-propylamino)-2-propanol melting at 80°-82° C. The yield was 81%.

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 5.8 parts of 1-(iso-propyl)-3-azetidinol and 9.3 parts of 1-phenoxyphenol 0.1 part of sodium hydroxide was added, and the mixture was heated under nitrogen gas at 160° C. for 18 hours. The reaction mixture was cooled and extracted with ether. The extract was washed in water and then the solvent was distilled off. Recrystallization of the residue gave 16.1 parts of 1-(p-phenoxyphenoxy)-3-(iso-propylamino)-2-propanol having a melting point of 72°-74° C. The yield was 58%. was added The reaction mixture was cooled extracted with ether The extract was washed in water the solvent was distilled off Recrystallization of the residue

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

Procedure: 1-(isopropyl)-3-azetidinol and α-naphthol were reacted in the same manner as in Example 6 to form 1-(α-naphthoxy)-3-(iso-propylamino)-2-propanol. Then the propanol was dissolved in anhydrous ether and was converted to a hydrochloride by blowing a hydrochloric acid gas into the resulting solution. As a result 1-(α-naphthoxy)-3-(isopropylamino)-2-propanol hydrochloride melting at 162°-164° C was obtained.

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 11.5 parts of 1-(iso-propyl)-3-azetidinol and 15.8 parts of α-naphthol 0.2 part of 182°- potassium hydroxide was added, and the mixture was heated under nitrogen gas at 160° C. for 20 hours. The reaction mixture was cooled and then extracted with ether. The ether extract was washed with 2N-NaOH aqueous solution and then with water. The liquor was dried over anhydrous sodium sulfate and the solvent was distilled off. The residue was recrystallized for cyclohexane or subjected to distillation under reduced pressure. As a result 19.6 parts of 1-(α-naphthoxy)-3-(isopropylamino)-2-propanol having a melting point of 94°-96° C. and a boiling point of 158°-159° C. under 2.5 mm Hg were obtained. The yield was 76%. The residue of infra-red spectrum analysis of the product are as follows: was added The reaction mixture was cooled extracted with ether The ether extract was washed with 2N-NaOH aqueous solution The liquor was dried over anhydrous sodium sulfate the solvent was distilled off The residue was recrystallized for cyclohexane subjected to distillation under reduced pressure

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

Procedure: The hydrochloride salt of 1-isopropyl-3-azetidinol (168 g; 1 mole) was partitioned between dilute sodium hydroxide and 700 ml of benzene. The benzene solution was dried over anhydrous sodium sulfate and concentrated to one half volume. The volume was made back to 700 ml with dry benzene and 110 g (1.1 mole) of triethylamine added. To this was added dropwise 115 g (1 mole) of methanesulfonyl chloride while cooling with an ice bath. The mixture was stirred at room temperature for one hour and filtered. The filter cake was washed twice with 100 ml of benzene and all the benzene filtrates combined. The benzene filtrate was extracted with 300 ml of 4N hydrochloric acid followed by 100 ml of water. The aqueous extracts were combined and the pH adjusted to 7 with sodium hydroxide. The solution was treated with 65 g (1 mole) of sodium azide and heated to reflux for 20 hr and cooled to room temperature with an ice bath. A solution (673 ml) of 23% aqueous ammonium sulfide was added while cooling with an ice bath to 30° C. and the solution was stirred at room temperature for 6 hr. The solution was continuously extracted with chloroform for 35 hr. (The condenser became plugged overnight and the pressure caused a joint to open and an unknown amount of material was lost). The chloroform was concentrated and distilled. Yield 18.5 g, b.p. 70°-80° C./20-30 mm. Two grams of the distillate was dissolved in ethanol and treated with ethereal hydrogen chloride. The resulting crystals were recrystallized from ethanol, yield of title compound from the 2 g sample was 1.35 g, m.p. 167°-170° C. The benzene solution was dried over anhydrous sodium sulfate concentrated to one half volume added while cooling with an ice bath filtered The filter cake was washed twice with 100 ml of benzene and all the benzene filtrates The benzene filtrate was extracted with 300 ml of 4N hydrochloric acid heated to reflux for 20 hr cooled to room temperature with an ice bath while cooling with an ice bath to 30° C. the solution was stirred at room temperature for 6 hr The solution was continuously extracted with chloroform for 35 hr (The condenser became plugged overnight The chloroform was concentrated distilled Two grams of the distillate was dissolved in ethanol treated with ethereal hydrogen chloride The resulting crystals were recrystallized from ethanol, yield of title compound from the 2 g sample

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

Procedure: The hydrochloride salt of 1-isopropyl-3-azetidinol (168 g; 1 mole) was partitioned between dilute sodium hydroxide and 700 ml of benzene. The benzene solution was dried over anhydrous sodium sulfate and concentrated to one half volume. The volume was made back to 700 ml with dry benzene and 110 g (1.1 mole) of triethylamine added. To this was added dropwise 115 g (1 mole) of methanesulfonyl chloride while cooling with an ice bath. The mixture was stirred at room temperature for one hour and filtered. The filter cake was washed twice with 100 ml of benzene and all the benzene filtrates combined. The benzene filtrate was extracted with 300 ml of 4N hydrochloric acid followed by 100 ml of water. The aqueous extracts were combined and the pH adjusted to 7 with sodium hydroxide. The solution was treated with 65 g (1 mole) of sodium azide and heated to reflux for 20 hr and cooled to room temperature with an ice bath. A solution (673 ml) of 23% aqueous ammonium sulfide was added while cooling with an ice bath to 30° C. and the solution was stirred at room temperature for 6 hr. The solution was continuously extracted with chloroform for 35 hr. (The condenser became plugged overnight and the pressure caused a joint to open and an unknown amount of material was lost). The chloroform was concentrated and distilled. Yield 18.5 g, b.p. 70°-80° C./20-30 mm. Two grams of the distillate was dissolved in ethanol and treated with ethereal hydrogen chloride. The resulting crystals were recrystallized from ethanol, yield of title compound from the 2 g sample was 1.35 g, m.p. 167°-170° C. The benzene solution was dried over anhydrous sodium sulfate concentrated to one half volume added while cooling with an ice bath filtered The filter cake was washed twice with 100 ml of benzene and all the benzene filtrates The benzene filtrate was extracted with 300 ml of 4N hydrochloric acid heated to reflux for 20 hr cooled to room temperature with an ice bath while cooling with an ice bath to 30° C. the solution was stirred at room temperature for 6 hr The solution was continuously extracted with chloroform for 35 hr (The condenser became plugged overnight The chloroform was concentrated distilled Two grams of the distillate was dissolved in ethanol treated with ethereal hydrogen chloride The resulting crystals were recrystallized from ethanol, yield of title compound from the 2 g sample

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 6.1 g of 6-methyl-3-pyridinol, 5.5 g of 1-isopropyl-3-azetidinol, 0.3 g of potassium hydroxide and 25 ml of benzyl alcohol is stirred for 16 hours under nitrogen in a bath at 150° C. After cooling, the reaction mixture is diluted with 50 ml of ether and extracted with 30 ml of 4 N hydrochloric acid. The aqueous phase is separated off, rendered alkaline with concentrated sodium hydroxide solution and extracted with 100 ml of methylene chloride. 3-(3'-Isopropylamino-2'-hydroxy-propoxy)-6-methyl-pyridine is isolated from the crude product thus obtained by bulb tube distillation at 130°-140° C. bath temperature and 0.04 mm Hg. It is identical in its properties with the product obtained in Example 19. After cooling extracted with 30 ml of 4 N hydrochloric acid The aqueous phase is separated off extracted with 100 ml of methylene chloride

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 6.1 g of 6-methyl-3-pyridinol, 5.5 g of 1-isopropyl-3-azetidinol, 0.3 g of potassium hydroxide and 25 ml of benzyl alcohol is stirred for 16 hours under nitrogen in a bath at 150° C. After cooling, the reaction mixture is diluted with 50 ml of ether and extracted with 30 ml of 4 N hydrochloric acid. The aqueous phase is separated off, rendered alkaline with concentrated sodium hydroxide solution and extracted with 100 ml of methylene chloride. 3-(3'-Isopropylamino-2'-hydroxy-propoxy)-6-methyl-pyridine is isolated from the crude product thus obtained by bulb tube distillation at 130°-140° C. bath temperature and 0.04 mm Hg. It is identical in its properties with the product obtained in Example 19. After cooling extracted with 30 ml of 4 N hydrochloric acid The aqueous phase is separated off extracted with 100 ml of methylene chloride