1-tert-butylazetidin-3-ol

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

Conditions: temp:70.01; pressure:0.00; stir:

Procedure: Dilution of the aliquot (2 uL) with DMSO (200 uL).

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

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

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

Procedure: To a solution of 1-tert-butylazetidin-3-ol (24 mg, 0.19 mmol) and 7-chloro-3-(4-chlorophenyl)-2-(2-chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidine (I-3A-4b; 36 mg, 0.093 mmol) in THF (1 ml) was added NaH (60% dispersion in oil, 9.3 mg, 0.23 mmol). After stirring for 1 hour, the reaction was quenched with water, extracted from saturated aqueous NaHCO3 with ethyl acetate, the combined organic layers were dried (MgSO4), concentrated and purified on a Biotage™ Flash 12M column using 0–5% methanol in methylene chloride as eluant to afford 9A-1 (26 mg, 59%) as a colorless solid: +ESI MS (M+1) 481.4; 1H NMR (400 MHz, CD2Cl2) δ 7.50–7.36 (m, 6H), 7.24 (d, J=8.7 Hz, 2H), 5.99 (s, 1H), 5.10–5.02 (m, 1H), 3.76–3.70 (br m, 2H), 3.49–3.43 (br m, 2H), 2.60 (s, 3H), 1.00 (s, 9H). the reaction was quenched with water extracted from saturated aqueous NaHCO3 with ethyl acetate the combined organic layers were dried (MgSO4) concentrated purified on a Biotage™ Flash 12M column to afford 9A-1 (26 mg, 59%) as a colorless solid

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

Procedure: A mixture of 21.8 parts of m-aminophenol, 22 parts of 1-(tert.-butyl)-3-azetidinol and 0.7 part of potassium hydroxide was heated under nitrogen gas at 140° C. for 8 hours with agitation. The reaction mixture was cooled and treated in the same manner as in Example 39. Recrystallization from benzene gave 17.2 parts of 1-(3'-aminophenoxy)-3-(tert.-butylamino)-2-propanol in the form of colorless needles melting at 105° - 106° C. The yield was 42.3%. The results of infra-red spectrum analysis are as follows: The reaction mixture was cooled treated in the same manner as in Example 39 Recrystallization from benzene

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

Procedure: A mixture of 9.1 parts of 2,3-dimethyl-4-methoxyphenol, 6.5 parts of 1-(tert.-butyl)-3-azetidinol and 0.3 part of potassium hydroxide was heated under nitrogen gas at 140° C. for 8 hours with agitation. The reaction product was dissolved in 100 parts of 2N-hydrochloric acid aqueous solution and washed twice with 100 parts of ether. The water layer was made alkaline with 4N-sodium hydroxide aqueous solution, and the resulting crystals were recovered by filtration and dried. Then the crystals were dissolved in 100 parts of ether and decolored. The decolored liquid was concentrated and allowed to cool. As a result 10.2 parts of 1-(2',3'-dimethyl-4'-methoxyphenoxy)-3-(tert.-butylamino)-2-propanol melting at 73° - 75° C were obtained. The yield was 72.5%. The results of infra-red spectrum analysis and nuclear magnetic resonance analysis of the product are as follows: washed twice with 100 parts of ether the resulting crystals were recovered by filtration dried Then the crystals were dissolved in 100 parts of ether The decolored liquid was concentrated to cool

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

Procedure: A mixture of 11 parts of hydroquinone, 6.5 parts of 1-(tert.-butyl)-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 cooled and dissolved into 50 parts of 4N-hydrochloric acid aqueous solution. The resulting solution was washed with 50 parts of chloroform. The water layer was acidified with concentrated hydrochloric acid, evaporated and solidified. The residue was dissolved in isopropyl alcohol and filtered. The filtrate was decolored with active carbon and allowed to cool. As a result 6.9 parts of 1-(p-hydroxyphenoxy)-3-(tert.-butylamino)-2-propanol hydrochloride melting at 201° - 203° C were obtained. The yield was 58%. The results of infra-red spectrum analysis and nuclear magnetic resonance analysis of the resulting hydrochloride are as follows: The reaction mixture was cooled The resulting solution was washed with 50 parts of chloroform evaporated The residue was dissolved in isopropyl alcohol filtered to cool

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

Procedure: A mixture of 21.8 g of p-aminophenol, 22 g of 1-(tert.-butyl)-3-azetidinol and 0.73 g of potassium hydroxide was heated under nitrogen gas at 140° C. for 8 hours with agitation. The reaction mixture was cooled and dissolved in concentrated hydrochloric acid and the solution was extracted with ether. The hydrochloric acid aqueous solution was made alkaline with 10% -NaOH aqueous solution and then extracted with ether. The ether solution was washed with water and dried over anhydrous sodium sulfate. Then ether was distilled off and the residue was recrystallized from benzene. As a result 8g of 1-(p-aminophenoxy)-3-(tert.-butylamino)-2-propanol melting at 125° - 127° C were obtained. The results of infra-red spectrum analysis and nuclear magnetic resonance analysis are as follows: The reaction mixture was cooled the solution was extracted with ether extracted with ether The ether solution was washed with water dried over anhydrous sodium sulfate Then ether was distilled off the residue was recrystallized from benzene

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4.4 parts of 3-benzyloxy-1-(tert.butyl)azetidine in 30 parts of ethanol was taken into an autoclave together with 2 parts of Raney nickel as catalyst. Under a hydrogen gas pressure of 100 atmospheres, the mixture was stirred at 40° C. for 15 hours to perform the reduction. The catalyst was separated by filtration, and the remaining ethanol solution was concentrated to dryness. The resulting oily substance was dissolved in n-hexane and cooled. As a result 2.0 parts of 1-(tert.-butyl)-3-azetidinol melting at 42° - 43° C. The yield was 76%. The results of infra-red spectrum analysis and nuclear magnetic resonance analysis of the product are as follows: The catalyst was separated by filtration the remaining ethanol solution was concentrated to dryness The resulting oily substance was dissolved in n-hexane cooled

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

Procedure: 1-(tert.-butyl)-3-azetidinol and 5,6,7,8-tetrahydro-α-naphthol were reacted in the same manner as in Example 1 to form 1-(5,6,7,8-tetrahydro-α-naphthoxy)-3-(tert.-butylamino)-2-propanol. A hydrochloric acid gas was blown into the obtained propanol. As a result 1-(5,6,7,8-tetrahydro-1-naphthoxy)-3-(tert.-butylamino)-2-propanol hydrochloride having a melting point of 148°-150° C was obtained. The yield was 70%.

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

Procedure: To a mixture of 6.5 parts of 1-(tert.-butyl)-3-azetidinol and 7.9 parts of α-naphthol 0.2 part of potassium hydroxide was added, and the mixture was heated at 160° C. for 24 hours. The reaction mixture was cooled and then dissolved in 100 parts of ether. The solution was washed twice with 50 parts of 2N-sodium hydroxide aqueous solution and extracted three times with 50 parts of 2N-hydrochloric acid aqueous solution. The extract was washed with 50 parts of ether and made alkaline by addition of 2N-sodium hydroxide aqueous solution. Extraction was conducted three times with 50 parts of benzene, and the extract was dried over anhydrous sodium sulfate. Then benzene was distilled off and the residue was solidified by drying under reduced pressure. The solid residue was subjected to distillation under reduced pressure. As a result 5 parts of 1-(α-naphthoxy)-3-(tert.-butylamino)-2-propanol boiling at 175°-180° C. under 1.5 mm Hg were obtained. A part of the product was dissolved in 5 parts of anhydrous ether and the product was converted to a hydrochloride by adding a hydrochloric acid gas to the resulting ether solution. The hydrochloric was recrystallized twice from a mixed solvent of ethyl acetate and ether. As a result 1-(α-naphthoxy)-3-(tert.-butylamino)-2-propanol hydrochloride having a melting point of 182°-184° C was obtained. was added The reaction mixture was cooled The solution was washed twice with 50 parts of 2N-sodium hydroxide aqueous solution extracted three times with 50 parts of 2N-hydrochloric acid aqueous solution The extract was washed with 50 parts of ether by addition of 2N-sodium hydroxide aqueous solution Extraction the extract was dried over anhydrous sodium sulfate Then benzene was distilled off by drying under reduced pressure The solid residue was subjected to distillation under reduced pressure