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With lithium hydroxide monohydrate; water In 1,4-dioxane; methanol at 20℃;
Example B10 A solution of methyl 4-methyltetrahydro-2H-pyran-4-carboxylate (5.00 g, 31.6 mmol) in 1:1:1 dioxane/water/MeOH (60 mL) was treated with lithium hydroxide hydrate (5.31 g, 126 mmol) and stirred at RT overnight. The mixture was partially concentrated, diluted with water and EtOAc and acidified to pH=1 with 6M HCl. The layers were separated, the aqueous layer extracted with additional EtOAc (50 mL) and the combined organics were washed with brine, dried over Na2SO4 and concentrated to dryness to afford 4-methyltetrahydro-2H-pyran-4-carboxylic acid (4.61 g, 100percent). 1H NMR (400 MHz, DMSO-d6): δ 12.29 (s, 1H), 3.65 (dt, J=11.8, 4.3 Hz, 2H), 3.33-3.32 (m, 2H), 1.87-1.86 (m, 2H), 1.35 (ddd, J=13.5, 9.9, 4.1 Hz, 2H), 1.13 (s, 3H).
100%
With water; lithium hydroxide In 1,4-dioxane; methanol at 20℃;
Example B24 A solution of methyl 4-methyltetrahydro-2H-pyran-4-carboxylate (5.00 g, 31.6 mmol) in 1:1:1 dioxane/water/MeOH (60 mL) was treated with lithium hydroxide hydrate (5.31 g, 126 mmol) and stirred at RT overnight. The mixture was partially concentrated, diluted with water and EtOAc and acidified to pH=1 with 6M HCl. The layers were separated, the aqueous layer extracted with additional EtOAc (50 mL) and the combined organics were washed with brine, dried over Na2SO4 and concentrated to dryness to afford 4-methyltetrahydro-2H-pyran-4-carboxylic acid (4.61 g, 100percent). 1H NMR (400 MHz, DMSO-d6): δ 12.29 (s, 1H), 3.65 (dt, J=11.8, 4.3 Hz, 2H), 3.33-3.32 (m, 2H), 1.87-1.86 (m, 2H), 1.35 (ddd, J=13.5, 9.9, 4.1 Hz, 2H), 1.13 (s, 3H).
In a 30 ml glass flask equipped with a stirrer, a thermometer and a dropping funnel, 0.8 g (6.4 mmol) of 4-methyl-4-cyanotetrahydropyran and 3.5 ml (2.8 mmol) of 8 mol/l sodium hydroxide aqueous solution were added, and the mixture was stirred at 100°C for 8 hours. After completion of the reaction, 12 mmol/l hydrochloric acid 3.0 ml (36 mmol), 40 ml of water and 50 ml of chloroform were added to the obtained reaction solution, under ice cooling. The organic layer was separated. The aqueous layer was extracted with 50 ml of diethyl ether, combined with the above organic layer and dried over anhydrous magnesium sulfate. After filtration, it was concentrated under reduced pressure, as a light yellow solid, to obtain 0.72 g of 4-methyltetrahydropyran-4-carboxylic acid (isolation yield: 78percent).
Stage #1: With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at 0 - 50℃; for 3.41667 h; Stage #2: at 0 - 20℃; Stage #3: With water; citric acid In tetrahydrofuran; hexane
Description 9. 4-methyltetrahydro-2H-pyran-4-carboxylic acid. (D9); Diisopropylamine (6.37 ml_, 44.7 mmol) in THF (50 ml.) was cooled to 0 0C under argon. N-Butyllithium (16.7 ml_, 2.5 M in hexane, 41.7 mmol) was added dropwise over 10 min. The reaction mixture was left to stir for 15 min at 0 0C. A solution of tetrahydro-2H-pyran- 4-carboxylic acid (D8) (1.94 g, 14.9 mmol) in THF (1OmL) was added and a white precipitate was formed. The resulting mixture was then heated at 50 0C for 3 h. The reaction mixture was cooled to 0 0C and methyl iodide (2.80 ml_, 44.7 mmol) was added dropwise. The reaction was then allowed to warm to rt and left to stir overnight. 10percent aqueous citric acid solution (40 ml.) was then added and the THF was removed by rotary evaporation. The residual aqueous mixture was extracted with Et2O (2x). The organics were combined, dried (Na2SO4) and concentrated by rotary evaporation to give the title compound (D9) (1.26 g, 53percent) as a yellow solid.
1.05 g
Stage #1: With lithium diisopropyl amide In tetrahydrofuran at 50℃; for 3 h; Inert atmosphere; Cooling with ice Stage #2: at 20℃; for 19 h; Inert atmosphere; Cooling with ice
(1) To a solution of Compound 1 (1.3 g) in tetrahydrofuran (20 mL) was added dropwise a solution of lithiumdiisopropylamide-tetrahydrofuran (2 mol/mL, 14 mL) under nitrogen atmosphere under ice-cooling, and then the mixture was stirred at 50°C for 3 hours. To the reaction mixture was added dropwise methyl iodide (1.87 mL) under ice-cooling, and the mixture was stirred at room temperature for 19 hours. To the reaction mixture was added a 10percent aqueous solution of citric acid (20 mL), stirred, then tetrahydrofuran was evaporated under reduced pressure, and extracted with ethyl acetate. The organic layer was dried, and concentrated under reduced pressure. The residue was purified with silica gel column chromatography (hexane:ethyl acetate=80:20-50:50) to give Compound 2 (1.05 g) as a pale brown powder. To a solution of Compound 2 (896 mg) in toluene (37 mL) were added triethylamine (1.12 mL) and Compound 3 (1.39 mL), and the mixture was stirred under nitrogen atmosphere at 85°C for 17 hours. To the reaction solution was added dropwise an aqueous solution of sodium hydroxide (1 mol/mL, 27 mL) under ice-cooling, ethyl acetate and water were added thereto, and then the organic layer was separated. The resultant organic layer was dried, and concentrated under reduced pressure to give a crude material of Compound 4 (671 mg) as a brown viscous material. To a solution of Compound 4 (665 mg) in tetrahydrofuran (55 mL) was added a mixed solution of concentrated hydrochloric acid (3.05 mL) and water (5.5mL), and the mixture was stirred at room temperature for 48 hours. The reaction solution was concentrated under reduced pressure to give a crude material of Compound 5 (558 mg) as a pale brown powder. MS (ESI): m/z 116 [M+H]+
In a 30 ml glass flask equipped with a stirrer, a thermometer and a dropping funnel, 0.8 g (6.4 mmol) of <strong>[856255-87-3]4-methyl-4-cyanotetrahydropyran</strong> and 3.5 ml (2.8 mmol) of 8 mol/l sodium hydroxide aqueous solution were added, and the mixture was stirred at 100C for 8 hours. After completion of the reaction, 12 mmol/l hydrochloric acid 3.0 ml (36 mmol), 40 ml of water and 50 ml of chloroform were added to the obtained reaction solution, under ice cooling. The organic layer was separated. The aqueous layer was extracted with 50 ml of diethyl ether, combined with the above organic layer and dried over anhydrous magnesium sulfate. After filtration, it was concentrated under reduced pressure, as a light yellow solid, to obtain 0.72 g of 4-methyltetrahydropyran-4-carboxylic acid (isolation yield: 78%).
1,3-dioxoisoindolin-2-yl 4-methyltetrahydro-2H-pyran-4-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
85%
With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃; for 0.5h;
2.1 General procedure A for preparation of redox-active NHPI esters
General procedure: NHPI esters were prepared according to a previously reported procedure[1]. Around-bottom flask was charged with (if solid) carboxylic acid (1.0 equiv.),N-hydroxyphthalimide (1.0 - 1.1 equiv.) and DMAP (0.1 equiv.). Dichloromethanewas added (0.2- 0.4 M), and the mixture was stirred vigorously. Carboxylic acid (1.0equiv.) was added via syringe (if liquid). DIC (1.1 equiv.) was then added dropwisevia syringe, and the mixture was allowed to stir until the acid was consumed(determined by TLC). Typical reaction times were between 0.5 to 3 h. The mixturewas filtered through a fritted funnel and rinsed with additional CH2Cl2/Et2O. Thesolvent was removed under reduced pressure, and purification by column chromatography afforded the corresponding activated esters, which were used withoutfurther purification unless otherwise noted. Note: Some esters are prone to hydrolysison silica gel during column chromatography and should be purified as quickly aspossible to avoid decomposition.
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