3-methoxy-4-(morpholin-4-ylmethyl)phenol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of NaH (55-65% disp. in oil, 0.30 g, 6.88 mmol) in dry DMF (5 mL) under nitrogen was cooled by a water-bath. A solution of 7A (1.17 g, 5.24 mmol) in DMF (10 mL) was added drop-wise over 15 minutes. The mixture was stirred for one h and then tert-butyl 3-[(methylsulfonyl)oxy]azetidine-1-carboxylate (1.7 g, 6.77 mmol) in DMF (10 mL) was added. The mixture was heated to 80° C. for 3 days and then cooled to RT. Water and some aqueous NaOH were added and the mixture was extracted three times with EtOAc. The combined organic solutions were dried (MgSO4) and evaporated. The residue was purified by column chromatography on SiO2 using 5% triethylamine in EtOAc as eluent. There was obtained 2.1 g (104%) of 7B as a colorless oil. 1H NMR (500 MHz, CDCl3): δ 1.45 (s, 9H), 2.39-2.56 (m, 4H), 3.48 (s, 2H), 3.65-3.75 (m, 4H), 3.79 (s, 3H), 3.95-4.04 (m, 2H), 4.23-4.33 (m, 2H), 4.82-4.91 (m, 1H), 6.19 (d, 1H), 6.38 (s, 1H), 7.21 (d, 1H). was cooled by a water-bath cooled to RT the mixture was extracted three times with EtOAc The combined organic solutions were dried (MgSO4) evaporated The residue was purified by column chromatography on SiO2 using 5% triethylamine in EtOAc as eluent

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of NaH (55-65% disp. in oil, 0.30 g, 6.88 mmol) in dry DMF (5 mL) under nitrogen was cooled by a water-bath. A solution of 7A (1.17 g, 5.24 mmol) in DMF (10 mL) was added drop-wise over 15 minutes. The mixture was stirred for one h and then tert-butyl 3-[(methylsulfonyl)oxy]azetidine-1-carboxylate (1.7 g, 6.77 mmol) in DMF (10 mL) was added. The mixture was heated to 80° C. for 3 days and then cooled to RT. Water and some aqueous NaOH were added and the mixture was extracted three times with EtOAc. The combined organic solutions were dried (MgSO4) and evaporated. The residue was purified by column chromatography on SiO2 using 5% triethylamine in EtOAc as eluent. There was obtained 2.1 g (104%) of 7B as a colorless oil. 1H NMR (500 MHz, CDCl3): δ 1.45 (s, 9H), 2.39-2.56 (m, 4H), 3.48 (s, 2H), 3.65-3.75 (m, 4H), 3.79 (s, 3H), 3.95-4.04 (m, 2H), 4.23-4.33 (m, 2H), 4.82-4.91 (m, 1H), 6.19 (d, 1H), 6.38 (s, 1H), 7.21 (d, 1H). was cooled by a water-bath cooled to RT the mixture was extracted three times with EtOAc The combined organic solutions were dried (MgSO4) evaporated The residue was purified by column chromatography on SiO2 using 5% triethylamine in EtOAc as eluent

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4-hydroxy-2-methoxybenzaldehyde (1.0 g, 6.57 mmol) and morpholine (2.0 g, 23.0 mmol) in 50 ml dichloroethane was stirred at rt for 1 h. Sodium triacetoxyborohydride (2.0 g, 9.44 mmol) was added in portions over 20 minutes. The reaction mixture was stirred at rt over night. Aqueous NaHCO3 (sat.) was added, the phases were separated and the aqueous phase was extracted with DCM once. The solvent was removed by evaporation and the residue was purified by column chromatography on SiO2 using 5% triethylamine in EtOAc as eluent. There was obtained 1.19 g (81%) of 7A iii as a solid. 1H NMR (500 MHz, CDCl3): δ 2.41-2.71 (m, 4H), 3.52 (s, 2H), 3.72 (s, 3H), 3.69-3.79 (m, 4H), 6.27 (d, 1H), 6.32 (s, 1H), 7.10 (d, 1H). The reaction mixture was stirred at rt over night the phases were separated the aqueous phase was extracted with DCM once The solvent was removed by evaporation the residue was purified by column chromatography on SiO2 using 5% triethylamine in EtOAc as eluent

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of NaH (55-65% disp. in oil, 0.30 g, 6.88 mmol) in dry DMF (5 mL) under nitrogen was cooled by a water-bath. A solution of 7A (1.17 g, 5.24 mmol) in DMF (10 mL) was added drop-wise over 15 minutes. The mixture was stirred for one h and then tert-butyl 3-[(methylsulfonyl)oxy]azetidine-1-carboxylate (1.7 g, 6.77 mmol) in DMF (10 mL) was added. The mixture was heated to 80° C. for 3 days and then cooled to RT. Water and some aqueous NaOH were added and the mixture was extracted three times with EtOAc. The combined organic solutions were dried (MgSO4) and evaporated. The residue was purified by column chromatography on SiO2 using 5% triethylamine in EtOAc as eluent. There was obtained 2.1 g (104%) of 7B as a colorless oil. 1H NMR (500 MHz, CDCl3): δ 1.45 (s, 9H), 2.39-2.56 (m, 4H), 3.48 (s, 2H), 3.65-3.75 (m, 4H), 3.79 (s, 3H), 3.95-4.04 (m, 2H), 4.23-4.33 (m, 2H), 4.82-4.91 (m, 1H), 6.19 (d, 1H), 6.38 (s, 1H), 7.21 (d, 1H). was cooled by a water-bath cooled to RT the mixture was extracted three times with EtOAc The combined organic solutions were dried (MgSO4) evaporated The residue was purified by column chromatography on SiO2 using 5% triethylamine in EtOAc as eluent

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4-hydroxy-2-methoxybenzaldehyde (1.0 g, 6.57 mmol) and morpholine (2.0 g, 23.0 mmol) in 50 ml dichloroethane was stirred at rt for 1 h. Sodium triacetoxyborohydride (2.0 g, 9.44 mmol) was added in portions over 20 minutes. The reaction mixture was stirred at rt over night. Aqueous NaHCO3 (sat.) was added, the phases were separated and the aqueous phase was extracted with DCM once. The solvent was removed by evaporation and the residue was purified by column chromatography on SiO2 using 5% triethylamine in EtOAc as eluent. There was obtained 1.19 g (81%) of 7A iii as a solid. 1H NMR (500 MHz, CDCl3): δ 2.41-2.71 (m, 4H), 3.52 (s, 2H), 3.72 (s, 3H), 3.69-3.79 (m, 4H), 6.27 (d, 1H), 6.32 (s, 1H), 7.10 (d, 1H). The reaction mixture was stirred at rt over night the phases were separated the aqueous phase was extracted with DCM once The solvent was removed by evaporation the residue was purified by column chromatography on SiO2 using 5% triethylamine in EtOAc as eluent

反応条件: temp:0.00; pressure:0.00; stir: