* 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, 2005, vol. 13, # 23, p. 6309 - 6323
[2] Patent: WO2013/157792, 2013, A1,
2
[ 3618-03-9 ]
[ 6297-22-9 ]
Yield
Reaction Conditions
Operation in experiment
81%
With pyridinium chlorochromate In dichloromethane at 20℃;
The 4-hydroxy methyl ester from above (4.147 g; 26.21 mmol) was dissolved in 150 mL DCM and pyridinium chlorochromate (PCC) (8.476 g; 39.32 mmol) was added. The reaction mixture was allowed to stir at room temperature overnight. The reaction mixture was diluted with ether and decanted. Solvents were removed and the residue was purified by flash column chromatography using 25percent EtOAc in hexanes mixture as eluent. The product was obtained as a colorless oil (3.317 g; 81percent yield).
97.5%
With sodium acetate; pyridinium chlorochromate In dichloromethane
EXAMPLE 2 To 400 ml of dry dichloromethane was added 24 g of oven dried Celite, 11.4 g of sodium acetate and 90.5 g of pyridinium chlorochromate with stirring. An additional 350 ml of methylene chloride was added followed by the addition of 44.5 of of methyl 4-hydroxycyclohexanecarboxylate in 40 ml of dichloromethane with a syringe. After 3.5 hours, 800 ml of ether was added with stirring and the mixture was suction filtered through 250 g of silica gel and the solid was washed four times with ether. The combined filtrates were concentrated to a green oil which was taken up in 150 ml of ether and again suction filtered through 50 g of silica gel and the silica gel was rinsed with ether. The combined filtrates were concentrated to a clear oil which was Kugelrohr distilled at 65°-85° C./ca. 1 mm to yield 42.6 g (97.5percent) of methyl 4-oxocyclohexanecarboxylate. 1 H MNR (CDCl3, 60 MHz) δ 3.70 (s, 3H); 2.9-1.8 (9 H).
97.5%
With sodium acetate; pyridinium chlorochromate In dichloromethane
EXAMPLE 2 To 400 ml of dry dichloromethane was added 24 g of oven dried Celite, 11.4 g of sodium acetate and 90.5 g of pyridinium chlorochromate with stirring. An additional 350 ml of methylene chloride was added followed by the addition of 44.5 of of methyl 4-hydroxycyclohexanecarboxylate in 40 ml of dichloromethane with a syringe. After 3.5 hours, 800 ml of ether was added with stirring and the mixture was suction filtered through 250 g of silica gel and the solid was washed four times with ether. The combined filtrates were concentrated to a green oil which was taken up in 150 ml of ether and again suction filtered through 50 g of silica gel and silica gel was rinsed with ether. The combined filtrates were concentrated to a clear oil which was Kugelrohr distilled at 65-85°C/ca. 1 mm to yield 42.6 g (97.5percent) of methyl 4-oxocyclohexanecarboxylate. 1H MNR (CDCl3, 60 MHz) δ 3.70 (s, 3H); 2.9-1.8 (9 H).
1.9 g
With sodium acetate; pyridinium chlorochromate In dichloromethane at 20℃; for 7 h;
Step 2: Methyl 4-oxocyclohexanecarboxylate 0.75 g of sodium acetate, 9.92 g of pyridine chlorochromate and 2.4 g of Celite were added to 50 mL of dichloromethane. 4.7 g of the methyl 4-hydroxycyclohexanecarboxylate prepared in step 1 was dissolved in 15 mL of dichloromethane, and then added dropwise to the above mixture at room temperature for 20 minutes, followed by stirring at room temperatrure for 7 hours. After the reaction, the residual solid was removed by filtration, and the organic layer was washed with 100 mL of water. The organic layer was dried by using anhydrous magnesium sulfate, concentrated and then separated by column chromatography (ethyl acetate: n-hexane = 1 :3) to obtain 1.9 g of the title compound. NMR(300MHz, CDC13) δ 3.73(s, 3H), 2.79~2.78(m, 1H), 2.50~2.37(m, 4H), 2.22-2.21 (m, 2H), 2.05~2.02(m, 2H).
Reference：
[1] Journal of Organic Chemistry, 1991, vol. 56, # 5, p. 1758 - 1763
[2] Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 23, p. 6309 - 6323
[3] Tetrahedron, 2006, vol. 62, # 42, p. 10000 - 10004
[4] Patent: US2010/9964, 2010, A1, . Location in patent: Page/Page column 73
[5] Farmaco, Edizione Scientifica, 1984, vol. 39, # 12, p. 1024 - 1037
[6] Bulletin de la Societe Chimique de France, 1969, p. 781 - 787
[7] Canadian Journal of Chemistry, 1982, vol. 60, p. 1996 - 2001
[8] Journal of Organic Chemistry, 1986, vol. 51, # 12, p. 2218 - 2227
[9] Patent: US4954489, 1990, A,
[10] Patent: US4748274, 1988, A,
[11] Patent: EP270843, 1991, B1,
[12] Journal of Medicinal Chemistry, 2010, vol. 53, # 1, p. 481 - 491
[13] Journal of Medicinal Chemistry, 2012, vol. 55, # 5, p. 2376 - 2387
[14] Patent: WO2013/157792, 2013, A1, . Location in patent: Page/Page column 22-23
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
Life Science
For Research Only
100K+ Compounds
Competitive Price
1-2 Day Shipping
