3-氟甲基氮杂环丁烷-1-羧酸叔丁酯

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: tert-Butyl 3-(fluoromethyl)azetidine-1-carboxylate (0.1 g, 0.53 mmol) and trifluoroacetic acid/DCM (1:1, 5.3 mL) was stir at room temperature for 30 min. Then the reaction mixture was concentrated on a rotary evaporator to afford 3-(fluoromethyl)azetidine 2,2,2-trifluoroacetate as clear oil. 1H NMR (DMSO-d6; TFA salt): δ 8.74 (br, 2H), 4.54 (dd, 2H), 4.08-3.98 (m, 2H), 3.84-3.76 (m, 2H), 3.20-3.06 (m, 1H). Then the reaction mixture was concentrated on a rotary evaporator

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: tert-Butyl 3-(fluoromethyl)azetidine-1-carboxylate (0.1 g, 0.53 mmol) and trifluoroacetic acid/DCM (1:1, 5.3 mL) was stir at room temperature for 30 min. Then the reaction mixture was concentrated on a rotary evaporator to afford 3-(fluoromethyl)azetidine 2,2,2-trifluoroacetate as clear oil. 1H NMR (DMSO-d6; TFA salt): δ 8.74 (br, 2H), 4.54 (dd, 2H), 4.08-3.98 (m, 2H), 3.84-3.76 (m, 2H), 3.20-3.06 (m, 1H). Then the reaction mixture was concentrated on a rotary evaporator

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of tert-butyl 3-(((methylsulfonyl)oxy)methyl)azetidine-1-carboxylate (12.5 g, 47 mmol) and 235 mL tetrabutylammonium fluoride (1M solution in THF, 5 equiv.) was heated at reflux for 18 h. The reaction mixture was cooled to room temperature and excess THF was removed on a rotary evaporator. The residue was dissolved in ethyl acetate. The organic phase was washed with sat'd aqueous NaHCO3, washed with water, washed with brine, dried over Na2SO4, filtered and concentrated on a rotary evaporator to give the crude product. This crude product was purified by silica gel chromatography to afford tert-butyl 3-(fluoromethyl)azetidine-1-carboxylate as clear oil (7.5 g). 1H NMR (DMSO-d6): δ 4.52 (dd, 2H), 3.89 (br, 2H), 3.61 (br, 2H), 2.92-2.77 (m, 1H), 1.36 (s, 9H). was heated at reflux for 18 h excess THF was removed on a rotary evaporator The residue was dissolved in ethyl acetate The organic phase was washed with sat'd aqueous NaHCO3 washed with water washed with brine dried over Na2SO4 filtered concentrated on a rotary evaporator to give the crude product This crude product was purified by silica gel chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: tert-Butyl 3-(fluoromethyl)azetidine-1-carboxylate (0.1 g, 0.53 mmol) and trifluoroacetic acid/DCM (1:1, 5.3 mL) was stir at room temperature for 30 min. Then the reaction mixture was concentrated on a rotary evaporator to afford 3-(fluoromethyl)azetidine 2,2,2-trifluoroacetate as clear oil. 1H NMR (DMSO-d6; TFA salt): δ 8.74 (br, 2H), 4.54 (dd, 2H), 4.08-3.98 (m, 2H), 3.84-3.76 (m, 2H), 3.20-3.06 (m, 1H). Then the reaction mixture was concentrated on a rotary evaporator

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of tert-butyl 3-(((methylsulfonyl)oxy)methyl)azetidine-1-carboxylate (12.5 g, 47 mmol) and 235 mL tetrabutylammonium fluoride (1M solution in THF, 5 equiv.) was heated at reflux for 18 h. The reaction mixture was cooled to room temperature and excess THF was removed on a rotary evaporator. The residue was dissolved in ethyl acetate. The organic phase was washed with sat'd aqueous NaHCO3, washed with water, washed with brine, dried over Na2SO4, filtered and concentrated on a rotary evaporator to give the crude product. This crude product was purified by silica gel chromatography to afford tert-butyl 3-(fluoromethyl)azetidine-1-carboxylate as clear oil (7.5 g). 1H NMR (DMSO-d6): δ 4.52 (dd, 2H), 3.89 (br, 2H), 3.61 (br, 2H), 2.92-2.77 (m, 1H), 1.36 (s, 9H). was heated at reflux for 18 h excess THF was removed on a rotary evaporator The residue was dissolved in ethyl acetate The organic phase was washed with sat'd aqueous NaHCO3 washed with water washed with brine dried over Na2SO4 filtered concentrated on a rotary evaporator to give the crude product This crude product was purified by silica gel chromatography