* 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.
Reference:
[1] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 24, p. 4399 - 4403
[2] Patent: US2016/75708, 2016, A1, . Location in patent: Paragraph 0104; 0106
[3] Patent: KR2015/139962, 2015, A, . Location in patent: Paragraph 0155; 0158; 0161-0162
2
[ 146256-97-5 ]
[ 146256-98-6 ]
[ 170123-25-8 ]
Reference:
[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1993, # 12, p. 1313 - 1318
3
[ 146256-97-5 ]
[ 170123-25-8 ]
Yield
Reaction Conditions
Operation in experiment
41%
With potassium <i>tert</i>-butylate In toluene at -10 - 0℃; for 1.5 h; Inert atmosphere
To a suspension of potassium tert-butoxide (791 mg, 7.05 mmol) in anhydrous toluene (19 mL) at 10 C a solution of 30 (1.43 g, 4.7 mmol) in toluenewas added dropwise. The reactionwas stirred at 0 C for 90 min and then it was quenched with acetic acid (500 mL), followed by the addition of a cold solution of NaH2-PO4USDH2O (2.5 g) in 25 mL of water. The layers were separated, and the aqueous phase was extracted with CHCl3. The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash chromatography (silica gel, pet. ether/EtOAc 5:1, Rf 0.44) obtaining the title compound 31 as a yellow oil (497 mg, 41percent yield). 1H NMR (CDCl3, 200 MHz) major rotamer: d 4.55 and 4.47 (s, 1H), 4.27-4.22 (m, 2H), 3.91-3.84 (m) and 3.82 (t, J = 8.2 Hz) 2H, 2.69 (t, J = 8.0 Hz, 2H), 1.49 and 1.43 (s, 9H), 1.30 (t, J = 7.1 Hz, 3H). Anal. C12H19NO5 (C, H, N).
Reference:
[1] Chemical Communications, 2016, vol. 52, # 53, p. 8271 - 8274
[2] Journal of the Chemical Society - Perkin Transactions 1, 1997, # 15, p. 2179 - 2187
[3] Organic Letters, 2007, vol. 9, # 21, p. 4255 - 4258
[4] Tetrahedron Asymmetry, 2005, vol. 16, # 13, p. 2243 - 2247
[5] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 6, p. 1931 - 1938
[6] European Journal of Medicinal Chemistry, 2012, vol. 56, p. 96 - 107
[7] Journal of the American Chemical Society, 2003, vol. 125, # 40, p. 12172 - 12178
4
[ 146256-97-5 ]
[ 146256-98-6 ]
[ 170123-25-8 ]
Reference:
[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1993, # 12, p. 1313 - 1318
5
[ 146256-97-5 ]
[ 101385-93-7 ]
Reference:
[1] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 24, p. 4399 - 4403
With potassium tert-butylate; In toluene; at -10 - 0℃; for 1.5h;Inert atmosphere;
To a suspension of potassium tert-butoxide (791 mg, 7.05 mmol) in anhydrous toluene (19 mL) at 10 C a solution of 30 (1.43 g, 4.7 mmol) in toluenewas added dropwise. The reactionwas stirred at 0 C for 90 min and then it was quenched with acetic acid (500 mL), followed by the addition of a cold solution of NaH2-PO4USDH2O (2.5 g) in 25 mL of water. The layers were separated, and the aqueous phase was extracted with CHCl3. The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash chromatography (silica gel, pet. ether/EtOAc 5:1, Rf 0.44) obtaining the title compound 31 as a yellow oil (497 mg, 41% yield). 1H NMR (CDCl3, 200 MHz) major rotamer: d 4.55 and 4.47 (s, 1H), 4.27-4.22 (m, 2H), 3.91-3.84 (m) and 3.82 (t, J = 8.2 Hz) 2H, 2.69 (t, J = 8.0 Hz, 2H), 1.49 and 1.43 (s, 9H), 1.30 (t, J = 7.1 Hz, 3H). Anal. C12H19NO5 (C, H, N).
The Preparation of Compound 14D: Sodium (27.6 g, 0.765 mol) was added stepwise to absolute ethanol (1.5 L). When the solid completely disappeared, compound 14C (300 g, 1.04 mol) was added to the solution. The reaction mixture was refluxed overnight, monitored with TCL (PE/EA=4:1), until the starting material was completely consumed. The reaction mixture was evaporated to remove most of the solvent. The residue was dissolved in water (1 L) and acidified with citric acid to pH 6. The mixture was extracted with EA (1 L×3). The extract liquors were combined, washed with brine (1 L×3), dried with anhydrous Na2SO4 and evaporated, to obtain compound 14D (169 g, 63.4percent) as a brown oily substance. The crude product was used directly in the next step without a further purification.
With sodium ethanolate; In ethanol;Reflux;
Sodium ethoxide (27.6 g, 0.765 mol) was added stepwise to absolute ethanol (1.5 L). When the solid completely disappeared, compound 14C (300 g, 1.04 mol) was added to the solution. The reaction mixture was refluxed overnight, monitored with TCL (PE/EA=4:1), until the starting material was completely consumed. The reaction mixture was evaporated to remove most of the solvent. The residue was dissolved in water (1 L) and acidified with citric acid to pH 6. The mixture was extracted with EA (1 L×3). The extract liquors were combined, washed with brine (1 L×3), dried with anhydrous Na2SO4 and evaporated, to obtain compound 14D (169 g, 63.4percent) as a brown oily substance. The crude product was used directly in the next step without a further purification.