1-BOC-4-甲磺酰基氧甲基哌啶

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

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: 1,1-Dimethylethyl 4-[({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate (0.34 g, 95%) was prepared as a white solid from 6-[4-(methylsulfonyl)phenyl]-3-pyridinol (Example 146, Step 4, 0.20 g, 0.80 mmol), 1,1-dimethylethyl 4-{[(methylsulfonyl)oxy]methyl}-1-piperidinecarboxylate (0.33 g, 1.12 mmol), K2CO3 (0.23 g, 1.60 mmol) in DMF (7 mL) in a manner similar to Example 139, Step 3. The reaction mixture was cooled to ambient temperature, and poured into water (50 mL). The precipitate was collected and washed with water, air dried to give 1,1-dimethylethyl 4-[({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.40 (bs, 1H), 8.14 (d, 2H, J=7.5 Hz), 8.01 (d, 2H, J=7.3 Hz), 7.80-7.70 (m, 1H), 7.34 (bs, 1H), 4.18 (bs, 2H), 3.91 (d, 2H, J=6.1 Hz), 3.07 (s, 3H), 2.85-2.65 (m, 2H), 2.10-1.95 (m, 1H), 1.90-1.80 (m, 2H), 1.45 (s, 9H), 1.40-1.20 (m, 2H); LRMS (ESI), m/z 447 (M+H). The precipitate was collected washed with water, air dried

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

实验步骤: A mixture of N-Boc-4-piperidinemethanol (1.0 g, 4.51 mmol), Et3N (1.30 mL, 9.01 mmol) in CH2Cl2 (20 mL) at 0° C. was treated dropwise with methanesulfonyl chloride (0.39 mL, 4.96 mmol). The reaction mixture was stirred at 0° C. to 5° C. for 1.5 h, was diluted with CH2Cl2 (100 mL) and washed with 1M NaH2PO4 (50 mL×2) and brine (25 mL). The CH2Cl2 layer was dried over Na2SO4, filtered, and the filtrate was concentrated to a brown oil, which solidified upon cooling to give 1.35 g (100%) of 1,1-dimethylethyl 4-{[(methylsulfonyl)oxy]methyl}-1-piperidinecarboxylate as a brown solid, which was used without further purification. 1H NMR (400 MHz, CDCl3): δ 4.20-4.10 (m, 2H), 4.04 (d, 2H, J=6.5 Hz), 2.99 (s, 3H), 2.75-2.60 (m, 2H), 1.95-1.85 (m, 1H), 1.75-1.65 (m, 2H), 1.43 (s, 9H), 1.30-1.10 (m, 2H). washed with 1M NaH2PO4 (50 mL×2) and brine (25 mL) The CH2Cl2 layer was dried over Na2SO4 filtered the filtrate was concentrated to a brown oil, which upon cooling

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: t-Butyl 4-methylsulfonyloxymethyl-1-piperidinecarboxylate (0.50 g, 1.7 mmol) was dissolved in dimethylformamide (8 ml). To the solution were added potassium iodide (0.37 g), benzimidazole (0.26 g) and 60% sodium hydride in mineral oil (0.088 g), successively, and the mixture was stirred at 60° C. for 2 hours. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate twice. The organic layer was washed with water three times, dried over magnesium sulfate and concentrated under reduced pressure. The resulting solid materials were recrystallized from ethyl acetate/hexane to give the titled compound (0.45 g, 1.4 mmol, Yield 82%). the mixture was extracted with ethyl acetate twice The organic layer was washed with water three times dried over magnesium sulfate concentrated under reduced pressure The resulting solid materials were recrystallized from ethyl acetate/hexane

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: t-butyl 4-Hydroxymethyl-1-piperidinecarboxylate (5.00 g, 23.2 mmol) was dissolved in tetrahydrofuran (75 ml). To the solution were added triethylamine (2.83 g) and methanesulfonyl chloride (3.19 g) under ice cooling, and the mixture was stirred at 0° C. for 5 hours. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate twice. The organic layer was washed with 1N-hydrochloric acid and a saturated aqueous solution of sodium hydrogencarbonate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting solid materials were washed with hexane to give the titled compound (6.55 g, 22.3 mmol, Yield 96%). the mixture was extracted with ethyl acetate twice The organic layer was washed with 1N-hydrochloric acid a saturated aqueous solution of sodium hydrogencarbonate, dried over anhydrous magnesium sulfate concentrated under reduced pressure The resulting solid materials were washed with hexane

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of the title compound from Step B (1.0 g, 3.408 mmoles) in DMF (15 mL) was added to a stirred solution of NaH (0.27 g, 6.817 mmoles) and imidazole (0.464 g, 6.817 mmoles) in DMF (15 mL) under nitrogen atmosphere. The mixture was stirred at 60° C. for 16 h. DMF was evaporated in vacuo. The resulting crude product was extracted with CH2Cl2 and the extract was successively washed with water and brine, and the CH2Cl2 was evaporated to leave the title residue which was chromatographed on silica gel using 3% (10% conc NH4OH in methanol)-CH2Cl2 as eluant to give the title compound (0.823 g). FABMS (M+1)=266.2, δH (CDCl3) 0.8-1.0 (m, 2H), 1.2 (s, 9H), 1.2-1.4 (m, 1H), 1.65 (m, 1H), 2.4 (dt, 2H), 3.6 (d, 2H), 4.8 (d, 2H), 6.7 (s, 1H), 6.8 (s, 1H), 7.2 (s, 1H). DMF was evaporated in vacuo The resulting crude product was extracted with CH2Cl2 the extract was successively washed with water and brine the CH2Cl2 was evaporated