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[ 51335-75-2 ]
[ 82962-54-7 ]
| Yield | Reaction Conditions | Operation in experiment |
| 78% |
With water; sodium chloride In dimethyl sulfoxide for 20.00 h; Reflux |
The mixture of 2,2-dimethyl-1,3-dioxane-5,5-dicarboxylate S2 (385 g, 1.5 mol), NaCl (105 g, 1.8 mol), water (58g, 3.2 mol) and dimethylsulfoxide (1500 mL) was refluxed for 20 hours. The solution was cooled to room temperature, the saturated solution of NaCl (750 mL) was added and the product was extracted with diethyl ether (4 x 600 mL). Combined organic extracts were washed by brine (2 x 150 mL) and dried over Na2SO4. The solvents were evaporated and the residual oil was distilled yielding 3 (220 g, 78percent) as colorless liquid 3. 1H NMR (700 MHz, CDCl3, 300K): δ = 4.16 (q, J = 7.3 Hz, 2H), 4.01-4.08 (m, 4H), 2.77-2.81(m, 1H), 1.43 (s, 3H), 1.40 (s, 3H), 1.26 (t, J = 7.3 Hz, 3H). |
| 69% |
Stage #1: With potassium hydroxide In ethanol; isopropyl alcohol at 20℃; for 5.00 h; Inert atmosphere
Stage #2: With hydrogenchloride In ethanol; water; isopropyl alcohol at -4℃;
Stage #3: at 90℃; for 16.00 h; |
(4b) Synthesis of diethyl 2,2-dimethyl-l,3-dioxan-5-carboxylate (2). iPotassium hydroxide (15 g, 2.667 mol) was stirred in 1843 mL of anhydrous ethanol and 97 mL of isopropanol to produce a clear solution. To this clear solution was added 1 (527 g, 2.026 mol) in 184 mL of ethanol and 10 mL of isopropanol. The reaction was stirred at room temperature under nitrogen for 5 hours and then evaporated. Water (580 mL) was added and cooled to -4 °C. To this solution was added 58 mL of concentrated HC1 and 1.2 L of 1.0 M HC1 to reach a pH of 2.5 (followed by pH paper). The solution was extracted with ethyl acetate (4 χ 1 L, pH adjusted to 2.5 following each extraction). The combined organics were dried and evaporated to a colorless oil. After the addition of 1.35 L of pyridine, the solution was stirred at 90 °C overnight (16 hours). The solution was distilled at 80 °C (ca. 150 mmHg) to remove the pyridine, and the product was removed by distillation at 55-65 °C (1-2 mmHg), 261.7 g, in 69percent yield. |
| 56% |
With water; sodium chloride In dimethyl sulfoxide at 180℃; for 48.00 h; |
To a stirring solution o? 18.3 (32.0 g , 123,0 mmoL) in DMSO (350 ml) was added NaCi (7.20 g , 123,0 mmoL}: and H20 (4.43g ,246.0 mmoL) and the reaction mixture was heated to 180 C for 48 hour . The mixture was cooled to r.t , diluted with DCM (500 ml), and washed with water (3 x 500 ml) . The organic layer was dried over a-SC and concentrated under reduced pressure to give ISA (12.0 g: 56percent) as a red oil |
| 53% |
With sodium chloride In water; dimethyl sulfoxide for 7.00 h; Heating / reflux |
To the solution of 2,2-dimethyl-[1,3]dioxane-5,5-dicarboxylic acid diethyl ester (19.75 g, 75.96 mmol) in dimethyl sulfoxide (80 ml) was added sodium chloride (4.4 g, 75.76 mmol) and water (2 ml). The reaction was refluxed for 7 h. After such time, it was poured into saturated sodium chloride solution (500 ml) and extracted with ether (4.x.200 ml). The combined organics were washed with water, dried over sodium sulfate, filtered and concentrated in vacuo. The residual oil was distilled under reduced pressure. Three fractions collected between 100° C. and 120° C. were combined to afford 2,2-dimethyl-[1,3]dioxane-5-carboxylic acid ethyl ester (7.58 g, 53percent) as a clear oil (J. Org. Chem. 1986, 51, 2637) 1H NMR (300 MHz, CDCl3) δ ppm 1.26 (t, J=7.1 Hz, 3 H, CH3), 1.41 (s, 3 H, CH3), 1.44 (s, 3 H, CH3), 2.74-2.85 (m, 1 H, CH), 3.96-4.30 (m, 6 H, 3.x.OCH2). |
Reference：
[1] Synlett, 2017, vol. 28, # 5, p. 583 - 588
[2] Chemical and Pharmaceutical Bulletin, 1993, vol. 41, # 2, p. 339 - 345
[3] Journal of the American Chemical Society, 1987, vol. 109, # 26, p. 8071 - 8081
[4] Journal of Organic Chemistry, 1986, vol. 51, # 14, p. 2637 - 2641
[5] Patent: WO2012/103279, 2012, A2. Location in patent: Page/Page column 16-17
[6] Collection of Czechoslovak Chemical Communications, 2007, vol. 72, # 7, p. 965 - 983
[7] Angewandte Chemie - International Edition, 2018, vol. 57, # 2, p. 574 - 578[8] Angew. Chem., 2018, vol. 130, p. 583 - 587,5
[9] Patent: WO2013/170030, 2013, A1. Location in patent: Page/Page column 56
[10] Patent: US2008/21032, 2008, A1. Location in patent: Page/Page column 81
[11] Patent: US4336408, 1982, A
[12] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 24, p. 7358 - 7360
[13] Organic Process Research and Development, 2012, vol. 16, # 9, p. 1527 - 1537
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[ 20605-01-0 ]- [ 82962-54-7 ]
Reference：
[1] Chemical and Pharmaceutical Bulletin, 1993, vol. 41, # 2, p. 339 - 345
[2] Journal of the American Chemical Society, 1987, vol. 109, # 26, p. 8071 - 8081
[3] Journal of Organic Chemistry, 1986, vol. 51, # 14, p. 2637 - 2641
[4] Tetrahedron, 1991, vol. 47, # 6, p. 1001 - 1012
[5] Patent: WO2012/103279, 2012, A2
[6] Organic Process Research and Development, 2012, vol. 16, # 9, p. 1527 - 1537
[7] Patent: WO2013/170030, 2013, A1
[8] Synlett, 2017, vol. 28, # 5, p. 583 - 588
[9] Angewandte Chemie - International Edition, 2018, vol. 57, # 2, p. 574 - 578[10] Angew. Chem., 2018, vol. 130, p. 583 - 587,5
[11] Patent: US2008/21032, 2008, A1
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