3-ethoxyoxan-4-one

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: To a solution of (1R,3S)-3-isopropyl-3-({4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}carbonyl)cyclopentanamine dihydrochloride (200 mg, 0.438 mmol), 3-ethoxytetrahydro-4H-pyran-4-one (130 mg, 0.88 mmol) and triethylamine (0.18 mL, 1.3 mmol) in methylene chloride (10 mL) was added sodium triacetoxyborohydride (180 mg, 0.88 mmol). After being stirred at room temperature overnight, the reaction mixture was diluted with EtOAc and washed with saturated Na2CO3. The aqueous layer was extracted with EtOAc three times. The combined organic layers were dried (MgSO4), concentrated and purified on silica gel (EtOAc to 1% Et3N/EtOAc to 5% Et3N/EtOAc) affording 230 mg of product. The product was separated by chiral HPLC to give two major isomers: isomer 1 (110 mg) and isomer 2 (77 mg). MS calculated for C27H40F3N3O3: (M+H) 512; found 512.2. washed with saturated Na2CO3 The aqueous layer was extracted with EtOAc three times The combined organic layers were dried (MgSO4) concentrated purified on silica gel (EtOAc to 1% Et3N/EtOAc to 5% Et3N/EtOAc)

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

实验步骤: To a solution of 3-ethoxy-4,4-dimethoxytetrahydro-2H-pyran (2.1 g, 11 mmol) in THF/water (50 mL/10 mL) was added concentrated HCl (6 mL). After being stirred at room temperature for 1 h, the mixture was diluted with EtOAc. The organic layer was separated and the aqueous layer was extracted with ether five times. The combined organic layers were dried over MgSO4, filtered and concentrated to give 1.55 g (97%) of the desired product 1H NMR (CDCl3) δ 4.30-3.50 (7H, m), 2.62-2.57 (2H, m), 1.30-1.20 (3H, t, J=5 Hz). The organic layer was separated the aqueous layer was extracted with ether five times The combined organic layers were dried over MgSO4 filtered concentrated

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

实验步骤: To a solution of 3-ethoxy-4,4-dimethoxytetrahydro-2H-pyran (2.1 g, 11 mmol) in THF/water (50 mL/10 mL) was added concentrated HCl (6 mL). After being stirred at room temperature for 1 h, the mixture was diluted with EtOAc. The organic layer was separated and the aqueous layer was extracted with ether five times. The combined organic layers were dried over MgSO4, filtered and concentrated to give 1.55 g (97%) of the desired product 1H NMR (CDCl3) δ 4.30-3.50 (7H, m), 2.62-2.57 (2H, m), 1.30-1.20 (3H, t, J=5 Hz). The organic layer was separated the aqueous layer was extracted with ether five times The combined organic layers were dried over MgSO4 filtered concentrated

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

实验步骤: To a solution of (1R,3S)-3-isopropyl-3-({4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}carbonyl)cyclopentanamine dihydrochloride (200 mg, 0.438 mmol), 3-ethoxytetrahydro-4H-pyran-4-one (130 mg, 0.88 mmol) and triethylamine (0.18 mL, 1.3 mmol) in methylene chloride (10 mL) was added sodium triacetoxyborohydride (180 mg, 0.88 mmol). After being stirred at room temperature overnight, the reaction mixture was diluted with EtOAc and washed with saturated Na2CO3. The aqueous layer was extracted with EtOAc three times. The combined organic layers were dried (MgSO4), concentrated and purified on silica gel (EtOAc to 1% Et3N/EtOAc to 5% Et3N/EtOAc) affording 230 mg of product. The product was separated by chiral HPLC to give two major isomers: isomer 1 (110 mg) and isomer 2 (77 mg). MS calculated for C27H40F3N3O3: (M+H) 512; found 512.2. washed with saturated Na2CO3 The aqueous layer was extracted with EtOAc three times The combined organic layers were dried (MgSO4) concentrated purified on silica gel (EtOAc to 1% Et3N/EtOAc to 5% Et3N/EtOAc)

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

实验步骤: To a solution of 3-ethoxy-4,4-dimethoxytetrahydro-2H-pyran (2.1 g, 11 mmol) in THF/water (50 mL/10 mL) was added concentrated HCl (6 mL). After being stirred at room temperature for 1 h, the mixture was diluted with EtOAc. The organic layer was separated and the aqueous layer was extracted with ether five times. The combined organic layers were dried over MgSO4, filtered and concentrated to give 1.55 g (97%) of the desired product. 1H NMR (CDCl3) δ 4.30-3.50 (7H, m), 2.62-2.57 (2H, m), 1.30-1.20 (3H, t, J=5 Hz). The organic layer was separated the aqueous layer was extracted with ether five times The combined organic layers were dried over MgSO4 filtered concentrated

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

实验步骤: To a solution of (1R,3S)-3-isopropyl-3-({4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}carbonyl)cyclopentanamine dihydrochloride (200 mg, 0.438 mmol), 3-ethoxytetrahydro-4H-pyran-4-one (130 mg, 0.88 mmol) and triethylamine (0.18 mL, 1.3 mmol) in methylene chloride (10 mL) was added sodium triacetoxyborohydride (180 mg, 0.88 mmol). After being stirred at room temperature overnight, the reaction mixture was diluted with EtOAc and washed with saturated Na2CO3. The aqueous layer was extracted with EtOAc three times. The combined organic layers were dried (MgSO4), concentrated and purified on silica gel (EtOAc to 1% Et3N/EtOAc to 5% Et3N/EtOAc) affording 230 mg of product. The product was separated by chiral HPLC to give two major isomers: isomer 1 (110 mg) and isomer 2 (77 mg). MS calculated for C27H40F3N3O3: (M+H) 512; found 512.2. washed with saturated Na2CO3 The aqueous layer was extracted with EtOAc three times The combined organic layers were dried (MgSO4) concentrated purified on silica gel (EtOAc to 1% Et3N/EtOAc to 5% Et3N/EtOAc)

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

实验步骤: To a solution of 3-ethoxy-4,4-dimethoxytetrahydro-2H-pyran (2.1 g, 11 mmol) in THF/water (50 mL/10 mL) was added concentrated HCl (6 mL). After being stirred at room temperature for 1 h, the mixture was diluted with EtOAc. The organic layer was separated and the aqueous layer was extracted with ether five times. The combined organic layers were dried over MgSO4, filtered and concentrated to give 1.55 g (97%) of the desired product 1H NMR (CDCl3) δ 4.30-3.50 (7H, m), 2.62-2.57 (2H, m), 1.30-1.20 (3H, t, J=5 Hz). The organic layer was separated the aqueous layer was extracted with ether five times The combined organic layers were dried over MgSO4 filtered concentrated