Structure of 35005-81-3
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CAS No. : | 35005-81-3 |
Formula : | C9H11NO3 |
M.W : | 181.19 |
SMILES Code : | CCOC(=O)C1=CN=C(CO)C=C1 |
MDL No. : | MFCD12131130 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P264-P270-P301+P312-P330 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With sodium tetrahydroborate; calcium chloride; In tetrahydrofuran; ethanol; at 0℃; for 5.5h; | To a cooled (ice-bath) solution of diethyl pyridine-2, 5-dicarboxylate (10 g, 45 mmol) in a mixture of absolute EtOH (40 ml_) and THF (3.5 ml_) under nitrogen were added NaBH4 (4.26 g, 112 mmol) and anhydrous CaCh (7.86 g, 71 mmol) portion wise over 30 min. The resulting reaction mixture was stirred at 0C for 5 h. The reaction mixture was poured in sat. aq. NH4CI (150 ml_) and extracted with EtOAc (4 x 150 ml_). The combined organic extracts were dried Na2S04) and concentrated. Six other 10 g batches and one 5 g batch were reacted in parallel and the resulting crude material from each reaction was combined and purified by column chromatography with silica gel (60-120 mesh) eluting with 20% EtOAc/hexane to afford the title compound (55 g, 320 mmol, 100%). |
84% | With sodium tetrahydroborate; calcium chloride; In tetrahydrofuran; ethanol; at 0℃; for 12.0h; | To a stirred solution of 24 (2.50 g, 11.20 mmol) in EtOH (300.00 mL) and THF (275.00 mL), CaCl2 (4.97 g, 44.80 mmol) was added. The mixture was cooled to 0 C before adding NaBH4 (0.85 g, 22.40 mmol) portionwise. The reaction was stirred at 0 C for 12 h, then a saturated solution of NH4Cl was added and volatiles were removed under reduced pressure. The aqueous phase was extracted with DCM (3 x 25.00 mL) and the combined organic layers were dried over Na2SO4, filtered and evaporated. The crude was purified by means of chromatography on silica gel (25 % ethyl acetate in petroleum ether) to afford ethyl 6-(hydroxymethyl)nicotinate (84 % yield) as a transparent oil. ESI-MS m/z 182 [M+H]+, 204 [M+Na]+;1H NMR (300 MHz, CDCl3) δ1.41 (t, J = 7.1 Hz, 3H), 3.59 (br s, 1H), 4.42 (q, J = 7.1 Hz,2H), 4.83 (s, 2H), 7.35 (d, J = 8.1 Hz, 1H), 8.29 (d, J = 8.1 Hz, 1H), 9.17 (s, 1H). To a solution of the previously synthesize alcohol (1.70 g, 9.40 mmol) in dry DCM (30.00 mL), cooled to 0 C, SOCl2 (3.42 mL, 47.00 mmol) was added, and the reaction was stirred at 25 C for 2 h. A saturated solution of NaHCO3 was added and the aqueous phase was extracted with DCM (3 x 25.00 mL). The combined organic layers were dried overNa2SO4, filtered and evaporated to afford title compound(quantitative yield) as a yellow oil. ESI-MS m/z 200 [M+H]+, 222 [M+Na]+; 1H NMR (300 MHz, CDCl3) δ 1.41 (t, J = 7.1 Hz, 3H), 4.42 (q, J= 7.1 Hz, 2H), 4.73 (s, 2H), 7.59 (d, J = 8.1 Hz, 1H), 8.34 (dd, J= 8.1, 2.1 Hz, 1H), 9.16 (s, 1H). |
66% | With sodium tetrahydroborate; calcium chloride; In tetrahydrofuran; ethanol; for 3.0h;Inert atmosphere; Cooling with ice; | In an Ar atmosphere, calcium chloride (29.92 g, 269.6 mmol), ethanol (390 mL) and THF (390 mL) were introduced into a reactor, and subsequently sodium borohydride (20.40 g, 539.2 mmol) was introduced to the reactor in divided portions under ice cooling. After sodium borohydride was introduced, the reaction mixture was stirred for 2.5 hours under ice cooling. Compound T (30.09 g, 134.8 mmol) was introduced into the reaction mixture in divided portions under ice cooling, and the reaction mixture was stirred for 30 minutes under ice cooling. The reaction mixture was poured into ice water (1.5 L), and then ammonium chloride (300 g) was added to the reaction mixture with stirring. The target compound was extracted with ethyl acetate (1 L×2). The organic layer was washed sequentially with water (1 L) and saturated brine (1 L). The organic layer was dried over magnesium sulfate, and then the solvent of the organic layer was distilled off under reduced pressure. Thus, compound 9′ (16.12 g, yield 66.0%) as a pale yellow brown solid was obtained. |
62% | With sodium tetrahydroborate; In tetrahydrofuran; ethanol; at 0℃; for 1.0h;Inert atmosphere; | Sodium borohydride (1.27 g, 33.5 mmol) and anhydrous calcium chloride (2.35 g, 21.2 mmol) was added in several portions over 30 minutes to a stirred solution of <strong>[5552-44-3]diethyl pyridine-2,5-dicarboxylate</strong> (3.0 g, 13.4 mmol) in ethanol (12 mL) and THF (6 mL) at 0C under a nitrogen atmosphere. The mixture was allowed to warm to room temperature and stirring continued for one hour then poured into saturated NH4CI solution (150 mL) and extracted with EtOAc (5 x 50 mL). The combined organic extracts were dried (Na2S04) and evaporated under reduced pressure to leave a residue which was purified by column chromatography on silica gel (60- 120 mesh) using 36% EtOAc/hexanes as the eluent to give the title compound (1 .5 g, 62%) as an off-white solid. |
45% | With sodium tetrahydroborate; calcium chloride; In ethanol; at -5℃; for 0.75h; | Example 51 Synthesis of Compound (II-9); Step (1): Compound 9a → Compound 9b; Compound 9a (12.8 g, 57.3 mmol) was dissolved in ethanol, and subsequently cooled to -5C. To the reaction solution was added sodium borohydride (1.41 g, 37.3 mmol), and then calcium chloride (4.14 g, 37.3 mmol) was added small-portion-wise, followed by stirring for 45 minutes. The reaction solution was poured into purified water (120 mL), and then ethanol was concentrated in vacuo. The precipitated solid was filtrated to yield Compound 9b (4.71 g, 45% yield). 1H-NMR (CDCl3) 8(delta): 9.16 (1H, d, J = 1.8 Hz), 8.29 (1H, dd, J = 1.8, 8.4 Hz), 7.35 (1H, d, J = 8.4 Hz), 4.83 (2H, br s), 4.42 (2H, q, J = 6.9 Hz), 3.69 (1H, s), 1.42 (3H, t, J = 6.9 Hz). |
31.33 g (84%) | With sodium borohydrid; calcium chloride; In ethanol; | (a) Ethyl 6-hydroxymethylnicotinate. 45.77 g (205 mmol) of <strong>[5552-44-3]ethyl 2,5-pyridinedicarboxylate</strong> was dissolved in 410 ml of absolute ethanol in a one-liter round-bottomed flask. The reaction medium was cooled to -5 C. and 5.04 g (133.2 mmol) of sodium borohydride was added, followed by portionwise addition of 14.79 g (133.2 mmol) of calcium chloride, while keeping the temperature below -5 C. The reaction medium was stirred at -5 C. for two hours and poured into water. The product was extracted with ethyl ether and washed with water and the organic phase was then dried over magnesium sulfate and evaporated. The residue obtained was purified by chromatography on a column of silica eluted with ethyl ether, in order to obtain 31.33 g (84%) of a white crystalline solid. |
Tags: 35005-81-3 synthesis path| 35005-81-3 SDS| 35005-81-3 COA| 35005-81-3 purity| 35005-81-3 application| 35005-81-3 NMR| 35005-81-3 COA| 35005-81-3 structure
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