methyl 2-(azetidin-3-yl)acetate

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

Procedure: To a solution of 3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3,4-thiadiazol-2-yl)-2-ethylbenzaldehyde (D11) (43 mg) and methyl 3-azetidinylacetate (92 mg) in methanol (10.00 mL) stirred at room temperature was added sodium acetate (45.6 mg) and AcOH (0.032 mL). The reaction mixture was stirred at room temperature for 10 min. Then the solvent was removed by evaporation. The residue was dissolved in dichloromethane (DCM) (10 mL), and sodium triacetoxyborohydride (70.7 mg) was added. Stirring continued for 2 h. Water was added to quench the reaction, and DCM was removed by evaporation. The mixture was extracted by EA 3 times. The combined organic solution was washed by brine, dried over anhydrous Na2SO4. The dried solution was filtered and concentrated to give crude methyl 1-{[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3,4-thiadiazol-2-yl)-2-ethylphenyl]methyl}-3-azetidinecarboxylate (D13) (54 mg). MS (ES): C25H28ClN3O3S requires 485. found 486.0 (M+H+). Then the solvent was removed by evaporation The residue was dissolved in dichloromethane (DCM) (10 mL) sodium triacetoxyborohydride (70.7 mg) was added Stirring continued for 2 h Water was added to quench the reaction, and DCM was removed by evaporation The mixture was extracted by EA 3 times The combined organic solution was washed by brine dried over anhydrous Na2SO4 The dried solution was filtered concentrated

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

Procedure: To a solution of 2-ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}benzaldehyde (D6) (52 mg) and methyl 3-azetidinylacetate (109 mg) in methanol (10.00 mL) stirred at room temperature was added sodium acetate (55 mg) and AcOH (0.035 mL). The reaction mixture was stirred at room temperature for 10 min. After that, the solvent was removed by evaporation. The residue was dissolved in dichloromethane (DCM) (10 mL), sodium triacetoxyborohydride (79 mg) was added. Stirring continued for 2 h. Water was added to quench the reaction, and DCM was removed by evaporation. The mixture was extracted by EA for 3 times. The combined organic solution was washed by brine, dried over anhydrous Na2SO4. The dried solution was filtered and concentrated to afford methyl 1-[(2-ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}phenyl)methyl]-3-azetidinecarboxylate (D8) (64.3 mg), which was used for the next without further purification. MS (ES): C26H28F3N3O3S requires 519. found 520.2 (M+H+). After that, the solvent was removed by evaporation The residue was dissolved in dichloromethane (DCM) (10 mL) sodium triacetoxyborohydride (79 mg) was added Stirring continued for 2 h Water was added to quench the reaction, and DCM was removed by evaporation The mixture was extracted by EA for 3 times The combined organic solution was washed by brine dried over anhydrous Na2SO4 The dried solution was filtered concentrated