Name: 4771-80-6|Cyclohex-3-enecarboxylic acid|98%
Brand: Ambeed
SKU: A894968
Price: 5.0 USD
Availability: InStock
Rating: 90 (27 reviews)

1
[ 67-56-1 ]
[ 4771-80-6 ]
[ 6493-77-2 ]

Yield	Reaction Conditions	Operation in experiment
98.6%	With thionyl chloride In methanol at 0 - 5℃; for 4h; Reflux;	1 Add 300mL methanol and 126g cyclohex-3-enecarboxylic acid (1-1) to a 500mL reaction flask,Stir to dissolve, control the temperature 0 ~ 5 ,180 g of thionyl chloride was slowly added, and after the addition, the temperature was raised to reflux, and the reaction was carried out for 4 hours.The completion of the reaction was followed by TLC, and the solvent was removed by concentration.The obtained residue was dissolved in 150 mL of ethyl acetate, washed with 5% sodium bicarbonate solution, dried and concentrated,138 g of methyl cyclohex-3-enecarboxylate (1-2) were obtained, yield: 98.6%.
90%	With sulfuric acid Reflux;
	With sulfuric acid

Reference： [1]Current Patent Assignee: WIND FIRE WHEEL SHANGHAI BIOTECHNOLOGY LTD - CN114181077, 2022, A Location in patent: Paragraph 0060-0064
[2]Location in patent: experimental part Srinivasula Reddy; Gangi Reddy; Ram Reddy; Lingappa; Krishna Rao; Damu; Lee, Yong-Ill [Bulletin of the Korean Chemical Society, 2010, vol. 31, # 6, p. 1732 - 1734]
[3]Current Patent Assignee: POLYMERISABLE PRODUCTS - US2563206, 1946, A

2
[ 4771-80-6 ]
[ 932-67-2 ]

Yield	Reaction Conditions	Operation in experiment
87%	With thionyl chloride Ambient temperature;
81%	With thionyl chloride at 70℃; for 3h;
80.9%	With thionyl chloride In benzene Heating;

	With thionyl chloride
	With thionyl chloride In benzene
	With oxalyl dichloride In toluene for 18h; Ambient temperature;
19.3 g	With thionyl chloride
	With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 1.25h;
	With thionyl chloride at 80℃; for 3h; Schlenk technique; Inert atmosphere; Reflux;

Reference： [1]Legraverend; Boumchita; Bisagni [Journal of Heterocyclic Chemistry, 1990, vol. 27, # 6, p. 1801 - 1804]
[2]Gaudreault, Philippe; Drouin, Christian; Lessard, Jean [Canadian Journal of Chemistry, 2005, vol. 83, # 6-7, p. 543 - 545]
[3]Gramenitskaya, V. N.; Inozemtseva, L. V.; Koz'mina, E. A.; Vul'fson, N. S. [Journal of Organic Chemistry USSR (English Translation), 1982, vol. 18, p. 2260 - 2267][Zhurnal Organicheskoi Khimii, 1982, vol. 18, # 12, p. 2561 - 2570]
[4]Gillois-Doucet [Annales de Chimie (Cachan, France), 1955, vol. <12> 10, p. 497,531] Bergmann; Herman [Journal of Applied Chemistry, 1953, vol. 3, p. 42,48]
[5]Slaugh,L.H. [Journal of the American Chemical Society, 1965, vol. 87, p. 1522 - 1526]
[6]Suto; Stier; Werbel; Arundel-Suto; Leopold; Elliott; Sebolt-Leopold [Journal of Medicinal Chemistry, 1991, vol. 34, # 8, p. 2484 - 2488]
[7]Bastable, John W.; Cooper, Anthony J.; Dunkin, Ian R.; Hobson, John D.; Riddell, William D. [Journal of the Chemical Society. Perkin transactions I, 1981, p. 1339 - 1345]
[8]Lin, Xichen; Artman III, Gerald D.; Stien, Didier; Weinreb, Steven M. [Tetrahedron, 2001, vol. 57, # 42, p. 8779 - 8791]
[9]Artman III, Gerald D.; Waldman, Jacob H.; Weinreb, Steven M. [Synthesis, 2002, # 14, p. 2057 - 2063]
[10]Davies, Jacob; Svejstrup, Thomas D.; Fernandez Reina, Daniel; Sheikh, Nadeem S.; Leonori, Daniele [Journal of the American Chemical Society, 2016, vol. 138, # 26, p. 8092 - 8095]

3
[ 4771-80-6 ]
[ 19914-91-1 ]

Yield	Reaction Conditions	Operation in experiment
94%	With N-Bromosuccinimide In dichloromethane at 20℃; for 7h; Darkness; Molecular sieve;
70%	With lead(IV) acetate; zinc dibromide
70%	With lead(IV) acetate; zinc dibromide In 1,2-dimethoxyethane

51%	With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; water; potassium hydroxide at -10 - 0℃; for 4h; Inert atmosphere;
42%	With lead(IV) acetate; zinc dibromide In 1,2-dimethoxyethane at 0℃; for 0.5h;
	With sodium carbonate Behandeln des Reaktionsgemisches mit Brom;

Reference： [1]Location in patent: experimental part Chen, Feng; Jiang, Xiaojian; Er, Jun Cheng; Yeung, Ying-Yeung [Tetrahedron Letters, 2010, vol. 51, # 26, p. 3433 - 3435]
[2]Iwata, Chuzo; Tanaka, Akira; Mizuno, Hiroaki; Miyashita, Kazuyuki [Heterocycles, 1990, vol. 31, # 6, p. 987 - 991]
[3]Miyashita, Kazuyuki; Tanaka, Akira; Mizuno, Hiroaki; Tanaka, Masahiro; Iwata, Chuzo [Journal of the Chemical Society. Perkin transactions I, 1994, # 7, p. 847 - 852]
[4]Michida, Makoto; Ishikawa, Hideaki; Kaneda, Takeshi; Tatekabe, Shinya; Nakamura, Yoshitaka [Organic Process Research and Development, 2019, vol. 23, # 4, p. 524 - 534]
[5]Motohashi, Shigeyasu; Satomi, Masakichi; Fujimoto, Yasuo; Tatsuno, Takashi [Heterocycles, 1985, vol. 23, # 8, p. 2035 - 2039]
[6]Grewe et al. [Chemische Berichte, 1956, vol. 89, p. 1978,1986]

4
[ 4771-80-6 ]
[ 19914-92-2 ]

Yield	Reaction Conditions	Operation in experiment
97%	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With sodium hydrogencarbonate Stage #2: With iodine; potassium iodide at 20℃; for 16h;
96%	With iodine; sodium hydrogencarbonate; potassium iodide In water at 20℃; for 24h;
96%	With iodine; sodium hydrogencarbonate; potassium iodide In water at 20℃; for 16h;

94%	With iodine; sodium hydrogencarbonate; potassium iodide In water at 21℃; for 21h;
93%	With iodine; sodium hydrogencarbonate; potassium iodide In water at 20℃;
92%	With iodine; sodium hydrogencarbonate; potassium iodide at 20℃; for 3h;
80%	With iodine; sodium hydrogencarbonate; potassium iodide In water
71%	With lead(IV) acetate; sodium iodide In 1,2-dimethoxyethane at 0℃; for 0.5h;
	With iodine; sodium hydrogencarbonate; potassium iodide Lichtausschluss;
	With potassium triiodide; sodium hydrogencarbonate
	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With sodium hydrogencarbonate Stage #2: With iodine; potassium iodide In water
	With iodine; sodium hydrogencarbonate; sodium iodide at 20℃;
	With iodine; potassium iodide	2.B Method B: Synthesis of ethyl (1R,5/?)5-hydroxycyclohex-3-ene carboxylate; The title compound was prepared, in racemic form, by generating (1fi, 3R, 4R)-4-iodocyclohexane-1,3-carbolactone from cyclohex-3-ene carboxylic acid, which was then treatedwith the base DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) to eliminate HI. The resultant (1R,5S*)-cyclohex-3-ene-1,5-carbolactone was then treated with potassium hydroxide dissolved inethanol to yield the title compound (Marshall, J. A., and Shiping, X., 1995)
	With iodine; sodium hydrogencarbonate; potassium iodide In water at 20℃; for 72h;	48 (1S,4S,5S)-4-lodo-6-oxa-bicyclo[3.2.1]octan-7-one and (1 R,4R,5R)-4-iodo-6- oxa-bicyclo[3.2.1]octan-7-one. To a stirred mixture of racemic cyclohex-3- enecarboxylic acid (5 g, 39.6 mmol), sodium bicarbonate (10 g, 119 mmol), and water (100 ml) a solution of iodine (10.7 g, 42.1 mmol) and potassium iodide (39.7 g, 239,2 mmol) in water (100 ml) was added in one portion at room temperature. The flask was immediately covered with aluminum foil and the resulting mixture was stirred at room temperature for three days. The desired product (9.2 g of a racemic (1 :1 ) mixture) was collected by filtration as a white solid.
	With iodine; sodium hydrogencarbonate; potassium iodide In water for 24h; Darkness; Inert atmosphere;	4.6. Methyl (+/-)-(1R,5R)-5-hydroxy-3-cyclohexene-1-carboxylate 1 (+/-)-3-Cyclohexene carboxylic acid (500 mg, 3.96 mmol) was dissolved in a solution of NaHCO3 (1.00 g in 10 mL, 3 equiv) in water. Then a solution of I2 (1.06 g, 1.05 equiv) and KI (3.94 g, 6 equiv) in 10 mL of water was added and the flask protected from light. After 24 h, it was extracted with CH2Cl2, washed successively with Na2S2O3 and NaHCO3 water solutions, dried over anhydrous Na2SO4, and the solvent was evaporated. The crude was re-dissolved in 24 mL of dry toluene under nitrogen atmosphere, and 1.8 mL (1.5 equiv) of DBU was added. The reaction was heated at reflux for 6 h. Then it was filtered on Celite and concentrated. The crude was re-dissolved in 5 mL of dry MeOH and NaOMe added. After 30 min, this was neutralized with Amberlite IR-120, filtered, concentrated, and purified by column chromatography on silica gel (n-hexane/EtOAc 5:5) to yield compound 1 (1.20 g, 96%). Spectroscopic data of this compound were identical to those reported in Ref. 13c.
	With iodine; sodium hydrogencarbonate; potassium iodide In water at 20℃; for 12h;
	With iodine; potassium iodide	E ixycyclohex-3-enecarboxylic acid - Feed E The title compound was prepared, in racemic form, by generating (1 ft, 3ft, 4ft)-4- iodocyclohexane-1 ,3-carbolactone from cyclohex-3-ene carboxylic acid, which was then treated with the base DBU (1 ,8-diazabicyclo[5.4.0]undec-7-ene) to eliminate HI. The resultant (1ft, 5S*)-cyclohex-3-ene-1 ,5-carbolactone was then treated with potassium hydroxide dissolved in ethanol to yield the title compound (Marshall, J. A., and Shiping, X., 1995)

Reference： [1]Barral, Karine; Courcambeck, Jérôme; Pèpe, Gérard; Balzarini, Jan; Neyts, Johan; De Clercq, Erik; Camplo, Michel [Journal of Medicinal Chemistry, 2005, vol. 48, # 2, p. 450 - 456]
[2]Hatcher, Mark A.; Peleg, Sara; Dolan, Patrick; Kensler, Thomas W.; Sarjeant, Amy; Posner, Gary H. [Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 12, p. 3964 - 3976]
[3]Location in patent: scheme or table Goss, Rebecca J. M.; Lanceron, Simon; Roy, Abhijeet Deb; Sprague, Simon; Nur-e-Alam, Mohammed; Hughes, David L.; Wilkinson, Barrie; Moss, Steven J. [ChemBioChem, 2010, vol. 11, # 5, p. 698 - 702]
[4]Bartlett,P.A.; Mcquaid,L.A. [Journal of the American Chemical Society, 1984, vol. 106, p. 7854]
[5]Yu, Seok-Ho; Chung, Sung-Kee [Tetrahedron Asymmetry, 2004, vol. 15, # 4, p. 581 - 584]
[6]Location in patent: scheme or table Nagata, Tsutomu; Nagamochi, Masatoshi; Kobayashi, Shozo; Komoriya, Satoshi; Yoshino, Toshiharu; Kanno, Hideyuki [Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 16, p. 4587 - 4592]
[7]Trost, Barry M.; Richardson, Jeffery; Yong, Kelvin [Journal of the American Chemical Society, 2006, vol. 128, # 8, p. 2540 - 2541]
[8]Motohashi, Shigeyasu; Satomi, Masakichi; Fujimoto, Yasuo; Tatsuno, Takashi [Heterocycles, 1985, vol. 23, # 8, p. 2035 - 2039]
[9]Grewe et al. [Chemische Berichte, 1956, vol. 89, p. 1978,1986]
[10]Goldsmith, David J.; John, T.K.; Middlesworth, Frank Van [Synthetic Communications, 1980, vol. 10, # 7, p. 551 - 558]
[11]Barral, Karine; Halfon, Philippe; Pèpe, Gérard; Camplo, Michel [Tetrahedron Letters, 2002, vol. 43, # 1, p. 81 - 84]
[12]Watson, Iain D. G.; Yudin, Andrei K. [Journal of the American Chemical Society, 2005, vol. 127, # 49, p. 17516 - 17529]
[13]Current Patent Assignee: BUCK INSTITUTE FOR RESEARCH ON AGING - WO2006/16167, 2006, A2 Location in patent: Page/Page column 62
[14]Current Patent Assignee: PFIZER INC - WO2008/75196, 2008, A1 Location in patent: Page/Page column 109-110
[15]Location in patent: experimental part Mayato, Carlos; Dorta, Rosa L.; Palazón, José M.; Vázquez, Jesús T. [Carbohydrate Research, 2012, vol. 352, p. 101 - 108]
[16]Misale, Antonio; Niyomchon, Supaporn; Luparia, Marco; Maulide, Nuno [Angewandte Chemie - International Edition, 2014, vol. 53, # 27, p. 7068 - 7073][Angew. Chem., 2014, vol. 126, # 27, p. 7188 - 7193,6]
[17]Current Patent Assignee: ISOMERASE THERAPEUTICS - WO2015/4455, 2015, A2 Location in patent: Page/Page column 23

5
[ 106-99-0 ]
[ 79-10-7 ]
[ 4771-80-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	In benzene at 120℃; for 2h;	1.i EXAMPLE 1 (i) 72 g (1 mol) of acrylic acid, 0.35 g of 4-t-butylcatechol and 288 g of benzene were added to a 1L-pressure reactor. After adding 70 g (1.3 mol) of 1,3-butadiene, the temperature was raised to 120° C. and, after 2 hours of reaction, the product was identified a 3-cyclohexene-1-carboxylic acid using 1H NMR spectrum and with a yield of more than 99% by gas chromatography. [0042] 1H NMR (CDCl3): δ1.70-1.82 (m, 1H), 1.94-2.35 (m, 5H), 2.49-2.75 (m, 1H), 5.59-5.79 (m, 2H) [0043] 3.2 g (2.5 wt. % of 3-cyclohexene-1-carboxylic acid) 3% Pd/C was added to the 3-cyclohexene-1-carboxylic acid solution and the reaction was activated at the temperature of 100° C. with a hydrogen pressure of 120 psi to yield cyclohexanecarboxylic acid with a conversion rate of more than 99%. [0044] 1H NMR (CDCl3): δ1.18-2.34 (m, 10OH), 2.35-2.40 (m, 1H)
99%	In hexane at 120℃; for 2h;	6 EXAMPLE 6 The procedures were performed in the same manner as described in Example 1, excepting that n-hexane was used as a solvent instead of benzene. [0059] More specifically, (i) 72 g (1.0 mol) of acrylic acid, 0.35 g of 4-t-butylcatechol and 288 g of n-hexane were added to a 1 L-pressure reactor. After adding 70 g (1.3 mol) of 1,3-butadiene, the temperature was raised to 120° C. and, after 2 hours of reaction, the product was identified as 3-cyclohexene-1-carboxylic acid with a yield of more than 99% by using GC.
99%	With tetraacetyl diborate In neat (no solvent) at -78 - 20℃;	3 General procedure: Generally, all reactions were performed with 5 mmol of acrylic acidand 5 mmol of isoprene with about 2 mol% of catalysts (about 10 mol% BOBPh4 wasused) in a 3 mL vial at ambient temperature, substantially in the absence of a solvent,except where a minimum amount of solvent was transferred into the reaction with thecatalyst (BCh was a 1 M solution in heptane and BH3 was a 1 M solution in THF).Exemplary experimental protocols for selected cycloaddition reactions are providedbelow. Similar protocols were carried out for the other cycloaddition reactions, and it willbe understood to those of ordinary skill in the art how to carry out such reactions.

With toluene at 125℃;

Reference： [1]Current Patent Assignee: KUMHO PETRO CHEMICAL CO.,LTD. - US2004/73068, 2004, A1 Location in patent: Page 3
[2]Current Patent Assignee: KUMHO PETRO CHEMICAL CO.,LTD. - US2004/73068, 2004, A1 Location in patent: Page 4
[3]Current Patent Assignee: MICHIGAN STATE UNIVERSITY - WO2017/53652, 2017, A1 Location in patent: Paragraph 00171; 00187
[4]Werber; Jansen; Gresham [Journal of the American Chemical Society, 1952, vol. 74, p. 532,534]
[5]Petrow; Ssopow [Zhurnal Obshchei Khimii, 1947, vol. 17, p. 2231][Chem.Abstr., 1948, p. 4957]

6
[ 100-50-5 ]
[ 4771-80-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	With C₄H₁₁FeMo₆NO₂₄^(3-)*3C₁₆H₃₆N⁽¹⁺⁾; water; oxygen; sodium carbonate at 50℃; for 8h; Green chemistry;
99%	With 4H₃N4H⁽¹⁺⁾CuMo₆O₁₈(OH)6^(4-); water; oxygen; sodium carbonate at 50℃; for 12h;
96%	With 2-mesityl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-2-ium tetrafluoroborate; 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine In acetonitrile at 20℃;

93%	With Oxone In N,N-dimethyl-formamide at 20℃; for 3h;
93%	With N-hydroxyphthalimide; oxygen In acetonitrile at 80℃; for 12h; Schlenk technique;
89%	With sodium hydroxide; silver(l) oxide In water for 1h;
75%	With silver(l) oxide In tetrahydrofuran; water for 4h; Ambient temperature;
	With dipyridinium dichromate In N,N-dimethyl-formamide
	With tert.-butylhydroperoxide In benzene at 60℃;
	With chromic acid
30 % Chromat.	With sodium chlorite; sodium dihydrogenphosphate; dimethyl sulfoxide In water Ambient temperature;
	With selenium(IV) oxide; dihydrogen peroxide

Reference： [1]Yu, Han; Ru, Shi; Dai, Guoyong; Zhai, Yongyan; Lin, Hualin; Han, Sheng; Wei, Yongge [Angewandte Chemie - International Edition, 2017, vol. 56, # 14, p. 3867 - 3871][Angew. Chem., 2017, vol. 129, # 14, p. 3925 - 3929,5]
[2]Yu, Han; Ru, Shi; Zhai, Yongyan; Dai, Guoyong; Han, Sheng; Wei, Yongge [ChemCatChem, 2018, vol. 10, # 6, p. 1253 - 1257]
[3]Zhao, Junfeng; Mueck-Lichtenfeld, Christian; Studer, Armido [Advanced Synthesis and Catalysis, 2013, vol. 355, # 6, p. 1098 - 1106]
[4]Travis, Benjamin R.; Sivakumar, Meenakshi; Hollist, G. Olatunji; Borhan, Babak [Organic Letters, 2003, vol. 5, # 7, p. 1031 - 1034]
[5]Dai, Peng-Fei; Qu, Jian-Ping; Kang, Yan-Biao [Organic Letters, 2019, vol. 21, # 5, p. 1393 - 1396]
[6]Lambert, Joseph B.; Marko, Dale E. [Journal of the American Chemical Society, 1985, vol. 107, # 26, p. 7978 - 7982]
[7]Loudon, G. Marc; Radhakrishna, A. S.; Almond, Merrick R.; Blodgett, James K.; Boutin, Raymond H. [Journal of Organic Chemistry, 1984, vol. 49, # 22, p. 4272 - 4276]
[8]Corey,E.J.; Schmidt,G. [Tetrahedron Letters, 1979, p. 399 - 402]
[9]Masuyama, Yoshiro; Takahashi, Masato; Kurusu, Yasuhiko [Tetrahedron Letters, 1984, vol. 25, # 39, p. 4417 - 4420]
[10]Gramenitskaya, V. N.; Inozemtseva, L. V.; Koz'mina, E. A.; Vul'fson, N. S. [Journal of Organic Chemistry USSR (English Translation), 1982, vol. 18, p. 2260 - 2267][Zhurnal Organicheskoi Khimii, 1982, vol. 18, # 12, p. 2561 - 2570]
[11]Dalcanale, Enrico; Montanari, Fernando [Journal of Organic Chemistry, 1986, vol. 51, # 4, p. 567 - 569]
[12]Current Patent Assignee: SHELL PLC - US2744929, 1952, A Current Patent Assignee: SHELL PLC - US2744928, 1952, A

7
[ 4771-80-6 ]
[ 5709-98-8 ]

Reference： [1]Journal of the American Chemical Society,1972,vol. 94,p. 3833 - 3844
[2]Helvetica Chimica Acta,2000,vol. 83,p. 1049 - 1078
[3]Organic Letters,1999,vol. 1,p. 1741 - 1744
[4]Patent: WO2011/146953,2011,A1
[5]Patent: EP2390245,2011,A1
[6]Patent: EP2399904,2011,A1
[7]Tetrahedron,2017,vol. 73,p. 1381 - 1388

8
[ 4771-80-6 ]
[ 923-42-2 ]

Reference： [1]Journal of Organic Chemistry,1961,vol. 26,p. 4303 - 4305

9
[ 4771-80-6 ]
[ 1679-51-2 ]

Yield	Reaction Conditions	Operation in experiment
100%	With lithium aluminium hydride In diethyl ether a) 22 deg C, 12 h, b) reflux, 4 h;
100%	With lithium aluminium hydride In tetrahydrofuran at 0 - 20℃; for 2h; Inert atmosphere;
71%	With C₂₅H₄₂N₆Rh⁽¹⁺⁾*CF₃O₃S^(1-); phenylsilane In tetrahydrofuran at 30℃; for 20h; Inert atmosphere;

63%	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With phenylsilane; potassium-t-butoxide; C₂₂H₃₀ClN₂RuS₂⁽¹⁺⁾*Cl^(1-) In tetrahydrofuran at 60℃; for 18h; Inert atmosphere; Stage #2: With water monomer; caesium fluoride In tert-butyl methyl ether at 20℃; for 3h; Inert atmosphere;	Cyclohex-3-enyl-methanol (2n): To a stirred suspension of 3-ene-cyclohexanoicacid (1n) (500 mg, 3.9635 mmol,1equiv.) in degassed solvent (10 V) was added ARP-03 (41.5 mg, 0.0792 mmol, 2mol%) and again degassed for 10 minutes. After 10 minutes of degassing, PhSiH3(1.47 mL, 11.8905 mmol, 3 equiv.) and t-BuOK (1 M in THF) (0.39 mL,0.3963 mmol, 10 mol%) were added dropwise to reaction mixture at RT. Thereaction mixture was heated to 60°C and stirred for 18 h. The reaction mixturewas then evaporated to remove volatiles, then suspended in MTBE and stirredwith aq. CsF solution (10%, 10 V) for 3 h. The organic layer was then separatedand concentrated in vacuum to furnish the crude, which was purified by columnchromatography on silica gel (eluent: Ethyl acetate / n-hexane = 0.5 / 4.5) toafford cyclohex-3-enyl-methanol (2n) (280mg, 63%) as a colourless oil.1H NMR (400 MHz, DMSO- d6): δ 5.70 - 5.50 (m, 2H), 4.42 (t, J = 5.2 Hz, 1H), 3.30 - 3.20 (m, 2H),2.05 - 1.90 (m, 3H), 1.80 - 1.50 (m,3H), 1.20 - 1.10 (m, 1H). 13C NMR (100 MHz, DEPT - 135, CDCl3): δ 127.26 (CH), 125.99 (CH),67.92 (CH2), 36.37 (CH), 28.18 (CH2), 25.30 (CH2),24.72 (CH2).LCMS (EI, m/z) calcd for C7H12O [M + Na]: 135.17 Found: 135.0
	With lithium aluminium hydride In diethyl ether for 5h; Heating;

Reference： [1]Yadav, Veejendra; Fallis, Alex G. [Canadian Journal of Chemistry, 1991, vol. 69, # 5, p. 779 - 789]
[2]Nagasawa, Shota; Sasano, Yusuke; Iwabuchi, Yoshiharu [Angewandte Chemie - International Edition, 2016, vol. 55, # 42, p. 13189 - 13194][Angew. Chem., 2016, vol. 128, p. 13383 - 13388,6]
[3]Nguyen, Thanh V. Q.; Yoo, Woo-Jin; Kobayashi, Shu [Advanced Synthesis and Catalysis, 2016, vol. 358, # 3, p. 452 - 458]
[4]Abhilash, Vishwanathan; Gadakh, Amol V.; Ganesh, Sambasivam; Hegde, Shivaprasad N.; Jacob, Anand; Karthik, C. S.; Lamees, Thundianandi; Mathivanan, Namachivayam; Sathiyanarayanan, Arumugam Murugan [Journal of Organometallic Chemistry, 2022, vol. 963]
[5]Perry,R.A. et al. [Canadian Journal of Chemistry, 1976, vol. 54, p. 2385 - 2401]

10
[ 4771-80-6 ]
[ 5708-19-0 ]

Reference： [1]Journal of the American Chemical Society,1972,vol. 94,p. 3833 - 3844
[2]Tetrahedron Asymmetry,2004,vol. 15,p. 2057 - 2060
[3]Patent: EP2368870,2011,A1
[4]Patent: EP2390245,2011,A1
[5]Patent: EP2399904,2011,A1
[6]Tetrahedron,2017,vol. 73,p. 1381 - 1388
[7]Patent: CN109942600,2019,A

11
[ 4771-80-6 ]
[ 64-17-5 ]
[ 15111-56-5 ]

Yield	Reaction Conditions	Operation in experiment
97.4%	With thionyl chloride at 0 - 5℃; for 4h; Reflux;	2 Example 2: Preparation of ethyl cyclohex-3-enecarboxylate (2-1) Add 600mL methanol and 252g cyclohex-3-enecarboxylic acid (1-1) to a 1000mL reaction flask,Stir to dissolve, control the temperature to 05, slowly add 360g thionyl chloride,After the addition, the temperature was raised to reflux, and the reaction was carried out for 4 hours.TLC tracked the end of the reaction, concentrated to remove the solvent, the obtained residue was dissolved in 400 mL of ethyl acetate, washed with 5% sodium bicarbonate solution, dried and concentrated,300 g of ethyl cyclohex-3-enecarboxylate (2-1) were obtained, yield: 97.4%.
	1.)thionyl chloride 2.)pyridine; Multistep reaction;

Reference： [1]Current Patent Assignee: WIND FIRE WHEEL SHANGHAI BIOTECHNOLOGY LTD - CN114181077, 2022, A Location in patent: Paragraph 0065-0069
[2]Setser, D. W.; Nguyen, Hanh H.; Danen, Wayne C. [Journal of Physical Chemistry, 1983, vol. 87, # 3, p. 408 - 417]

12
[ 4771-80-6 ]
[ 1666-13-3 ]
[ 116733-40-5 ]

Yield	Reaction Conditions	Operation in experiment
89%	With iodine pentoxide In acetonitrile at 20℃; for 0.166667h;
78%	With ammonium bromide In methanol at 15 - 20℃; for 0.416667h; electrolysis: (graphite/copper), constant current 400 mA;

Reference： [1]Zhou, Chen-Fan; Zhang, Yun-Qian; Ling, Yong; Ming, Liang; Xi, Xia; Liu, Gong-Qing; Zhang, Yanan [Organic and Biomolecular Chemistry, 2022, vol. 20, # 2, p. 420 - 426]
[2]Vukicevic; Konstantinovic; Mihailovic [Tetrahedron, 1991, vol. 47, # 4-5, p. 859 - 865]

13
[ 4771-80-6 ]
[ 930-65-4 ]

Yield	Reaction Conditions	Operation in experiment
35%	With lead(IV) acetate; lithium chloride In benzene for 7h; Heating;
	Multi-step reaction with 3 steps 1: SOCl₂ / benzene 2: pentane 3: PhCCl₃

Reference： [1]Lambert, Joseph B.; Marko, Dale E. [Journal of the American Chemical Society, 1985, vol. 107, # 26, p. 7978 - 7982]
[2]Slaugh,L.H. [Journal of the American Chemical Society, 1965, vol. 87, p. 1522 - 1526]

14
[ 4771-80-6 ]
[ 4103-88-2 ]

Yield	Reaction Conditions	Operation in experiment
78.5%	With sodium azide; chloroformic acid ethyl ester; triethylamine
	Multi-step reaction with 2 steps 1: (PhO)2PON₃; Et₃N / toluene / 0.5 h / 0 °C 2: toluene / 1 h / Heating
	With diphenyl phosphoryl azide; triethylamine In toluene at 20 - 80℃; for 4.5h;

	With diphenyl phosphoryl azide; triethylamine In toluene at 20 - 50℃; for 1.33333h; Reflux;	20.A Step A: fe -Butyl cyclohex-3 -enyl- l(i?)-carbamate and fe -Butyl cyclohex-3 -enyl- HS)- carbamate50:0 g of 3-cyclohexene-l-carboxylic acid and 500 ml of toluene were charged to a 2 L flask at 20-25 °C, the mixture obtained was stirred and 60.7 ml of triethylamine was added dropwise over 15 min followed by dropwise addition of 89.7 ml of DPP A over 20 min (gas evolution, exotherm to ~50 °C). To the mixture obtained 50 ml of toluene was added as a line rinse. The mixture obtained was heated to reflux and stirred until the reaction was complete determined by TLC and NMR. The reaction was shown to be complete after 1 h. The mixture obtained was cooled to 80 °C and 186 ml of t-BuOH was added dropwise over 10 min, followed by 1.26 g of CuCl and the mixture obtained was heated to reflux. The reaction was followed by NMR, and was shown to be complete after 1 h. The mixture obtained was cooled to 20 to 25 °C and 250 ml of saturated NaHC03 solution was added over 5 to 10 min. The mixture obtained was stirred for 30 min, filtered to remove residual solid and the solid was rinsed with 25 ml of toluene. The layers were separated and the aqueous layer was extracted with 2 x 150 ml of toluene. The organic layers were combined, washed with 150 ml of water and concentrated in vacuo. 79.8 g of a mixture of tert-butyl cyclohex-3 -enyl- 1 (i?)-carbamate and rt-butyl cy clohex-3 -enyl- 1 (5)-carbamate was obtained in the form of a brown solid.Optical Rotation: [a]D (CHC13) = 0°Purification by Column Chromatography:The crude mixture of tert-butyl cyclohex-3 -enyl- 1 (7?)-carbamate and tert-butyl cyclohex-3 - enyl-l(S)-carbamate was subjected to purification by column chromatography (eluent:cyclohexane/EtOAc 9:1). The required clean fractions were identified and combined. Concentration under vacuum gave the required product. 60.88 g of a mixture of tert-Butyl cyclohex-3-enyl-l(/?)- carbamate with tert-Butyl cyclohex-3-enyl-l(S)-carbamate was obtained in the form of a white solid.Optical Rotation: [a]D (CHCI3) = 0° NMR (200 MHz, CDC13, ppm) δ 5.69 - 5.53 (m, 2H), 4.55 (s, broad, 1H), 3.76 (s, broad, 1H), 2.41 - 2.30 (m, 1H), 2.12 - 2.08 (m, 2H), 1.91 - 1.76 (m, 2H), 1.6 - 1.48 (m, 1H), 1.43 (s, 9H)
	With diphenyl phosphoryl azide; triethylamine In toluene at 95℃; Inert atmosphere;
	With diphenyl phosphoryl azide; triethylamine In benzene at 20℃; for 24h; Inert atmosphere;

Reference： [1]Frater, G.; Mueller, U.; Schoepfer, U. [Tetrahedron Letters, 1984, vol. 25, # 3, p. 281 - 284]
[2]Donohoe, Timothy J.; Mitchell, Lee; Waring, Michael J.; Helliwell, Madeleine; Bell, Andrew; Newcombe, Nicholas J. [Organic and Biomolecular Chemistry, 2003, vol. 1, # 12, p. 2173 - 2186]
[3]Location in patent: experimental part Marco-Contelles, Jose; Gomez-Sanchez, Elena; Samadi, Abdelouahid; Soriano, Elena; Valderas, Carolina; Alvarez-Perez, Monica; Do Carmo Carreiras, Mria [ARKIVOC, 2010, vol. 2010, # 3, p. 56 - 73]
[4]Current Patent Assignee: NABRIVA THERAPEUTICS AG - WO2011/146954, 2011, A1 Location in patent: Page/Page column 57-58
[5]Walker, P. Ross; Campbell, Craig D.; Suleman, Abid; Carr, Greg; Anderson, Edward A. [Angewandte Chemie - International Edition, 2013, vol. 52, # 35, p. 9139 - 9143][Angew. Chem., 2013, vol. 125, # 36, p. 9309 - 9313]
[6]Kocak, Ramazan; Dastan, Arif; Saracoglu, Nurullah [Journal of Heterocyclic Chemistry, 2018, vol. 55, # 6, p. 1489 - 1493]

15
[ 4771-80-6 ]
[ 4720-83-6 ]
[ 63838-51-7 ]

Yield	Reaction Conditions	Operation in experiment
	With oxygen; sodium acetate In dimethyl sulfoxide at 80℃; for 36h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

Reference： [1]Larock, Richard C.; Hightower, Timothy R. [Journal of Organic Chemistry, 1993, vol. 58, # 20, p. 5298 - 5300]

16
[ 4771-80-6 ]
[ 98-89-5 ]

Yield	Reaction Conditions	Operation in experiment
99%	With hydrogen In benzene at 100℃;	1 EXAMPLE 1 3.2 g (2.5 wt. % of 3-cyclohexene-1-carboxylic acid) 3% Pd/C was added to the 3-cyclohexene-1-carboxylic acid solution and the reaction was activated at the temperature of 100° C. with a hydrogen pressure of 120 psi to yield cyclohexanecarboxylic acid with a conversion rate of more than 99%. [0044] 1H NMR (CDCl3): δ1.18-2.34 (m, 10OH), 2.35-2.40 (m, 1H)
99%	With hydrogen In hexane at 100℃;	6 EXAMPLE 6 3.2 g (2.5 wt. % of 3-cyclohexene-1-carboxylic acid) 3% Pd/C was added to the 3-cyclohexene-1-carboxylic acid solution and the reaction was activated at the temperature of 100 C. with a hydrogen pressure of 120 psi to yield cyclohexanecarboxylic acid with a conversion rate of more than 99%.
95%	With hydrogen In water for 18h; Ambient temperature;

Reference： [1]Current Patent Assignee: KUMHO PETRO CHEMICAL CO.,LTD. - US2004/73068, 2004, A1 Location in patent: Page 3
[2]Current Patent Assignee: KUMHO PETRO CHEMICAL CO.,LTD. - US2004/73068, 2004, A1 Location in patent: Page 4
[3]Larpent, Chantal; Dabard, Renee; Patin, Henri [Tetrahedron Letters, 1987, vol. 28, # 22, p. 2507 - 2510]

17
[ 1679-51-2 ]
[ 4771-80-6 ]

Yield	Reaction Conditions	Operation in experiment
83%	With chromium(VI) oxide; sulfuric acid In acetone at 0℃; Inert atmosphere;
81%	With Iron(III) nitrate nonahydrate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium chloride; oxygen In 1,2-dichloro-ethane at 25℃; for 48h;
81%	With Iron(III) nitrate nonahydrate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium chloride; oxygen In 1,2-dichloro-ethane at 20℃; for 48h; Schlenk technique;	15 Example 15: Synthesis of cyclohex-3-ene-1-carboxylic acid Other operations Reference Example 1 was carried out using cyclohexane-3-ene-1-methanol (114.7 mg, 98% purity,1.0 mmol) for 48 hours to give cyclohex-3-ene-1-carboxylic acid 102.5 mg, 81%) (petroleum ether: ethyl acetate= 5: 1).In the oxygen atmosphere (oxygen balloon)Fe (NO3) 3 · 9H2O (40.4 mg, 0.10 mmol),2,2,6,6-tetramethylpiperidine nitrogen oxide (TEMPO, 15.5 mg, 0.10 mmol)KCl (7.5 mg, 0.10 mmol),Dodecanol (189.0 mg, 98% purity, 1.0 mmol) and1,2-dichloroethane (DCE, 4 mL)Was added to a 50 mL Schlenk tube.Stir at room temperature for 12 h, TLC monitoring until completion of the reaction.The reaction solution was filtered through a short column of silica gel, eluted with ether (75 mL) and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5: 1)The corresponding dodecanoic acid (199.2 mg, 100%) was obtained.

78%	With manganese(II) bromide; silver carbonate; potassium hydroxide In 1,3,5-trimethyl-benzene at 50 - 165℃; for 20h; Schlenk technique; Inert atmosphere;
68%	With ruthenium trichloride; potassium hydroxide; potassium peroxomonosulphate for 6h; Ambient temperature;

Reference： [1]Walker, P. Ross; Campbell, Craig D.; Suleman, Abid; Carr, Greg; Anderson, Edward A. [Angewandte Chemie - International Edition, 2013, vol. 52, # 35, p. 9139 - 9143][Angew. Chem., 2013, vol. 125, # 36, p. 9309 - 9313]
[2]Jiang, Xingguo; Zhang, Jiasheng; Ma, Shengming [Journal of the American Chemical Society, 2016, vol. 138, # 27, p. 8344 - 8347]
[3]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES - CN107176899, 2017, A Location in patent: Paragraph 0051; 0052; 0053; 0054; 0094; 0095; 0096
[4]Ghalehshahi, Hajar Golshadi; Madsen, Robert [Chemistry - A European Journal, 2017, vol. 23, # 49, p. 11920 - 11926]
[5]Green, Graham; Griffith, William P.; Hollinshead, David M.; Ley, Steven V.; Schroeder, Martin [Journal of the Chemical Society. Perkin transactions I, 1984, # 4, p. 681 - 686]

18
[ 112391-51-2 ]
[ 4771-80-6 ]

Yield	Reaction Conditions	Operation in experiment
87%	In benzene at 20℃; for 1h;

Reference： [1]Fu, Gregory C.; Nguyen, SonBinh T.; Grubbs, Robert H. [Journal of the American Chemical Society, 1993, vol. 115, # 21, p. 9856 - 9857]

19
[ 4771-80-6 ]
3,4-Dihydroxycyclohexanecarboxylic acid-γ-lactone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With 5,10,15,20-tetra(2',6'-dichlorophenyl)porphyrinatoiron(III) chloride; iodosylbenzene In dichloromethane for 20h; Ambient temperature;
50%	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With 3-chloro-benzenecarboperoxoic acid In tetrachloromethane for 4h; Stage #2: With triethylamine In tetrachloromethane at 65℃; for 4h;	D1-1 Synthesis of D1-1 Procedure: m-CPBA was added to a solution of cyclohex-3-enecarboxylic acid in CCI4 and the reaction mixture was stirred for 4 h. Triethyl amine was added and the resulting reaction mixture was stirred at 65 °C for 4 h. Work up: The reaction mixture was concentrated under reduced pressure to get crude residue. Purification: The crude product was purified by flash column chromatography using ethyl acetate and petroleum ether as eluents. TLC system: 50% Ethyl acetate in pet ether, Rf value: 0.3 Nature of the compound: Light brown color solid, Yield: 50%
	Multi-step reaction with 2 steps 1: m-CPBA / CH₂Cl₂ / 0 °C 2: chlorobenzene / 130 °C

	Multi-step reaction with 2 steps 1: aqueous peroxyformic acid 2: 0.06 Torr
	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With 3-chloro-benzenecarboperoxoic acid Stage #2: With triethylamine	2.A Example 2 -Array feed of starter acids to S. hyciroscopicus MG7-9; Method A: Synthesis of (1/?, 3R, 4R)-3,4-dihydroxycyclohexanecarboxylic acid; (1R, 3R, 4R)-3,4-Dihydroxycyclohexanecarboxylic acid was readily attainable fromcommercially available racemic 3-cyclohexene carboxylic acid. This acid was epoxidisedthrough treatment with mefa-chloroperbenzoic acid and converted to the (1R, 3R, 4R*)-4-hydroxycyclohexane-1,3-carbolactone in situ by the addition of base (triethylamine), thus settingup the relative stereochemistries. This lactone was then hydrolysed by the action of aqueouspotassium hydroxide, and the final product purified over ion exchange resin (Corey, E. J. andHuang, H. 1989).

Reference： [1]Komuro, Masakatsu; Higuchi, Tsunehiko; Hirobe, Masaaki [Journal of the Chemical Society. Perkin transactions I, 1996, # 18, p. 2309 - 2313]
[2]Current Patent Assignee: ISOMERASE THERAPEUTICS - WO2015/4455, 2015, A2 Location in patent: Page/Page column 35
[3]Jones; Reamer; Desmond; Mills [Journal of the American Chemical Society, 1990, vol. 112, # 8, p. 2998 - 3017]
[4]Grewe et al. [Chemische Berichte, 1956, vol. 89, p. 1978,1986]
[5]Current Patent Assignee: BUCK INSTITUTE FOR RESEARCH ON AGING - WO2006/16167, 2006, A2 Location in patent: Page/Page column 62

20
(+-)-5c-cyano-2t-methoxy-cyclohexyl-r-mercury⁽¹⁺⁾ chloride [ No CAS ]
[ 4771-80-6 ]
[ 73873-61-7 ]

Reference： [1]Journal of the Chemical Society,1959,p. 227,233

21
[ 372-19-0 ]
[ 4771-80-6 ]
[ 263723-89-3 ]

Yield	Reaction Conditions	Operation in experiment
95%	With dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane
	With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide

Reference： [1]Nicolaou; Baran; Zhong; Sugita [Journal of the American Chemical Society, 2002, vol. 124, # 10, p. 2212 - 2220]
[2]Nicolaou; Zhong, Yong-Li; Baran, Phil S. [Angewandte Chemie - International Edition, 2000, vol. 39, # 3, p. 622 - 625]

22
[ 4771-80-6 ]
(1R*,3S*,4S*)-3,4-dibromocyclohexanecarboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With bromine In chloroform at 20℃; for 0.25h;
80%	With Oxalyl bromide; dimethyl sulfoxide In dichloromethane at -10 - 20℃; Inert atmosphere; stereoselective reaction;	Bromination of Alkenoic Acids Using DMSO and (COBr)₂; GeneralProcedure General procedure: To a solution of (COBr)2 (1.07 mL, 7.5 mmol, 1.5 equiv) in CH2Cl2 (10mL) at -10 °C was added dropwise a solution of DMSO (0.53 mL, 7.5mmol, 1.5 equiv) in CH2Cl2 (10 mL) under an atmosphere of nitrogen. After 10 min, a solution of alkenoic acid 1 (5 mmol, 1.0 equiv) in CH2Cl2 (10 mL) was added. The mixture was then allowed to warm to room temperature and stirred for 1 h. Distilled H2O (30 mL) was addeddropwise at 0 °C. After stirring for 10 min, the organic layer was separated and washed with brine (2 × 30 mL), dried (Na2SO4), filtered, and concentrated under vacuum. Purification by flash chromatography (silica gel, PE/EtOAc, 10:1) afforded the corresponding bromolactones 2a,d,g. The vicinal dibromo acids 3b,c,e,f,h-j can be obtained in high purity through simple pH adjustment as described above.
74%	With hydrogen bromide; dimethyl sulfoxide In chloroform; water at 65℃; for 12h;

Reference： [1]Krajewski, Krzysztof; Ciunik, Zbigniew; Siemion, Ignacy Z. [Tetrahedron Asymmetry, 2001, vol. 12, # 3, p. 455 - 462]
[2]Ding, Rui; Li, Jiaqi; Jiao, Wenyi; Han, Mengru; Liu, Yongguo; Tian, Hongyu; Sun, Baoguo [Synthesis, 2018, vol. 50, # 21, p. 4325 - 4335]
[3]Karki, Megha; Magolan, Jakob [Journal of Organic Chemistry, 2015, vol. 80, # 7, p. 3701 - 3707]

23
[ 4771-80-6 ]
[ 100-51-6 ]
[ 210574-45-1 ]

Yield	Reaction Conditions	Operation in experiment
81%	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With diphenylphosphoranyl azide; triethylamine In toluene at 25 - 110℃; for 4h; Inert atmosphere; Stage #2: benzyl alcohol In toluene at 110℃; for 12h;	33.1 Step 1: To a solution of cyclohex-3-enecarboxylic acid (20.0 g, 158.5 mmol) in toluene (360.0 mL) was added TEA (17.6 g, 174.3 mmol, 24.2 mL) and DPPA (45.8 g, 166.4 mmol, 36.0 mL). The mixture was degassed and purged with N2 for 3 times, it was stirred at 25°C for 1.5 h under N2 atmosphere. Then it was warmed to 1 10°C and stirred for another 2.5 h. BnOH (18.8 g, 174.3 mmol, 18.1 mL) was added to the mixture and the resulting mixture was stirred at 110°C for 12 h. The reaction was concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography to afford benzyl cyclohex-3-en-l-ylcarbamate (33.0 g, 81.0% yield) as a white solid. MR (400MHz, CHLOROF ORM-d) δ 7.44 - 7.29 (m, 5H), 5.73 - 5.65 (m, 1H), 5.63 - 5.56 (m, 1H), 5.1 1 (s, 2H), 4.81 (br s, 1H), 3.88 (br s, 1H), 2.41 (br d, J= 17.2 Hz, 1H), 2.19 - 2.09 (m, 2H), 1.96 - 1.84 (m, 2H), 1.66 - 1.52 (m, 1H).
81%	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With diphenyl phosphoryl azide; triethylamine In toluene at 25 - 110℃; for 4h; Inert atmosphere; Stage #2: benzyl alcohol In toluene at 110℃; for 12h;	33.1 Step 1 To a solution of cyclohex-3-enecarboxylic acid (20.0 g, 158.5 mmol) in toluene (360.0 mL) was added TEA (17.6 g, 174.3 mmol, 24.2 mL) and DPPA (45.8 g, 166.4 mmol, 36.0 mL). The mixture was degassed and purged with N2 for 3 times, it was stirred at 25°C for 1.5 h under N2 atmosphere. Then it was warmed to 110°C and stirred for another 2.5 h. BnOH (18.8 g, 174.3 mmol, 18.1 mL) was added to the mixture and the resulting mixture was stirred at 110°C for 12 h. The reaction was concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography to afford benzyl cyclohex-3-en-1-ylcarbamate (33.0 g, 81.0% yield) as a white solid.1H NMR (400MHz, CHLOROFORM-d) d 7.44 - 7.29 (m, 5H), 5.73 - 5.65 (m, 1H), 5.63 - 5.56 (m, 1H), 5.11 (s, 2H), 4.81 (br s, 1H), 3.88 (br s, 1H), 2.41 (br d, J = 17.2 Hz, 1H), 2.19 - 2.09 (m, 2H), 1.96 - 1.84 (m, 2H), 1.66 - 1.52 (m, 1H).
81%	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With diphenyl phosphoryl azide; triethylamine In toluene at 25 - 110℃; for 4h; Inert atmosphere; Stage #2: benzyl alcohol In toluene at 110℃; for 12h;	I.33.1 Step 1: To a solution of cyclohex-3-enecarboxylic acid (20.0 g, 158.5 mmol) in toluene (360.0 mL) was added TEA (17.6 g, 174.3 mmol, 24.2 mL) and DPPA (45.8 g, 166.4 mmol, 36.0 mL). The mixture was degassed and purged with N2 for 3 times, it was stirred at 25°C for 1.5 h under N2 atmosphere. Then it was warmed to 110°C and stirred for another 2.5 h. BnOH (18.8 g, 174.3 mmol, 18.1 mL) was added to the mixture and the resulting mixture was stirred at 110°C for 12 h. The reaction was concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography to afford benzyl cyclohex-3-en-1-ylcarbamate (33.0 g, 81.0% yield) as a white solid.1H NMR (400MHz, CHLOROFORM-d) d 7.44 - 7.29 (m, 5H), 5.73 - 5.65 (m, 1H), 5.63 - 5.56 (m, 1H), 5.11 (s, 2H), 4.81 (br s, 1H), 3.88 (br s, 1H), 2.41 (br d, J = 17.2 Hz, 1H), 2.19 - 2.09 (m, 2H), 1.96 - 1.84 (m, 2H), 1.66 - 1.52 (m, 1H).

80%	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With triethylamine In toluene at 20℃; for 0.5h; Inert atmosphere; Stage #2: With diphenylphosphoranyl azide In toluene at 110℃; for 4.5h; Stage #3: benzyl alcohol In toluene at 110℃; for 12h;	1 Dissolve 10g racemic 3-cyclohexenecarboxylic acid in 100ml toluene,Add 8.9g triethylamine dropwise under nitrogen protection,Then stir at room temperature for 30 minutes,Then slowly add 23.1g of diphenyl azide phosphate,After adding, continue to stir for 1.5 hours.Warm up to 110°C,Incubate and react for 3 hours.Drop 9.5g of benzyl alcohol,The reaction was continued for 12 hours at 110°C.Cool to room temperature,Add 100ml of saturated aqueous sodium bicarbonate solution,Separate the organic layer,After the aqueous phase was extracted with ethyl acetate, the organic phases were combined,Wash with saturated brine,Dry with anhydrous sodium sulfate,Concentrate under reduced pressure to obtain a crude product,The crude product was recrystallized from ethyl acetate/n-hexane to obtain benzyl cyclohexenyl carbamate 2a,White solid 14.5 g (80%).
74%	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With diphenylphosphoranyl azide; triethylamine In toluene for 0.5h; Heating; Stage #2: benzyl alcohol In toluene for 13h; Heating;
74%	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With diphenyl phosphoryl azide; triethylamine In toluene at 20 - 90℃; for 3h; Stage #2: benzyl alcohol In toluene at 90℃;	Synthesis of N-Protected Cycloalkeneamines; General Procedure General procedure: To a solution of cycloalkencarboxylic acid (12 mmol) in anhydrous toluene (30 mL), Et3N (12 mmol) and diphenylphosphoryl azide (DPPA, 12 mmol) were added and the resulting mixture was stirred for 2 h at r.t. and then for 1 h at 90 °C. A solution of benzyl alcohol (13.8 mmol) was added to this solution and the mixture was stirred overnight at 90 °C. The mixture was then diluted with EtOAc (40 mL) and washed with NaHCO3 (2 × 20 mL). The organic layer was dried over Na2SO4 and concentrated under vacuo. The crude material was purified by column chromatography on silica gel (n-hexane/EtOAc).
44%	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With diphenylphosphoranyl azide; triethylamine In toluene at 25 - 110℃; for 4h; Inert atmosphere; Large scale; Stage #2: benzyl alcohol In toluene at 110℃; for 8h; Large scale;	9 Example 9: Benzyl cyclohex-3-en- 1-ylcarbamate To a solution of cyclohex-3-enecarboxylic acid (17.5 kg, 138.9 mol, 1.00 equiv) in toluene (305 L) was added TEA (15.4 kg, 152.5 mol, 1.10 equiv), Diphenylphosphorylazide (DPPA) (40.1 kg, 145.8 mol, 1.05 equiv). The reaction was purged with an inert atmosphere of nitrogen. The mixture was stirred at 25 °C for 1.5 hours. Then the resulting solution was heated for an additional 2.5 hours while the temperature was maintained at 110°C. The phenylmethanol (16.5 kg, 152.8 mol, 1.10 equiv) was added dropwise into the above solution. The resulting solution was stirred for 8 hours at 110 °C. The reactionprogress was monitored by TLC (EA:PE=1:4) until the starting material was consumedcompletely. The resulting mixture was concentrated under vacuum. The residue was diluted with 500 L of DCM and then washed with 2x100 L of 10% 2-hydroxypropane- 1,2,3-tricarboxylic acid and 2x50 L of saturate sodium bicarbonate and lxlOO L of H20. The organic layer was dried over anhydrous sodium sulfate and concentrated undervacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (0-10%) to give 14 kg (purity=97%, yield=44%) of benzyl cyclohex-3- enylcarbamate as a white solid.

Reference： [1]Current Patent Assignee: CORNELL UNIVERSITY - WO2019/94641, 2019, A1 Location in patent: Paragraph 00369
[2]Current Patent Assignee: CORNELL UNIVERSITY - WO2020/232403, 2020, A1 Location in patent: Paragraph 00309
[3]Current Patent Assignee: CORNELL UNIVERSITY - WO2020/232401, 2020, A1 Location in patent: Paragraph 00333
[4]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES - CN111825563, 2020, A Location in patent: Paragraph 0008; 0019-0020
[5]Gómez-Sánchez, Elena; Marco-Contelles, José [Tetrahedron, 2005, vol. 61, # 5, p. 1207 - 1219]
[6]Ábrahámi, Renáta A.; Kiss, Loránd; Fustero, Santos; Fülöp, Ferenc [Synthesis, 2017, vol. 49, # 6, p. 1206 - 1213]
[7]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2017/29602, 2017, A2 Location in patent: Page/Page column 88; 89; 90

24
[ 4771-80-6 ]
C₇H₉IO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With iodine; sodium hydrogencarbonate; potassium iodide Inert atmosphere;
	With iodine; sodium hydrogencarbonate; potassium iodide In water at 0℃; for 0.0833333h;	1; 1.A To a solution of sodium bicarbonate (2Og) in water (325 ml) is added 3-cyclohexene-i-carboxylic acid (10g) at 0° C with stirring. To this solution is added an aqueous solution (200ml) of potassium iodide (79g) and iodine (21 g) with stirring. After stirring the dark solution for 5 min., chloroform (330 ml) is added and transferred to a separatory funnel. Organic layer is collected and the aqueous layer is extracted (2x300ml) with chloroform. Combined organic layer is washed with saturated solution of sodium thiosulfate (2x200ml), dried (anhydrous sodium sulfate), filtered, and concentrated to dryness to give compound Il (12g).

Reference： [1]Xie, Changmin; Luo, Jisheng; Zhang, Yuping; Huang, Sha-Hua; Zhu, Lili; Hong, Ran [Organic Letters, 2018, vol. 20, # 8, p. 2386 - 2390]
[2]Current Patent Assignee: GLYCOMIMETICS, INC. - WO2008/2449, 2008, A2 Location in patent: Page/Page column 11; 1/3

25
[ 4771-80-6 ]
[ 107-19-7 ]
prop-2'-yn-1'-yl N-(cyclohex-3-enyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With diphenyl-phosphinic acid; triethylamine In toluene at 80℃; for 5h; Stage #2: propargyl alcohol With copper(l) chloride In toluene for 4h; Heating; Further stages.;

Reference： [1]Gomez-Sanchez, Elena; Soriano, Elena; Marco-Contelles, Jose [Journal of Organic Chemistry, 2007, vol. 72, # 23, p. 8656 - 8670]

26
[ 67-56-1 ]
[ 4771-80-6 ]
[ 147330-12-9 ]

Yield	Reaction Conditions	Operation in experiment
76%	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With diphenyl-phosphinic acid; triethylamine In toluene for 4h; Heating; Stage #2: methanol With copper(l) chloride In toluene at 70℃; for 4h; Further stages.;

Reference： [1]Gomez-Sanchez, Elena; Soriano, Elena; Marco-Contelles, Jose [Journal of Organic Chemistry, 2007, vol. 72, # 23, p. 8656 - 8670]

27
[ 4771-80-6 ]
[ 4720-83-6 ]

Reference： [1]Journal of the American Chemical Society,2006,vol. 128,p. 2540 - 2541
[2]Journal of the American Chemical Society,2005,vol. 127,p. 17516 - 17529
[3]Bioorganic and Medicinal Chemistry,2005,vol. 13,p. 3964 - 3976
[4]Journal of Medicinal Chemistry,2005,vol. 48,p. 450 - 456
[5]Tetrahedron Asymmetry,2004,vol. 15,p. 581 - 584
[6]Tetrahedron Letters,2002,vol. 43,p. 81 - 84
[7]Tetrahedron,1981,vol. 37,p. 4097 - 4109
[8]Patent: WO2013/96926,2013,A1
[9]Patent: WO2014/70991,2014,A2
[10]Patent: WO2015/48616,2015,A1
[11]Patent: WO2017/191297,2017,A1

28
[ 4771-80-6 ]
cis-methyl 5-hydroxycyclohex-3-enecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 80 percent / KI; I₂; NaHCO₃ / H₂O 2: 92 percent / DBU / tetrahydrofuran / Heating 3: 94 percent / NaHCO₃ / 10 h / 20 °C
	Multi-step reaction with 3 steps 1: aq. NaHCO₃; NaI; I₂ / 20 °C 2: 4.78 g / 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 4 h / Heating 3: K₂CO₃ / 0.25 h / 20 °C
	Multi-step reaction with 3 steps 1: 93 percent / NaHCO₃; KI; I₂ / H₂O / 20 °C 2: 94 percent / DBU / tetrahydrofuran / Heating 3: 93 percent / NaHCO₃ / Heating

	Multi-step reaction with 2 steps 1.1: iodine; sodium hydrogencarbonate; potassium iodide / water / 24 h / Darkness; Inert atmosphere 2.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 6 h / Inert atmosphere; Reflux 2.2: 0.5 h / Inert atmosphere
	Multi-step reaction with 3 steps 1: sodium hydrogencarbonate; potassium iodide; iodine / water / 12 h / 20 °C 2: 1,8-diazabicyclo[5.4.0]undec-7-ene / tetrahydrofuran / 6 h / 70 °C / Inert atmosphere 3: sodium hydrogencarbonate / 10 h / 20 °C / Inert atmosphere

Reference： [1]Trost, Barry M.; Richardson, Jeffery; Yong, Kelvin [Journal of the American Chemical Society, 2006, vol. 128, # 8, p. 2540 - 2541]
[2]Watson, Iain D. G.; Yudin, Andrei K. [Journal of the American Chemical Society, 2005, vol. 127, # 49, p. 17516 - 17529]
[3]Yu, Seok-Ho; Chung, Sung-Kee [Tetrahedron Asymmetry, 2004, vol. 15, # 4, p. 581 - 584]
[4]Mayato, Carlos; Dorta, Rosa L.; Palazón, José M.; Vázquez, Jesús T. [Carbohydrate Research, 2012, vol. 352, p. 101 - 108]
[5]Misale, Antonio; Niyomchon, Supaporn; Luparia, Marco; Maulide, Nuno [Angewandte Chemie - International Edition, 2014, vol. 53, # 27, p. 7068 - 7073][Angew. Chem., 2014, vol. 126, # 27, p. 7188 - 7193,6]

29
[ 4771-80-6 ]
[ 4720-83-6 ]

Yield	Reaction Conditions	Operation in experiment
96%	With iodine; sodium hydrogencarbonate; potassium iodide In water at 20℃;
	Multi-step reaction with 2 steps 1: 94 percent / NaHCO₃, I₂/KI / H₂O / 21 h / 21 °C 2: 89 percent / DBU / tetrahydrofuran / 16 h / Heating
	Multi-step reaction with 2 steps 1: sodium hydrogencarbonate; potassium iodide; iodine / water / 12 h / 20 °C 2: 1,8-diazabicyclo[5.4.0]undec-7-ene / tetrahydrofuran / 6 h / 70 °C / Inert atmosphere

	Multi-step reaction with 2 steps 1: iodine; potassium iodide 2: 1,8-diazabicyclo[5.4.0]undec-7-ene
	Multi-step reaction with 2 steps 1: iodine; potassium iodide; sodium hydrogencarbonate / Inert atmosphere 2: 1,8-diazabicyclo[5.4.0]undec-7-ene / Inert atmosphere
	Multi-step reaction with 2 steps 1: potassium iodide; iodine; sodium hydrogencarbonate / water / 24 h / 20 °C / Inert atmosphere 2: 1,8-diazabicyclo[5.4.0]undec-7-ene / tetrahydrofuran / 12 h / Reflux; Inert atmosphere

Reference： [1]Ueda, Kyosuke; Umihara, Hirotatsu; Yokoshima, Satoshi; Fukuyama, Tohru [Organic Letters, 2015, vol. 17, # 13, p. 3191 - 3193]
[2]Bartlett,P.A.; Mcquaid,L.A. [Journal of the American Chemical Society, 1984, vol. 106, p. 7854]
[3]Misale, Antonio; Niyomchon, Supaporn; Luparia, Marco; Maulide, Nuno [Angewandte Chemie - International Edition, 2014, vol. 53, # 27, p. 7068 - 7073][Angew. Chem., 2014, vol. 126, # 27, p. 7188 - 7193,6]
[4]Current Patent Assignee: ISOMERASE THERAPEUTICS - WO2015/4455, 2015, A2
[5]Xie, Changmin; Luo, Jisheng; Zhang, Yuping; Huang, Sha-Hua; Zhu, Lili; Hong, Ran [Organic Letters, 2018, vol. 20, # 8, p. 2386 - 2390]
[6]Trongsiriwat, Nisalak; Li, Minyan; Pascual-Escudero, Ana; Yucel, Baris; Walsh, Patrick J. [Advanced Synthesis and Catalysis, 2019, vol. 361, # 3, p. 502 - 509]

30
[ 4771-80-6 ]
[ 4350-83-8 ]

Yield	Reaction Conditions	Operation in experiment
60%	With calcium(II) bis(trifluoromethanesulfonyl)imide; tert-butylammonium hexafluorophosphate(V) at 60℃; for 16h; Sealed tube;
	Multi-step reaction with 2 steps 1: 90 percent / base / CH₂Cl₂ / -78 - 25 °C 2: 80 percent / H₂ / Raney-Ni / Ambient temperature
	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With iodine; sodium hydrogencarbonate; potassium iodide In dichloromethane; water at 20℃; for 12h; Stage #2: With 2,2'-azobis(isobutyronitrile); tris-(trimethylsilyl)silane In toluene at 80℃; for 12h;

Multi-step reaction with 2 steps 1.1: sodium hydrogencarbonate / water 1.2: Darkness 2.1: palladium 10% on activated carbon; hydrogen; triethylamine / ethyl acetate / 2585.81 Torr

Reference： [1]Qi, Chenxiao; Yang, Shengwen; Gandon, Vincent; Lebœuf, David [Organic Letters, 2019, vol. 21, # 18, p. 7405 - 7409]
[2]Nicolaou, K.C. [Tetrahedron, 1981, vol. 37, # 23, p. 4097 - 4109]
[3]Caporaso, Lucia; Cavallo, Luigi; Chen, Eugene Y.-X.; Falivene, Laura; Li, Zi-Chen; Shi, Changxia [Chem, 2021, vol. 7, # 3, p. 670 - 685]
[4]Cheng, Peter T. W.; Kaltenbach, Robert F.; Zhang, Hao; Shi, Jun; Tao, Shiwei; Li, Jun; Kennedy, Lawrence J.; Walker, Steven J.; Shi, Yan; Wang, Ying; Dhanusu, Suresh; Reddigunta, Ramesh; Kumaravel, Selvakumar; Jusuf, Sutjano; Smith, Daniel; Krishnananthan, Subramaniam; Li, Jianqing; Wang, Tao; Heiry, Rebekah; Sum, Chi Shing; Kalinowski, Stephen S.; Hung, Chen-Pin; Chu, Ching-Hsuen; Azzara, Anthony V.; Ziegler, Milinda; Burns, Lisa; Zinker, Bradley A.; Boehm, Stephanie; Taylor, Joseph; Sapuppo, Julia; Mosure, Kathy; Everlof, Gerry; Guarino, Victor; Zhang, Lisa; Yang, Yanou; Ruan, Qian; Xu, Carrie; Apedo, Atsu; Traeger, Sarah C.; Cvijic, Mary Ellen; Lentz, Kimberley A.; Tirucherai, Giridhar; Sivaraman, Lakshmi; Robl, Jeffrey; Ellsworth, Bruce A.; Rosen, Glenn; Gordon, David A.; Soars, Matthew G.; Gill, Michael; Murphy, Brian J. [Journal of Medicinal Chemistry, 2021, vol. 64, # 21, p. 15549 - 15581]

31
[ 4771-80-6 ]
[ 22615-33-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 87 percent / thionyl chloride / Ambient temperature
	Multi-step reaction with 3 steps 1: diphenyl phosphoryl azide; triethylamine / toluene / 95 °C / Inert atmosphere 2: copper(l) chloride / Inert atmosphere 3: hydrogenchloride / 1,4-dioxane / Inert atmosphere

Reference： [1]Legraverend; Boumchita; Bisagni [Journal of Heterocyclic Chemistry, 1990, vol. 27, # 6, p. 1801 - 1804]
[2]Walker, P. Ross; Campbell, Craig D.; Suleman, Abid; Carr, Greg; Anderson, Edward A. [Angewandte Chemie - International Edition, 2013, vol. 52, # 35, p. 9139 - 9143][Angew. Chem., 2013, vol. 125, # 36, p. 9309 - 9313]

32
[ 4771-80-6 ]
[ 100-39-0 ]
[ 91503-67-2 ]

Yield	Reaction Conditions	Operation in experiment
83%	With triethylamine In N,N-dimethyl-formamide at 20℃; for 12h;
	With triethylamine In water; N,N-dimethyl-formamide	R.169 Benzyl (+-)-3-cyclohexene-1-carboxylate: [Referential Example 169] Benzyl (+-)-3-cyclohexene-1-carboxylate: (+-)-3-Cyclohexene-1-carboxylic acid (50 g) was dissolved in N,N-dimethylformamide (550 ml), and triethylamine (170 ml) and benzyl bromide (61 ml) were added under ice cooling to stir the mixture at room temperature for 12 hours. Water was added, extraction was conducted with ethyl acetate, and the resultant organic layer as washed with saturated saline and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane:ethyl acetate = 3:1) to obtain the title compound (70.8 g) as a reddish brown oil. 1H-NMR (CDCl3) δ: 1.66-1.76(1H,m), 2.00-2.13(3H,m), 2.27-2.29(2H,m), 2.58-2.65(1H,m), 5.13(2H,s), 5.66(2H,br.s), 7.29-7.38(5H,m).
	With sodium chloride; triethylamine In water; N,N-dimethyl-formamide	R.99 Benzyl 3-cyclohexene-1-carboxylate: REFERENTIAL EXAMPLE 99 Benzyl 3-cyclohexene-1-carboxylate: (+-)-3-Cyclohexene-1-carboxylic acid (50 g) was dissolved in N,N-dimethylformamide (550 ml), and triethylamine (170 ml) and benzyl bromide (61 ml) were added under ice cooling to stir the mixture at room temperature for 12 hours. Water was added, extraction was conducted with ethyl acetate, and the resultant organic layer was washed with saturated aqueous solution of sodium chloride and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane:ethyl acetate=3:1) to obtain the title compound (70.8 g). 1H-NMR (CDCl3) δ: 1.66-1.76(1H,m), 2.00-2.13(3H,m), 2.27-2.29(2H,m), 2.58-2.65(1H,m), 5.13(2H,s), 5.66(2H,br.s), 7.29-7.38(5H,m).

With triethylamine at 0 - 20℃; for 12h;

99 benzyl 3-cyclohexene-1-carboxylate: [Referential Example 99] benzyl 3-cyclohexene-1-carboxylate: (+-)-3-Cyclohexene-1-carboxylic acid (50 g) was dissolved in N,N-dimethylformamide (550 ml), and triethylamine (170 ml) and benzyl bromide (61 ml) were added under ice cooling to stir the mixture at room temperature for 12 hours.. water was added, extraction was conducted with ethyl acetate, and the resultant organic layer was washed with saturated aqueous solution of sodium chloride and then dried over anhydrous magnesium sulfate.. The solvent was distilled off under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane:ethyl acetate = 3:1) to obtain the title compound (70.8 g).1H-NMR (CDCl3) δ: 1.66-1.76(1H,m), 2.00-2.13(3H,m), 2.27-2.29(2H,m), 2.58-2.65(1H,m), 5.13(2H,s), 5.66(2H,br.s), 7.29-7.38(5H,m).

Reference： [1]Location in patent: scheme or table Nagata, Tsutomu; Nagamochi, Masatoshi; Kobayashi, Shozo; Komoriya, Satoshi; Yoshino, Toshiharu; Kanno, Hideyuki [Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 16, p. 4587 - 4592]
[2]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1270557, 2003, A1
[3]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US2005/20645, 2005, A1
[4]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1405852, 2004, A1 Location in patent: Page 107

33
[ 4771-80-6 ]
[ 75-65-0 ]
[ 135262-85-0 ]

Yield	Reaction Conditions	Operation in experiment
	With diphenyl phosphoryl azide; triethylamine at 20 - 90℃; for 49h;	138 3-Cyclohexene-1-carboxylic acid (25.3 g) was dissolved in tert-butanol (250 mL), and to the solution were added triethylamine (28 mL) and diphenylphosphoryl azide (43.0 mL), followed by stirring at room temperature for 1 hour, and then at 90°C for 2 days. The solvent was distilled away under reduced pressure, and the residue was purified by silica gel column chromatography (methylene chloride). The purified product was further purified by silica gel column chromatography (hexane : ethyl acetate = 20:1) to thereby give the title compound (24.9 g).1H-NMR(CDCl3) δ:1.45(9H, s), 1.45-1.60(1H, m), 1.80-1.90(2H, m), 2.05-2.20(2H, m), 2.35-2.45(1H, m), 3.78(1H, br), 4.56(1H, br), 5.55-5.65(1H, m), 5.65-5.75(1H, m).
	With diphenylphosphoranyl azide; triethylamine at 20 - 90℃; for 49h;	138 tert-Butyl 3-cyclohexen-1-ylcarbamate: [Referential Example 138] tert-Butyl 3-cyclohexen-1-ylcarbamate: 3-Cyclohexene-1-carboxylic acid (25.3 g) was dissolved in tert-butanol (250 ml), triethylamine (28 ml) and diphenylphosphorylazide (43.0 ml) were added, and the mixture was stirred for 1 hour at room temperature and 2 days at 90°C. The solvent was distilled off under reduced pressure, and the residue was purified by column chromatography on silica gel (methylene chloride) and then repurified by column chromatography on silica gel (hexane:ethyl acetate = 20:1) to obtain the title compound (24.9 g).1H-NMR (CDCl3) δ: 1.45(9H,s), 1.45-1.60(1H,m), 1.80-1.90(2H,m), 2.05-2.20(2H,m), 2.35-2.45(1H,m), 3.78(1H,br), 4.56(1H,br), 5.55-5.65(1H,m), 5.65-5.75(1H,m).
	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With triethylamine In toluene at 20℃; for 0.666667h; Inert atmosphere; Stage #2: With diphenylphosphoranyl azide In toluene at 110℃; for 5h; Stage #3: <i>tert</i>-butyl alcohol In toluene at 110℃; for 24h;	2 Dissolve 20g racemic 3-cyclohexenecarboxylic acid in 150ml toluene,17.8 g of triethylamine was added dropwise under the protection of nitrogen,Then stir at room temperature for 40 minutes,Then slowly add 46.2g of diphenyl azide phosphate,After adding, continue to stir for 2 hours.Warm up to 110°C,Incubate and react for 3 hours.Add 13g tert-butanol,The reaction was continued at 100°C for 24 hours.Cool to room temperature,Add 100ml of saturated aqueous sodium bicarbonate solution,Separate the organic layer,After the aqueous phase was extracted with ethyl acetate, the organic phases were combined,Wash with saturated brine,Dry with anhydrous sodium sulfate,Concentrate under reduced pressure to obtain 23 g of crude product tert-butyl cyclohexenyl carbamate 2b.

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1577301, 2005, A1 Location in patent: Page/Page column 138
[2]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1405852, 2004, A1 Location in patent: Page 127
[3]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES - CN111825563, 2020, A Location in patent: Paragraph 0008; 0223-0024

34
[ 4771-80-6 ]
[ 76140-13-1 ]

Yield	Reaction Conditions	Operation in experiment
92%	With sodium hypochlorite; acetic acid; sodium iodide In water monomer; acetonitrile at 20℃; for 3h;	10 Example 10 (Method 1; Synthesis of 4-iodo-6-oxabicyclo [3.2.1] octane-7-one) A reflux condenser, a dropping funnel,In a glass container with an internal volume of 200 mL equipped with a thermometer and a stirring device,30 mL of water, 13.66 g (91.2 mmol) of sodium iodide,Sodium hypochlorite solution (effective chlorine concentration 12%)57.78 g (95.1 mmol), and acetic acid 5.48 g (91.2 mmol)At an internal temperature of 20 ° CWhile maintaining it to be below.Then 3-cyclohexene-1-carboxylic acid10.0 g (79.3 mmol) and acetonitrile 10 mL were gently added and reacted at the same temperature for 3 hours with stirring.After completion of the reaction, 2.5 g (9.9 mmol) of sodium thiosulfate pentahydrate and 10 mL of water were added to the reaction solution, and after stirring at room temperature for 1 hour, the precipitated crystals were filtered. The obtained crystals were washed with 40 mL of water to obtain 18.43 g of 4-iodo-6-oxabicyclo [3.2.1] octane-7-one as yellowish white crystals (isolation yield: 92 %)
89%	With iodine; Sodium hydrogenocarbonate; sodium iodide In water monomer at 20℃;
84%	With iodine; Sodium hydrogenocarbonate; potassium iodide In water monomer at 20℃; for 18h;	1 4-lodo-6-oxabicyclo [3.2. 1] octan-7-one To a suspension of 3-cyclohexenecarboxylic acid (5.0 g, 40 mmol) in water (200 ml) was added, with vigorous stirring, sodium bicarbonate (9.90 g, 118 mmol). A solution of potassium iodide (39.0 g, 235 mmol) in water (125 ml) was prepared, and to this iodine (10 g, 40 mmol) was added to give a brown solution. This solution was added in one portion to the vigorously stirring solution of cyclohexenecarboxylate. The mixture was stirred at room temperature in the dark for 18 h. The resulting yellow solid was collected by filtration. The damp solid was dissolved in chloroform (150 ml) and washed with sodium thiosulfate solution (2 x 25 ml), and then with brine (25 ml). It was dried over magnesium sulfate, filtered and concentrated by rotary evaporation to afford iodolactone (8.5 g, 84%, m. p. 133- 134°C)

	With iodine; Sodium hydrogenocarbonate; potassium iodide In water monomer at 0 - 20℃; for 24h;
119 g	With iodine; Sodium hydrogenocarbonate; potassium iodide In water monomer at 0 - 20℃; Darkness;	1.2 Synthesis of compound 2 Compound 1 (60g) was suspended in H20 (800ml) and cooled to 0° C Solid NaHCQ3 (120g) was added in portion with stirring and then a solution of KI (474, 3g) and i2 (127g) in H20 (800ml) was added with stirring. Reaction mixture was stirred at room temperature overnight in the dark. Reaction mixture was extracted with CH2CI2 (3x500mi). Organic layer was washed with NaaSjOs solution (2x500ml) and then combined aqueous layer was extracted with CH2Ci2 (2X300ml). Organic layers (2100ml) were combined and washed with cold 0 (1x500ml) and cold brine (1x500ml), Organic layer was dried over Na2SC)4, filtered and concentrated to dryness to give compound 2 as light yellow crystals (119g). Purity: >95% by TLC.
119 g	With iodine; Sodium hydrogenocarbonate; potassium iodide In water monomer at 0 - 20℃; Darkness;	1.2 Synthesis of compound 2 Compound 1 (60 g) was suspended in HjO (800 mL) and cooled to 0 °C. Solid NaHC03 ( 120 g) was added in portion with stirring and then a solution of KI (474.3 g) and I2 ( 127 g) in H20 (800 mL) was added with stirring. Reaction mixture was stirred at room temperature overnight in the dark. Reaction mixture was then extracted with CH2CI2 (3 x500 mL). The organic layer was washed with Na2S2C>3 solution (2x500 mL) and then the combined aqueous layers were extracted with CH2CI2 (2x300 mL). Organic layers (2100 mL) were combined and washed with cold H2O ( 1 x500 mL) and cold brine ( 1 x 500 mL). The organic layer was dried over a2S0 , filtered, and concentrated to dryness to give compound 2 as l ight yellow crystals ( 1 19 g). Purity: >95% by TLC.
	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With Sodium hydrogenocarbonate In water monomer Stage #2: With iodine; potassium iodide In water monomer Darkness;
	With iodine; Sodium hydrogenocarbonate; potassium iodide In dichloromethane; water monomer at 20℃; for 12h;

Reference： [1]Current Patent Assignee: UBE INDUSTRIES LIMITED - JP2017/210468, 2017, A Location in patent: Paragraph 0032; 0033; 0034; 0035; 0036; 0039
[2]Muth, Felix; Günther, Marcel; Bauer, Silke M.; Döring, Eva; Fischer, Sabine; Maier, Julia; Drückes, Peter; Köppler, Jürgen; Trappe, Jörg; Rothbauer, Ulrich; Koch, Pierre; Laufer, Stefan A. [Journal of Medicinal Chemistry, 2015, vol. 58, # 1, p. 443 - 456]
[3]Current Patent Assignee: CATALYST BIOSCIENCES, INC. - WO2005/37832, 2005, A2 Location in patent: Page/Page column 67
[4]Weaver, Jimmie D.; Ka, Being J.; Morris, David K.; Thompson, Ward; Tunge, Jon A. [Journal of the American Chemical Society, 2010, vol. 132, # 35, p. 12179 - 12181]
[5]Current Patent Assignee: GLYCOMIMETICS, INC. - WO2014/70991, 2014, A2 Location in patent: Page/Page column 68
[6]Current Patent Assignee: GLYCOMIMETICS, INC. - WO2015/48616, 2015, A1 Location in patent: Paragraph 00127
[7]Cheng, Peter T. W.; Kaltenbach, Robert F.; Zhang, Hao; Shi, Jun; Tao, Shiwei; Li, Jun; Kennedy, Lawrence J.; Walker, Steven J.; Shi, Yan; Wang, Ying; Dhanusu, Suresh; Reddigunta, Ramesh; Kumaravel, Selvakumar; Jusuf, Sutjano; Smith, Daniel; Krishnananthan, Subramaniam; Li, Jianqing; Wang, Tao; Heiry, Rebekah; Sum, Chi Shing; Kalinowski, Stephen S.; Hung, Chen-Pin; Chu, Ching-Hsuen; Azzara, Anthony V.; Ziegler, Milinda; Burns, Lisa; Zinker, Bradley A.; Boehm, Stephanie; Taylor, Joseph; Sapuppo, Julia; Mosure, Kathy; Everlof, Gerry; Guarino, Victor; Zhang, Lisa; Yang, Yanou; Ruan, Qian; Xu, Carrie; Apedo, Atsu; Traeger, Sarah C.; Cvijic, Mary Ellen; Lentz, Kimberley A.; Tirucherai, Giridhar; Sivaraman, Lakshmi; Robl, Jeffrey; Ellsworth, Bruce A.; Rosen, Glenn; Gordon, David A.; Soars, Matthew G.; Gill, Michael; Murphy, Brian J. [Journal of Medicinal Chemistry, 2021, vol. 64, # 21, p. 15549 - 15581]
[8]Chen, Eugene Y.-X.; Clarke, Ryan W.; McGraw, Michael L.; Shi, Changxia [Journal of the American Chemical Society, 2022, vol. 144, # 5, p. 2264 - 2275]

35
[ 4771-80-6 ]
[ 100-39-0 ]
[ 480449-85-2 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In DMF (N,N-dimethyl-formamide) at 0 - 20℃; for 12h;	99 (+/-)-3-Cyclohexene-1-carboxylic acid (50 g) was dissolved in N,N-dimethylformamide (550 mL), and to the solution were added triethylamine (170 mL) and benzyl bromide (61 mL) under ice cooling, followed by stirring at room temperature for 12 hours. Water was added to the resultant mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and was dried over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure, and the residue was purified by silica gel column chromatography (hexane : ethyl acetate = 3:1), to thereby give the title compound (70.8 g).1H-NMR(CDCl3) δ:1.66-1.76(1H, m), 2.00-2.13(3H, m), 2.27-2.29(2H, m), 2.58-2.65(1H, m), 5.13(2H, s), 5.66(2H, br.s), 7.29-7.38(5H, m).

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1577301, 2005, A1 Location in patent: Page/Page column 117

36
[ 4771-80-6 ]
[ 210574-45-1 ]

Yield	Reaction Conditions	Operation in experiment
	With diphenylphosphoranyl azide; triethylamine; benzyl alcohol In benzene	33 PREPARATION 33 PREPARATION 33 A mixture of 3-cyclohexene-1-carboxylic acid (1.8 g), triethylamine (2.2 mL) and diphenylphosphoryl azide (3.93 g) in benzene (40 mL) was refluxed for 2 hours. After adding benzyl alcohol (1.54 g), the mixture was refluxed for 10 hours. The mixture was evaporated in vacuo and the obtained residue was diluted with ethyl acetate. The organic layer was washed successively with 1N hydrochloric acid, an aqueous saturated sodium hydrogen carbonate solution and brine. The obtained organic layer was dried over sodium sulfate and evaporated in vacuo. The residues was recrystallized from hexane-diethyl ether to give benzyl N-(3-cyclohexene-1-yl)carbamate (1.72 g) as a solid. NMR(CDCl3, δ): 1.58 (1H, m), 1.82-1.95 (2H, m), 2.05-2.36 (2H, m), 2.40 (1H, m), 3.88 (1H, m), 4.78 (1H, m), 5.55-5.72 (2H, m), 7.27-7.39 (5H, m).
	Multi-step reaction with 2 steps 1: diphenyl phosphoryl azide; triethylamine / benzene / 24 h / 20 °C / Inert atmosphere 2: benzene / 48 h / Reflux; Inert atmosphere

Reference： [1]Current Patent Assignee: ASTELLAS PHARMA INC. - US6582351, 2003, B1
[2]Kocak, Ramazan; Dastan, Arif; Saracoglu, Nurullah [Journal of Heterocyclic Chemistry, 2018, vol. 55, # 6, p. 1489 - 1493]

37
hydrous magnesium silicate [ No CAS ]
[ 169878-74-4 ]
[ 4771-80-6 ]
[ 932-67-2 ]
N-[4-[(6,11-Dihydro-5H-dibenz[b,e]azepin-5-yl)-carbonyl]phenyl]-3-cyclohexene-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; triethylamine In hexane; dichloromethane	255 N-[4-[(6,11-Dihydro-5H-dibenz[b,e]azepin-5-yl)-carbonyl]phenyl]-3-cyclohexene-1-carboxamide EXAMPLE 255 N-[4-[(6,11-Dihydro-5H-dibenz[b,e]azepin-5-yl)-carbonyl]phenyl]-3-cyclohexene-1-carboxamide A mixture of 208 mg of 3-cyclohexene-1-carbonyl chloride (prepared from 3-cyclohexene-1-carboxylic acid and thionyl chloride) and 145 mg of triethylamine in 3 ml of methylene chloride is added to a solution of 377 mg of 5-(4-aminobenzoyl)-6,11-dihydro-5H-dibenz[b,e]azepine in 7 ml of methylene chloride. The mixture is stirred for 18 hours, washed with water, 1N HCl, water, 1M NaHCO3 and brine then dried with Na2 SO4. The organic layer is passed through a short column of hydrous magnesium silicate and hexane added to the filtrate at the boil to give 340 mg of the desired product as a crystalline solid, m.p. 234°-236° C.
	With thionyl chloride; triethylamine In hexane; dichloromethane	255 N-[4-[(6,11-Dihydro-5H-dibenz[b,e]azepin-5-yl)carbonyl]phenyl]-3-cyclohexene-1-carboxamide EXAMPLE 255 N-[4-[(6,11-Dihydro-5H-dibenz[b,e]azepin-5-yl)carbonyl]phenyl]-3-cyclohexene-1-carboxamide A mixture of 208 mg of 3-cyclohexene-1-carbonyl chloride (prepared from 3-cyclohexene-1-carboxylic acid and thionyl chloride) and 145 mg of triethylamine in 3 ml of methylene chloride is added to a solution of 377 mg of 5-(4-aminobenzoyl)-6,11-dihydro-5H-dibenz[b,e]azepine in 7 ml of methylene chloride. The mixture is stirred for 18 hours, washed with water, 1N HCl, water, 1M NaHCO3 and brine then dried with Na2 SO4. The organic layer is passed through a short column of hydrous magnesium silicate and hexane added to the filtrate at the boil to give 340 mg of the desired product as a crystalline solid, m.p. 234°-236° C.
	With thionyl chloride; triethylamine In hexane; dichloromethane	255 N-[4-[(6,11-Dihydro-5H-dibenz[b,e]azepin-5-yl)carbonyl]phenyl]-3-cyclohexene-1-carboxamide Example 255 N-[4-[(6,11-Dihydro-5H-dibenz[b,e]azepin-5-yl)carbonyl]phenyl]-3-cyclohexene-1-carboxamide A mixture of 208 mg of 3-cyclohexene-1-carbonyl chloride (prepared from 3-cyclohexene-1-carboxylic acid and thionyl chloride) and 145 mg of triethylamine in 3 ml of methylene chloride is added to a solution of 377 mg of 5-(4-aminobenzoyl)-6,11-dihydro-5H-dibenz[b,e]azepine in 7 ml of methylene chloride. The mixture is stirred for 18 hours, washed with water, 1N HCl, water, 1M NaHCO3 and brine then dried with Na2 SO4. The organic layer is passed through a short column of hydrous magnesium silicate and hexane added to the filtrate at the boil to give 340 mg of the desired product as a crystalline solid, m.p. 234°-236° C.

Reference： [1]Current Patent Assignee: CARDIOKINE BIOPHARMA - US5686445, 1997, A
[2]Current Patent Assignee: CARDIOKINE BIOPHARMA - US5736538, 1998, A Current Patent Assignee: CARDIOKINE BIOPHARMA - US5739128, 1998, A Current Patent Assignee: CARDIOKINE BIOPHARMA - US5869483, 1999, A Current Patent Assignee: CARDIOKINE BIOPHARMA - US5747487, 1998, A Current Patent Assignee: CARDIOKINE BIOPHARMA - US5512563, 1996, A
[3]Current Patent Assignee: CARDIOKINE BIOPHARMA - US5693635, 1997, A Current Patent Assignee: CARDIOKINE BIOPHARMA - US5760031, 1998, A

38
tetrabutoxytitanium [ No CAS ]
[ 4771-80-6 ]
[ 2807-30-9 ]
[ 149574-00-5 ]

Yield	Reaction Conditions	Operation in experiment
75%	With phosphoric acid In water; toluene	18.40 Epoxidation and Other Derivatizations A 500 ml, round-bottom flask equipped with a 10-tray Oldershaw column and decanting head, thermometer, and a connecting tube with stopcock was charged with 126 grams (1.0 mole) of 3-cyclohexene-1-carboxylic acid, 99 grams (0.95 mole) of 2-propoxyethanol, and 100 ml of toluene. The reaction mass was stirred and brought to reflux. Then 1.1 grams of titanium tetrabutoxide was added via the connecting tube. The temperature of the reaction mass was slowly increased to 200° C. and held at this temperature while removing water and solvent overhead. After a reaction time of 8 hours, the product was cooled and washed with 50 ml of dilute phosphoric acid (10 weight percent in water) and filtered to remove the titanium salts. The organic layer was separated from the water layer, and the organic layer was successively washed with 50 ml portions of a saturated sodium bicarbonate solution and with water. Distillation of the crude product under vacuum through a 12-cm Vigreux column gave 152 grams (75% yield) of 2-propoxyethyl 3-cyclohexenecarboxylate (b.p. 88°-90° C. at 2.0 mm Hg) with a chromatographically analyzed purity exceeding 98%.

Reference： [1]Current Patent Assignee: DOW INC - US5268489, 1993, A

39
[ 6493-77-2 ]
3-cyclohexene-1-methyl 3-cyclohexene-1-carboxylate [ No CAS ]
[ 4771-80-6 ]
[ 72581-32-9 ]
[ 100-49-2 ]

Yield	Reaction Conditions	Operation in experiment
77%	With hydrogen; sodium methylate;C44H48Cl2N2P2Ru; In tetrahydrofuran; at 100℃; under 37503.8 Torr; for 2.5h;Autoclave;Product distribution / selectivity;	Under argon, a solution of methyl 3-cyclohexene-1-carboxylate (2.810 g, 20 mmol) in THF (2 mL) was added with a syringe, followed by more THF (2?1 mL), to a Keim autoclave equipped with a glass liner containing RuCl2(L-1) (8.4 mg, 0.01 mmol, 0.05 mol %), solid NaOMe (109.7 mg, 2.0 mmol, 10 mol %), and THF (10 mL). Then, the autoclave was pressurised with hydrogen gas at 50 bars and placed in a thermosttated oil bath set at 100 C. After 2,5 h, the autoclave was removed from the oil bath, and cooled in a cold-water bath. The glass liner was removed from the autoclave, and the reaction mixture was diluted with citric acid 10% w/w (25 mL) and extracted with MTBE (100 mL). Gas chromatography after silylation showed the following products: methyl 3-cyclohexene-1-carboxylate (2%), cyclohexanemethanol (2%), 3-cyclohexene- 1-methanol (91%), 3-cyclohexen-1-carboxylic acid (2%), 3-cyclohexene-1-methyl 3-cyclohexene-1-carboxylate (3%). Purification by flash chromatography on silica gel with pentane/Et2O (10/1?1/1) as elution mixture gave the desired 3-cyclohexene-1-methanol (1.768 g, 15.4 mmol, 77%) as a colorless liquid.1H NMR (CDCl3, 400 MHz): ? 5.68 (s, AB syst., 2H), 3.57-3.49 (m, AB syst, 2H), 2.2-2 (m, 3H), 1.9-1.7 (m, 4H), 1.35-1.2 (m, 1H).13C NMR (CDCL3, 100 MHz): ? 127.1 (CH), 125.9 (CH), 67.8 (CH2), 36.32 (CH), 28.1 (CH2), 25.2 (CH2), 24.6 (CH2).
67 - 77%	With hydrogen; sodium methylate;RuCl2(L-1); In tetrahydrofuran; at 80 - 100℃; under 37503.8 Torr; for 2.5 - 5h;Product distribution / selectivity;	Exemple 3Chemo selective Hydrogenation of Esters using with complexes of formula (1)Hydrogenation of methyl 3-cyclohexene-l-carboxylate was taken as model substrate using complexes RuCl2(L-I) and RuCl2(L-2). Structures of ligands are described in Table 1 and the results are summarised in Table 5. Typical reaction condition is described bellow for RuCl2(L-I): Under argon, a solution of methyl 3-cyclohexene-l-carboxylate (2.810 g, 20 mmol) in THF (2 mL) was added with a syringe, followed by more THF (2 x 1 mL), to a Keim autoclave equipped with a glass liner containing RuCl2(L-I) (8.4 mg, 0.01 mmol, 0.05 mol%), solid NaOMe (109.7 mg, 2.0 mmol, 10 mol%), and THF (10 mL). Then, the autoclave was pressurised with hydrogen gas at 50 bars and placed in a thermosttated oil bath set at 1000C. After 2 h 30 min, the autoclave was removed from the oil bath, and cooled in a cold-water bath. The glass liner was removed from the autoclave, and the reaction mixture was diluted with citric acid 10% w/w (25 mL) and extracted with MTBE (100 mL). Gas chromatography after silylation showed the following products: methyl 3-cyclohexene-l-carboxylate (2%), cyclohexanemethanol (2%), 3-cyclohexene-l- methanol (91%), 3-cyclohexen-l-carboxylic acid (2%), 3-cyclohexene-l -methyl EPO <DP n="20"/>3-cyclohexene-l-carboxylate (3%). Purification by flash chromatography on silica gel with pentane/Et2O (10/1 - > 1/1) as elution mixture gave the desired 3-cyclohexene-l- methanol (1.768 g, 15.4 mmol, 77%) as a colorless liquid. 1H NMR (CDCl3, 400 MHz): delta 5.68 (s, AB syst, 2H), 3.57-3.49 (m, AB syst, 2H), 2.2-2(m, 3H), 1.9-1.7 (m, 4H), 1.35-1.2 (m, IH). 13C NMR (CDCL3, 100 MHz): delta 127.1 (CH), 125.9 (CH), 67.8 (CH2), 36.32 (CH), 28.1(CH2), 25.2 (CH2), 24.6 (CH2).Table 5: Chemo selectivity observed with complexes of formula (1)Conv.: Conversion (in %, analysed by GC after silylation) of ester to alcohol after 2h30min.Reaction conditions: Substrate (20 mmol), H2 gas (50 bars), RuCl2(L-n) 0.05 mol%,NaOMe 10 mol%, THF (14 mL) at 1000C during 2h 30min.1} Reaction run at 8O0C during 5h.

Reference： [1]Patent: US2008/71098,2008,A1 .Location in patent: Page/Page column 9
[2]Patent: WO2006/106484,2006,A1 .Location in patent: Page/Page column 18-19

40
[ 4771-80-6 ]
oxo((5,10,15,20-tetrakis(2,6-dimethyl-3-sulfonatophenyl)porphinato)chromium(V))Na₄⁽¹⁺⁾ [ No CAS ]
[ 41088-52-2 ]
(((5,10,15,20-tetrakis(2,6-dimethyl-3-sulfonatophenyl)porphinato)chromium(III)dihydrate)Na₄)⁽¹⁺⁾ [ No CAS ]

Reference： [1]Inorganic Chemistry,1990,vol. 29,p. 2019 - 2021

41
[ 20816-12-0 ]
[ 4771-80-6 ]
[ 64-02-8 ]
Na₆H₄[Os(ethylenediaminetetraacetate)3] [ No CAS ]

Reference： [1]Inorganica Chimica Acta,1978,vol. 28,p. 69 - 72

42
[ 4771-80-6 ]
[ 593-56-6 ]
[ 53102-82-2 ]

Yield	Reaction Conditions	Operation in experiment
93%	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With triethylamine In dichloromethane for 0.0833333h; Inert atmosphere; Stage #2: N-methoxylamine hydrochloride With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 10h; Inert atmosphere;

Reference： [1]Wardrop, Duncan J.; Bowen, Edward G.; Forslund, Raymond E.; Sussman, Adam D.; Weerasekera, Samanthi L. [Journal of the American Chemical Society, 2010, vol. 132, p. 1188 - 1189]

43
[ 4771-80-6 ]
[ 74-88-4 ]
[ 16646-42-7 ]

Yield	Reaction Conditions	Operation in experiment
97%	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With n-butyllithium; bis(dimethylamino)(i-propyl)phosphine oxide; diisopropylamine In tetrahydrofuran; hexane at -20 - 20℃; Inert atmosphere; Stage #2: methyl iodide In tetrahydrofuran; hexane at -25 - 20℃;
	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With n-butyllithium; N-ethyl-N,N-diisopropylamine In tetrahydrofuran; hexane at -78 - 60℃; for 2.5h; Stage #2: methyl iodide In tetrahydrofuran; hexane at 20℃;	Formation of 1-methylcyclohex-3-ene-1-carboxylic acid (52a) Formation of 1-methylcyclohex-3-ene-1-carboxylic acid (52a) (2432) N-isopropylpropan-2-amine (50.1 g, 69.5 mL, 495.5 mmol) was dissolved in 50 mL of THF. To the solution was added n-butyllithium (174.4 mL of 2.5 M solution in hexanes, 436.0 mmol) at -78° C. The resulting solution was stirred for 30 minutes at -78° C. To the reaction was then added cyclohex-3-ene-1-carboxylic acid (25.0 g, 198.2 mmol) and the reaction was allowed to warm to 60° C. for 2 hrs. The reaction was cooled to room temp and iodomethane (29.5 g, 13.0 mL, 208.1 mmol) was added and the reaction was allowed to stir overnight and then quenched with 1 N HCl until the pH<4. The crude product was extracted into CH2Cl2 and water. The organic phase was concentrated in vacuo to a yellow oil (27 g) and used without further purification. (2433) MS/RT: 141.09 (M+H)/1.65
27 g	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With n-butyllithium; N-ethyl-N,N-diisopropylamine In tetrahydrofuran; hexane at -78 - 60℃; for 2h; Stage #2: methyl iodide In tetrahydrofuran; hexane	Formation of 1-methylcyclohex-3-ene-1-carboxylic acid (52a) N-isopropylpropan-2-amine (50.1 g, 69.5 mL, 495.5 mmol) was dissolved in 50 mL of THF. To the solution was added n-butyllithium (174.4 mL of 2.5 M solution in hexanes, 436.0 mmol) at -78° C. The resulting solution was stirred for 30 minutes at -78° C. To the reaction was then added cyclohex-3-ene-1-carboxylic acid (25.0 g, 198.2 mmol) and the reaction was allowed to warm to 60° C. for 2 hrs. The reaction was cooled to room temp and iodomethane (29.5 g, 13.0 mL, 208.1 mmol) was added and the reaction was allowed to stir overnight and then quenched with 1 N HCl until the pH2Cl2and water. The organic phase was concentrated in vacuo to a yellow oil (27 g) and used without further purification.

Reference： [1]Hosoya, Masahiro; Otani, Yuko; Kawahata, Masatoshi; Yamaguchi, Kentaro; Ohwada, Tomohiko [Journal of the American Chemical Society, 2010, vol. 132, # 42, p. 14780 - 14789]
[2]Current Patent Assignee: VERTEX PHARMACEUTICALS (OLD) - US9345708, 2016, B2 Location in patent: Page/Page column 389
[3]Current Patent Assignee: VERTEX PHARMACEUTICALS (OLD) - JP2015/38146, 2015, A Location in patent: Paragraph 1000

44
[ 5709-98-8 ]
[ 4771-80-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 20 - 120℃; for 18h;Product distribution / selectivity;	(R)-3-Cyclohexene-1-carboxylic acid (1.0 g, 97% ee) was dissolved in N,N-dimethylformamide (10 ml). To the solution, 60% sodium hydride (634 mg) was added at room temperature, and the mixture was stirred at 120C for 18 hours. The reaction solution was cooled to room temperature, and 10% aqueous citric acid solution was then added dropwise thereto, followed by extraction with cyclopentyl methyl ether. The organic layer was washed with water and then dried over anhydrous magnesium sulfate. The solvent was distilled off, and the obtained residue was then subjected to silica gel column chromatography (chloroform-methanol=3:1) to obtain 892 mg of the title compound as a colorless oil. Its optical purity was 0% ee. The H-NMR spectroscopic data were in agreement with those of Example 3.

Reference： [1]Patent: EP2368870,2011,A1 .Location in patent: Page/Page column 14
[2]Patent: EP2368870,2011,A1
[3]Patent: EP2368870,2011,A1

45
[ 4771-80-6 ]
[ 3886-69-9 ]
[ 1352834-09-3 ]

Yield	Reaction Conditions	Operation in experiment
66.9%	In acetone at 55 - 60℃; for 2.83333h; Reflux;	2.A 191.93 g of racemic cyclohex-3-ene-1-carboxylic acid were charged to a flask and 5 volumes of acetone were added. The mixture obtained was stirred, heated to 55 to 60°C and stirred for approximately 30 min. To the mixture obtained 1.0 equivalent of (R)-(+)-methylbenzylamine in 2 volumes of acetone were added dropwise over approximately 50 min. A clear, yellow solution was obtained and refluxed for 2 h. The solution obtained was cooled slowly to rt. Crystallisation started at approximately 50°C. Once at rt from the mixture obtained the precipitate was filtered off, washed with acetone and dried in vacuo at 40°C overnight. A methylbenzylamine salt of cyclohex-3-ene-l-carboxylic acid as set out in the reaction scheme above was obtained. Yield: 251.76 g (66.9% of theory); Optical Rotation: [α]D (c=5.12, MeOH) = -7.7°
66.9%	In acetone at 55 - 60℃; for 3.33333h; Reflux;	14.A A. Salt Formation 191.93 g of racemic cyclohex-3-ene-1-carboxylic acid were charged to a flask and 5 volumes of acetone were added. The mixture obtained was stirred, heated to 55 to 60°C and stirred for approximately 30 min. To the mixture obtained 1.0 equivalent of (R)-(+)-methylbenzylamine in 2 volumes of acetone were added dropwise over approximately 50 min. A clear, yellow solution was obtained and refluxed for 2 h. The solution obtained was cooled slowly to rt. Crystallisation started at approximately 50°C. Once at rt from the mixture obtained the precipitate obtained was filtered off, washed with acetone and dried in vacuo at 40°C overnight. A methylbenzylamine salt of cyclohex-3-ene-1-carboxylic acid as set out in the reaction scheme above was obtained. Yield: 251.76 g (66.9% of theory); Optical Rotation: [α]D (c=5.12, MeOH) = -7.7°

Reference： [1]Current Patent Assignee: NABRIVA THERAPEUTICS AG - EP2390245, 2011, A1 Location in patent: Page/Page column 14-15
[2]Current Patent Assignee: NABRIVA THERAPEUTICS AG - EP2399904, 2011, A1 Location in patent: Page/Page column 24-25

46
[ 4771-80-6 ]
[ 75-11-6 ]
[ 710314-32-2 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With diethylzinc In dichloromethane; toluene at 0℃; for 0.25h; Stage #2: diiodomethane In dichloromethane; toluene at 20℃;	A solution of cyclohex-3- enecarboxylic acid (1.8 g, 26 mmol) in dichloro methane (20 mL) was added to a 1.1 M solution of Et,Zn in toluene (26 mL, 28.5 mmol) at 0 °C and the resulting suspension was stirred for 15 min. Diiodomethane (2.9 mL, 25.6 mmol) in dichloromethane (3 mL) was then added dropwise and the pale yellow suspension was stirred at rt overnight as a white precipitate appeared. The reaction mixture was poured into IN HCl and extracted with diethyl ether (3 x 60 mL). The organic phase was extracted with IN KOH. The aqueous phase was then acidified with IN HCl and extracted with dichloromethane. Evaporation of the solvent gave the title compound as a white solid; only one diastereomer was detectable by 1H NMR. 1H NMR (400 MHz, CDC13) 5 2.34-2.26 (m, 1H), 2.21-2.13 (m, 1H), 1.98-1.94 (m, 1H), 1.84- 1.78 (m, 1H), 1.76-1.70 (m, 1H), 1.59-1.52 (m, 1H), 1.75-1.07 (m, 1H), 0.93-0.88 (m, 2H), 0.62-0.57 (m, 1H). MS m/z 141.2 (M + 1).

Reference： [1]Current Patent Assignee: Novartis (w/o Sandoz); NOVARTIS AG - WO2012/87519, 2012, A1 Location in patent: Page/Page column 102

47
[ 4771-80-6 ]
4-bromo-6-oxabicyclo[3.2.1]octan-7-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With 5,6-difluoro-2-(1-phenylethyl)benzo[d][1,2]selenazol-3(2H)-one; bromine; potassium carbonate In dichloromethane at 20℃; for 7h;

Reference： [1]Balkrishna, Shah Jaimin; Prasad, Ch Durga; Panini, Piyush; Chopra, Deepak; Kumar, Sangit; Detty, Michael R. [Journal of Organic Chemistry, 2012, vol. 77, # 21, p. 9541 - 9552,12]

48
[ 4771-80-6 ]
C₇H₉IO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
119 g	With iodine; sodium hydrogencarbonate; potassium iodide In water at 0 - 20℃; Darkness;	1 Synthesis of compound 2 Compound 1 (60 g) was suspended in H20 (800 ml) and cooled to 0°C. Solid NaHC03 (120 g) was added in portion with stirring and then a solution of KI (474.3 g) and I2 (127 g) in H20 (800 ml) was added with stirring. Reaction mixture was stirred at room temperature overnight in the dark. Reaction mixture was then extracted with CH2C12 (3 x500 ml). The organic layer was washed with Na2S203 solution (2x500 ml) and then the combined aqueous layers were extracted with CH2C12 (2x300 ml). Organic layers (2100 ml) were combined and washed with cold H20 (1x500 ml) and cold brine (1 x 500 ml). The organic layer was dried over Na2S04, filtered, and concentrated to dryness to give compound 2 as light yellow crystals (119 g). Purity: >95% by TLC.

Reference： [1]Current Patent Assignee: GLYCOMIMETICS, INC. - WO2013/96926, 2013, A1 Location in patent: Page/Page column 54

49
[ 4771-80-6 ]
[ 1538583-91-3 ]
[ 1538584-16-5 ]

Yield	Reaction Conditions	Operation in experiment
82%	With silver carbonate In acetonitrile at 80℃; for 8h; chemoselective reaction;

Reference： [1]Wei, Tao; Xie, Ming-Sheng; Qu, Gui-Rong; Niu, Hong-Ying; Guo, Hai-Ming [Organic Letters, 2014, vol. 16, # 3, p. 900 - 903]

50
[ 4771-80-6 ]
[ 62-53-3 ]
N-phenylcyclohex-3-ene-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 0.25h; Inert atmosphere; Stage #2: aniline In dichloromethane at 20℃; Inert atmosphere;
	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; for 1h; Inert atmosphere; Stage #2: aniline In tetrahydrofuran at 20℃; Inert atmosphere;	General Procedure I: General procedure: Under an inert atmosphere, CDI (1.0 equiv) was added to a solution of the corresponding carboxylic acid (1.0 equiv) in dry THF (1.0 M) (Caution CO 2 is released violently). Upon stirring at rt for 1 h, the corresponding aniline derivative (1.0 equiv) was added. The reaction was stirred at rt overnight. Then, it was taken to dryness under reduced pressure and purified using an automated system (silica gel, hexanes/EtOAc gradient), obtaining the corresponding products.

Reference： [1]Iosub, Andrei V.; Stahl, Shannon S. [Journal of the American Chemical Society, 2015, vol. 137, # 10, p. 3454 - 3457]
[2]Zheng, Shuai; Gutiérrez-Bonet, Álvaro; Molander, Gary A. [Chem, 2019, vol. 5, # 2, p. 339 - 352]

51
[ 4771-80-6 ]
[ 6638-79-5 ]
[ 113489-32-0 ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 0.25h; Inert atmosphere; Stage #2: N,O-dimethylhydroxylamine*hydrochloride In dichloromethane at 20℃; Inert atmosphere;
80%	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In tetrahydrofuran; ethyl acetate at 0 - 5℃; for 0.166667h; Inert atmosphere; Stage #2: N,O-dimethylhydroxylamine*hydrochloride In tetrahydrofuran; ethyl acetate at 0 - 25℃; for 1.83333h; Inert atmosphere;	General procedure for the synthesisof Weinreb amides (2a-r) General procedure: To a solution of acid 1 (1.0g, 8.9 mmol) in THF (15 mL) was added Et3N (3.1 mL, 22.2 mmol), and T3P (50% solution in EtOAc, 10.6mL, 17.7 mmol) at 0-5 °C and the solution was stirred for about 10 min under a nitrogen atmosphere. Then N,O-dimethylhydroxylaminehydrochloride salt (1.1g, 13.3 mmol) was added to the reaction mixture at 0-5 °C and the heterogeneous mixture was allowed to stir at room temperature till the completion of the reactionas indicated by TLC (see Table S-1). The mixture was then diluted with water(20 mL) followed by ethyl acetate (20 mL) and stirred for about 10 min. The separated organic layer was collected, washed with 5% citric acid (2 x10 mL),5% Na2CO3 (2 x 10 mL), and then brine solution. The collected organic layer was dried over anhydrous Na2SO4, filtered and concentrated under low vacuum. The crude product obtainedwas purified by flash column chromatography over silicagel (100-200 mesh) using 12-15% EtOAc / n-hexane as eluent to affordthe desired compound.

Reference： [1]Iosub, Andrei V.; Stahl, Shannon S. [Journal of the American Chemical Society, 2015, vol. 137, # 10, p. 3454 - 3457]
[2]Jammula, Subba Rao; Anna, Venkateswara Rao; Tatina, Sudhakar; Krishna, Thalishetti; Sreenivas, B. Yogi; Pal, Manojit [Tetrahedron Letters, 2016, vol. 57, # 35, p. 3924 - 3928]

52
[ 4771-80-6 ]
racemate-4-iodo-6-oxa-bicyclo[3.2.1]octan-7-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With iodine; sodium hydrogencarbonate; potassium iodide In dichloromethane; water at 5 - 20℃; for 3h;	1 Step 1: Synthesis of Racemate-4-iodo-6-oxa-bicyclo[3.2.1]octan-7-one To a mixture of cyclohex-3-enecarboxylic acid (racemate, 42.0 g, 333 mmol), potassium iodide (72.0 g, 433 mmol) and sodium hydrogencarbonate (36.4 g, 433 mmol) in methylene chloride (750 mL) and water (750 mL) was added iodine (110.0 g, 433 mmol) at an internal temperature of 5° C., and the reaction mixture was stirred at room temperature for 3 hours. After quenched with 1 N aqueous sodium thiosulfate (1500 mL), the resulting mixture was extracted with methylene chloride (1000 mL×2). The combined organic layers were washed with aqueous sodium hydrogencarbonate (1000 mL), water (2000 mL) and brine (1000 mL), dried over anhydrous magnesium sulfate, filtered, then concentrated under reduced pressure. The precipitated crystals were collected by filtration and washed with hexane, followed by drying, to thereby give the title compound (80.2 g, 95%) as a white solid.

Reference： [1]Current Patent Assignee: BLUEPRINT MEDICINES CORP - US2015/119405, 2015, A1 Location in patent: Paragraph 0306; 0307; 0308

53
[ 4771-80-6 ]
C₁₃H₁₈O₃ [ No CAS ]
C₂₀H₂₆O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
11.5 g	With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 16h; Inert atmosphere; Cooling;	3.1 Under a nitrogen atmosphere, 3-cyclohexene-1-carboxylic acid (5.0 g), compound [H6] ( 8.8 g), Do is allowed to cool to a mixture of DMAP (1.0g), dichloromethane (50ml) While DCC (8.9g), and the mixture was stirred at room temperature for 16 hours. The precipitated insoluble matter to vacuum filtration More removed and the organic layer was separated by adding water to the filtrate, and the obtained organic layer 2N hydrochloric acid and water sequentially Using washed following, and dried over anhydrous magnesium sulfate. The residue obtained by the solvent was evaporated under reduced pressure Column chromatography (silica gel, eluent: toluene - ethyl acetate mixture (volume ratio : Toluene / ethyl acetate = 8/1)) to give the colorless liquid [H8] (11.5 g) was obtained.

Reference： [1]Current Patent Assignee: CHISSO CORPORATION - JP5803076, 2015, B2 Location in patent: Paragraph 0180; 0181

54
[ 4771-80-6 ]
[ 87144-93-2 ]
C₂₂H₃₆O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
14.3 g	With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 16h; Inert atmosphere; Cooling;	4.1 Under a nitrogen atmosphere, 3-cyclohexene-1-carboxylic acid (10.0 g), 1-hydroxy - 4-propyl dicyclohexane (12.6g), DMAP (1.9g), dichloromethane While cooling the mixture of (100ml) DCC (17.2g), was added at room temperature for 16 hours And the mixture was stirred. The precipitated insoluble matter was removed by vacuum filtration, and the organic layer was separated by adding water to the filtrate, The resulting organic layer was washed sequentially with 2N hydrochloric acid and water, dried over anhydrous magnesium sulfate It was. The residue obtained by solvent was distilled off under reduced pressure column chromatography (silica gel, eluent : Purified by toluene), and recrystallization (toluene - methanol mixture (volume ratio: Torr En / methanol = 1/5)) to give the compound of colorless crystals [H9] (14.3 g) was obtained.

Reference： [1]Current Patent Assignee: CHISSO CORPORATION - JP5803076, 2015, B2 Location in patent: Paragraph 0184; 0185

55
[ 524-38-9 ]
[ 4771-80-6 ]
1,3-dioxoisoindolin-2-yl cyclohex-3-ene-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃;
88%	With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; Inert atmosphere; Schlenk technique;
73%	With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃;

68%	With dmap; diisopropyl-carbodiimide In dichloromethane Inert atmosphere; Schlenk technique;
	With dicyclohexyl-carbodiimide at 20℃;
	With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃; Schlenk technique; Inert atmosphere;
	With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 5 - 10h;	2.1 Preparation of redox active esters General procedure: The corresponding carboxylic acids (10 mmol, 1 equiv), N-hydroxyphthalimide (11 mmol, 1.1 equiv), and 4-dimethylaminopyridine (0.1 mmol, 10 mol%) were mixed in a flask with a magnetic stirring bar, 30 mL CH2Cl2 was added. Then a solution of N, N-dicyclohexylcarbodiimide (11 mmol, 1.1 equiv) in CH2Cl2 (10 mL) was added slowly at room temperature. The reaction mixture was maintained at room temperature with stirring for 5-10h. The white precipitate was filtered off and the solution was concentrated on a rotary evaporator. The residue was purified by flash column chromatography to give corresponding redox active esters.
	With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃;
	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃; for 0.0833333h; Stage #2: N-hydroxyphthalimide In dichloromethane at 20℃;
	With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; Inert atmosphere; Schlenk technique;
	With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃; for 5h;
	With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃;	General procedure for the synthesis of NHPI esters General procedure: A round-bottom flask was charged with N-hydroxyphthalimide (NHPI, 815 mg, 5.0 mmol, 1.0 equiv), carboxylic acid (5.0 mmol, 1.0 equiv, if solid), and DMAP (61 mg, 0.5 mmol, 0.1 equiv). Dry dichloromethane (25 mL, 0.2 M) was added, and the mixture was stirred vigorously. Carboxylic acid (1.0 equiv) was added via syringe (if liquid). DIC (780 µL, 5.0 mmol, 1.0 equiv) was added dropwise via syringe, and the mixture was allowed to stir until the carboxylic acid was consumed (determined by TLC). Typical reaction times were between 1 h and 12 h. The mixture was filtered over celite and rinsed with additional CH2Cl2. The solvent was removed under reduced pressure, and purification by column chromatography afforded corresponding activated esters 2 (NHPI esters). All of the NHPI esters have been previously reported.

Reference： [1]Zheng, Chao; Wang, Yuting; Xu, Yangrui; Chen, Zhen; Chen, Guangying; Liang, Steven H. [Organic Letters, 2018, vol. 20, # 16, p. 4824 - 4827]
[2]Lu, Xiao-Yu; Gao, Ang; Ge, Meng-Yuan; Xia, Ze-Jie; Liu, Qi-Le; Tao, Ting-Hua; Sun, Xiao-Mei [Journal of Organic Chemistry, 2022, vol. 87, # 7, p. 4654 - 4669]
[3]Zhang, Yu-Lan; Yang, Lei; Wu, Jie; Zhu, Chunyin; Wang, Peng [Organic Letters, 2020, vol. 22, # 19, p. 7768 - 7772]
[4]Liu, Lixin; Pan, Neng; Sheng, Wei; Su, Lebin; Liu, Long; Dong, Jianyu; Zhou, Yongbo; Yin, Shuang-Feng [Advanced Synthesis and Catalysis, 2019, vol. 361, # 17, p. 4126 - 4132]
[5]Lu, Xi; Xiao, Bin; Liu, Lei; Fu, Yao [Chemistry - A European Journal, 2016, vol. 22, # 32, p. 11161 - 11164]
[6]Xue, Weichao; Oestreich, Martin [Angewandte Chemie - International Edition, 2017, vol. 56, # 38, p. 11649 - 11652][Angew. Chem., 2017, vol. 129, p. 11808 - 11811,4]
[7]Lu, Xiao-Yu; Li, Jing-Song; Hong, Mei-Lan; Wang, Jin-Yu; Ma, Wen-Jing [Tetrahedron, 2018, vol. 74, # 49, p. 6979 - 6984]
[8]Lyu, Xue-Li; Huang, Shi-Sheng; Song, Hong-Jian; Liu, Yu-Xiu; Wang, Qing-Min [Organic Letters, 2019, vol. 21, # 14, p. 5728 - 5732]
[9]Liu, Yichang; Xue, Liwei; Shi, Biyin; Bu, Faxiang; Wang, Dan; Lu, Lijun; Shi, Renyi; Lei, Aiwen [Chemical Communications, 2019, vol. 55, # 99, p. 14922 - 14925]
[10]Cao, Tianpeng; Liao, Saihu; Nie, Xingliang; Xu, Ruting; Xu, Tianxiao; Yang, Mingcheng [Organic Letters, 2020, vol. 22, # 9, p. 3692 - 3696]
[11]Cai, Yi-Ping; Nie, Fang-Yuan; Song, Qin-Hua [Journal of Organic Chemistry, 2022, vol. 87, # 2, p. 1262 - 1271]
[12]Dong, Jianyu; Gan, Xinyang; Geng, Furong; Wu, Shaofeng; Zhou, Yongbo [Tetrahedron Letters, 2022, vol. 96]

56
[ 4771-80-6 ]
3,4-dihydroxycyclohexanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With 3-chloro-benzenecarboperoxoic acid In tetrachloromethane at 20℃; Stage #2: With triethylamine In tetrachloromethane for 4h; Reflux; Stage #3: With hydrogenchloride In tetrahydrofuran; water	2 Cyclohexene-3-carboxylic acid (15 g) was dissolved in carbon tetrachloride (100 mL)Then, 29 g of m-chloroperoxybenzoic acid was added, and the mixture was stirred overnight at room temperature.Was then added 45mL of triethylamine was heated at reflux for four hours,After the spin-dry the solvent through the column (PE: EA = 1: 1),To give the pure product 5g,5g of pure product by adding 25ml of tetrahydrofuran and then added20mL of 2N hydrochloric acid was stirred overnight.After recovering the solvent to give 3,4-dihydroxy cyclohexane acid 3g,Yield 25%.

Reference： [1]Current Patent Assignee: SHANGHAI OCEAN UNIVERSITY - CN105061424, 2016, B Location in patent: Paragraph 0039; 0041

57
[ 4771-80-6 ]
[ 100-46-9 ]
(+/-)-cyclohex-3-enecarboxylic acid benzylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With pentamethoxy tantalum; 1-(Trimethylsilyl)imidazole In neat (no solvent) at 50℃; for 48h; Inert atmosphere; Sealed tube;
	With benzotriazol-1-ol; 1,2-dichloro-ethane; triethylamine In N,N-dimethyl-formamide at 23℃; for 16h; Inert atmosphere;
65 %Spectr.	With phenylsilane; FeH₆Mo₆O₂₄^(3-)3H₃N7H₂O*3H⁽¹⁺⁾ In toluene at 120℃; for 36h; Schlenk technique; Inert atmosphere;

Reference： [1]Muramatsu, Wataru; Yamamoto, Hisashi [Journal of the American Chemical Society, 2019, vol. 141, # 48, p. 18926 - 18931]
[2]Hie, Liana; Baker, Emma L.; Anthony, Sarah M.; Desrosiers, Jean-Nicolas; Senanayake, Chris; Garg, Neil K. [Angewandte Chemie - International Edition, 2016, vol. 55, # 48, p. 15129 - 15132][Angew. Chem., 2016, vol. 128, # 48, p. 15353 - 15356]
[3]Shi, Da; Wang, Aiping; Wang, Jingjing; Xie, Ya; Yu, Han [Chemical Communications, 2022, vol. 58, # 8, p. 1127 - 1130]

58
[ 4771-80-6 ]
[ 112-60-7 ]
C₂₂H₃₄O₇ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	With toluene-4-sulfonic acid In toluene Dean-Stark; Large scale;	2 Following esterification, a standard procedure (Dean-Starks distillation in toluene) was used. Average batch size that may be prepared using this method was 1.0 to 1 .5 kg (2.4 to 3.7 mol) using 0.5 to 0.8 kg of TEG (average yield of 99 %)

Reference： [1]Current Patent Assignee: HENKEL AG & CO. KGAA - WO2016/119848, 2016, A1 Location in patent: Page/Page column 9; 10

59
[ 4771-80-6 ]
[ 365997-33-7 ]

Reference： [1]Tetrahedron,2017,vol. 73,p. 1381 - 1388
[2]Patent: CN112321613,2021,A

60
[ 4771-80-6 ]
[ 136030-00-7 ]
[ 5709-98-8 ]
(S)-3-cyclohexane-1-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In water; isopropyl alcohol; at 60℃;	Crude (S) -3-cyclohexane-1-carboxylic acid / (1R, 2S) -1-amino-3-cyclohexane-1-carboxylic acid (4.55 g), (1R, 2S) -1-amino-2-indanol (4.30 g) was added to water containing 2-propanol (45 mL), heated to 60 C. To dissolve the precipitate. The reaction solution was cooled to 50 C. and stirred for 2 hours after crystallization. It was gradually cooled to room temperature at 5 C / h and stirred for 12 hours. The precipitate was collected by filtration, washed with 2-propanol (10 mL), and dried under reduced pressure at 40 C. to obtain the title compound (5.05 g, 50.9%, 26.5% ee) as a white solid

Reference： [1]Patent: JP2016/65024,2016,A .Location in patent: Paragraph 0042

61
[ 4771-80-6 ]
[ 67-68-5 ]
[ 105679-09-2 ]

Yield	Reaction Conditions	Operation in experiment
78%	Stage #1: dimethyl sulfoxide With oxalyl dichloride In dichloromethane at 0℃; for 0.166667h; Stage #2: 1,2,5,6-tetrahydrobenzoic acid In dichloromethane at 20℃;	Methylthio-Substituted Lactones 2a-j; General Procedure General procedure: To a solution of DMSO (2.3 mL, 30 mmol, 3.0 equiv) in CH2Cl2 (30 mL) cooled at 0 °C was added dropwise a solution of oxalyl chloride (1.3 mL, 15 mmol, 1.5 equiv) in CH2Cl2 (20 mL). After 10 min, a solution of alkenoic acid (10 mmol, 1.0 equiv) in CH2Cl2 (20 mL) was added. The mixture was then allowed to warm up to r.t. and stirred overnight. Et3N (7.0 mL, 50 mmol, 5.0 equiv) was added in one portion. After stirring for 20 min, the mixture was diluted with CH2Cl2 (60 mL). The organic layer was successively washed with sat. aq NH4Cl solution (50 mL) and brine (2 × 50 mL). The combined organic extracts were dried (MgSO4), filtered, and concentrated under reduced pressure. Purification by flash chromatography (silica gel, petroleum ether/EtOAc 10:1) afforded the corresponding sulfenyl lactone. In an optimized procedure, CH2Cl2 was replaced by MeCN and the reaction mixture was heated to reflux after addition of substrate.

Reference： [1]Zhang, Ting; Dai, Yifeng; Cheng, Siwei; Liu, Yongguo; Yang, Shaoxiang; Sun, Baoguo; Tian, Hongyu [Synthesis, 2017, vol. 49, # 6, p. 1380 - 1386]

62
[ 75-91-2 ]
[ 4771-80-6 ]
[ 946-00-9 ]

Yield	Reaction Conditions	Operation in experiment
74%	Stage #1: tert.-butylhydroperoxide; 1,2,5,6-tetrahydrobenzoic acid With dmap In dichloromethane; water at 0℃; for 0.166667h; Inert atmosphere; Stage #2: With dicyclohexyl-carbodiimide In dichloromethane; water at 0 - 20℃; Inert atmosphere;
	Stage #1: tert.-butylhydroperoxide; 1,2,5,6-tetrahydrobenzoic acid With dmap In dichloromethane; water at -15℃; for 0.166667h; Inert atmosphere; Stage #2: With dicyclohexyl-carbodiimide In dichloromethane; water at -15 - 10℃; for 1.5h; Inert atmosphere;
	Stage #1: tert.-butylhydroperoxide; 1,2,5,6-tetrahydrobenzoic acid With dmap; dihydrogen peroxide In dichloromethane; water at 0℃; for 0.166667h; Inert atmosphere; Green chemistry; Stage #2: With dicyclohexyl-carbodiimide In dichloromethane; water at 0 - 20℃; for 2h; Inert atmosphere; Green chemistry;

With dmap; dicyclohexyl-carbodiimide In dichloromethane; water for 1.5h; Inert atmosphere; Cooling;

Reference： [1]Ge, Liang; Jian, Wujun; Zhou, Huan; Chen, Shaowei; Ye, Changqing; Yu, Fei; Qian, Bo; Li, Yajun; Bao, Hongli [Chemistry - An Asian Journal, 2018, vol. 13, # 17, p. 2522 - 2528]
[2]Zhu, Xiaotao; Ye, Changqing; Li, Yajun; Bao, Hongli [Chemistry - A European Journal, 2017, vol. 23, # 43, p. 10254 - 10258]
[3]Babu, Kaki Raveendra; Zhu, Nengbo; Bao, Hongli [Organic Letters, 2017, vol. 19, # 1, p. 46 - 49]
[4]Ye, Changqing; Qian, Bo; Li, Yajun; Su, Min; Li, Daliang; Bao, Hongli [Organic Letters, 2018, vol. 20, # 11, p. 3202 - 3205]

63
[ 4771-80-6 ]
4-azatetracyclo[5.3.2.0^2,6.0^8,10]dodec-11-ene hydrochloride [ No CAS ]
cyclohex-3-en-1-yl((4R,4aR,5aS,6S,6aS)-3,3a,4,4a,5,5a,6,6a-octahydro-4,6-ethenocyclopropa[f]isoindol-2(1H)-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
199 mg	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In ethyl acetate at 20℃;	10 Example 10: cyclohex-3-en- 1 -yl((4R,4aR,5aS,6S,6aS)-3 ,3a,4,4a,5 ,5a,6,6a-octahydro-4,6-ethenocyclopropa[f]isoindol-2( 1 H)-yl)methanone To a solution of 4-azapentacyclo[5.3.2.02’6.08’10]dodec-11-ene hydrochloride (200 mg,1.03 mmol) in EtOAc (10 mL) were added 3-cyclohexene carboxylic acid (119 mg,0.94 mmol), HOBt (190mg, 1.41 mmol), EDC (218 mg, 1.41 mmol) and triethylamine(0.6 mL, 4.14 mmol). The reaction mixture was stirred at room temperature overnight.To the resulting suspension was then added water (10 mL) and the phases wereseparated. The organic phase was washed with saturated aqueous NaHCO3 solution (10 mL) and brine (10 mL), dried over anh. Na2SO4 and filtered. Evaporation in vacuo of the organics gave the title compound as a yellowish solid (259 mg, quantitative yield). Column chromatography (Hexane/Ethyl acetate mixture) gave the compound as a whitesolid (199 mg), m. p. 78-79 °C. JR (ATR) v: 682, 710, 763, 816, 839, 854, 887, 915,940, 981, 1016, 1034, 1087, 1135, 1168, 1203, 1221, 1274, 1292, 1332, 1355, 1380,1431, 1620, 1651, 2870, 2926, 3022 cm1. Elemental analysis: Calculated forC18H23N0: C 80.26%, H 8.61%, N 5.20%. Found: C 80.24%, H 8.73%, N 5.19%.

Reference： [1]Current Patent Assignee: UNIVERSITAT DE BARCELONA; CIDQO 2012 S L - WO2017/182464, 2017, A1 Location in patent: Page/Page column 38; 39

64
[ 4771-80-6 ]
(4S)-4-iodo-6-oxabicyclo[3.2.1]octan-7-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With sodium hydrogencarbonate In water at 20℃; Stage #2: With iodine; potassium iodide In water at 20℃; Darkness;	10.1 Example 10: General procedure for the preparation of modified alkyl chain acyclic purine nucleoside analogues Step 1: To a stirred solution of sodium hydrogencarbonate (7.50 g, 90 mmol, 3 equiv.) in water (73 mL), was added 3-cyclo-hexen-1-carboxylic acid(3.78 g, 30 mmol, 1 equiv.). The mixture was stirred at room temperature until it became clear. Then, a solution of potassium iodide (29.90 g, 180 mmol, 6 equiv.) and iodine (7.98 g, 31.50 mmol, 1.05 equiv.) in water (73 mL) was added in one portion and the reaction mixture was protected from light and stirred at room temperature overnight. Extraction with DCM was performedthree times and the combined organic layers were washed successively with10% aqueous of sodium thiosulfate; 10% aqueous sodium hydrogencarbonate and water, dried over Na2SO4, filtered and concentrated under vacuum to give (4S)-4-iodo-6-oxabicyclo[3.2.1]octan-7-one (7.21 g 95%) as a yellow-white solid.

Reference： [1]Current Patent Assignee: BCI PHARMA - WO2017/191297, 2017, A1 Location in patent: Page/Page column 116; 120

65
[ 4771-80-6 ]
[ 119719-61-8 ]
[ 123536-66-3 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With potassium iodate; potassium iodide In water at 20℃; for 2.5h; Stage #2: With acetic acid In water at 20℃; for 3h; Overall yield = 96 %; Overall yield = 38.9 mg;	24 (Synthesis of 4-Iodo-6-oxabicyclo[3.2.1]octane-7-one) [First step]Water 120 mL was added to a 300 mL inner volume container equipped with a reflux condenser, a dropping funnel, a thermometer, and a stirrer.After mixing 12.6 g (0.06 mol) of potassium iodate and 19.5 g (0.12 mol) of potassium iodide, 20.0 g (0.16 mol) of the racemic body of 3-cyclohexene-1-carboxylic acid was added while stirring, while stirring. The reaction was carried out at room temperature (20°C) for 2.5 hours.[Second process]After completion of the reaction in the first step, 9.5 g (0.36 mol) of acetic acid was added to the obtained reaction solution and mixed, and the mixture was reacted at room temperature (20° C.) for 3 hours while stirring.[third process]After completion of the reaction in the second step, 23.0 g (0.02 mol) of a 13% by mass aqueous sodium sulfite solution was added to the obtained reaction solution, and the mixture was stirred at room temperature (20° C.).Then, the precipitated crystals are filtered.The obtained crystals were washed twice with 40 mL of water and dried, and they were obtained in the form of khaki crystals.(1S,4S,5S)-4-Iodo-6-oxabicyclo[3.2.1]octan-7-one and (1R,4R,5R)-4-Iodo-6-oxabicyclo[3.2.1 ] Octane-7-one mixture38.2 g (0.15 mole) (yield; 96%). It can be seen thatEven the racemate of 3-cyclohexene-1-carboxylic acid,The reaction also proceeds in the same manner as when (S)-3-cyclohexene-1-carboxylic acid is used.And obtaining oxabicyclooctane compounds
56 % ee	With N-iodo-succinimide; C₃₁H₂₇BrN₂O In dichloromethane; toluene at -50℃; for 48h; Inert atmosphere; Overall yield = 43%; Overall yield = 0.011 g; enantioselective reaction;

Reference： [1]Current Patent Assignee: UBE INDUSTRIES LIMITED - CN107540639, 2018, A Location in patent: Paragraph 0136-0144
[2]Klosowski, Daniel W.; Hethcox, J. Caleb; Paull, Daniel H.; Fang, Chao; Donald, James R.; Shugrue, Christopher R.; Pansick, Andrew D.; Martin, Stephen F. [Journal of Organic Chemistry, 2018, vol. 83, # 11, p. 5954 - 5968]

66
[ 4771-80-6 ]
[ 70-55-3 ]
C₁₄H₁₇NO₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 12h; Inert atmosphere;

Reference： [1]Xie, Changmin; Luo, Jisheng; Zhang, Yuping; Huang, Sha-Hua; Zhu, Lili; Hong, Ran [Organic Letters, 2018, vol. 20, # 8, p. 2386 - 2390]

67
[ 4771-80-6 ]
3-bromo-cyclohexanecarboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	With hydrogen bromide at 20℃; for 6h;	1 Example 1 3-cyclohexenecarboxylic acid II (25 g, 0.2 mol, commercially available) was added to a 40% hydrobromic acid solution (50 ml, 0.36 mol) at room temperature, stirred for 6 hours, extracted with ethyl acetate, concentrated, and separated on a silica gel column. 3-Bromo-cyclohexylcarboxylic acid III (8.2 g, yield 40%)

Reference： [1]Current Patent Assignee: YONGTAI PHARMACEUTICAL; ZHEJIANG YONGTAI TECHNOLOGY CO LTD - CN107880006, 2018, A Location in patent: Paragraph 0090-0091

68
[ 625-38-7 ]
[ 106-99-0 ]
[ 4771-80-6 ]

Yield	Reaction Conditions	Operation in experiment
89.1%	With hydroquinone at 240℃; Autoclave; Inert atmosphere;	4 Examples 1 to 4 use autoclave reactors The reaction takes place in a stainless steel autoclave equipped with high-speed stirring and cooling coils. The jacket heats the oil,Coil with cooling water.After the reactor is under negative pressure, deionized water will be prepared in proportion.Acrylic acid and hydroquinone were added to the reactor.Introduce nitrogen pressure to maintain the gauge pressure of 0.5MPa to start stirring.Speed is 800-1200r/min.The heat transfer oil is heated to the material temperature to 130-180°C.Pressing 1.3 butadiene with nitrogen at a constant speedThe reaction temperature was maintained at 150-260°C by adjusting the feed rate and coil cooling water. The reaction is cooled after 1-2.5 hours.Reaction pressure gauge 1.5MPa-3.5MPa sampling analysis,Gas chromatography is used for sample analysis (If continuous production is to be achieved, the reaction time can be controlled by the two reactors in series according to the kettle volume and the feed rate. Refer to the following tubular reaction examples for reaction parameters).After pressing the material into the distillation tower,Tower cauldron theoretical plate number about 30,The light components are removed from the twin towers to purify the finished product.Maintain negative pressure at absolute pressure 100Pa-10kPa, reflux ratio 4-7,Sample analysis after purificationGas chromatography was used for the analysis.Cyclohexene carboxylic acid content ≥ 99%.

Reference： [1]Current Patent Assignee: PUYANG SHENGHUADE CHEMICAL - CN107827733, 2018, A Location in patent: Paragraph 0017; 0018; 0019; 0020

69
[ 4771-80-6 ]
[ 56447-21-3 ]
[ 20893-19-0 ]

Yield	Reaction Conditions	Operation in experiment
50%	With oxalyl dichloride; 1,1'-sulfinylbisbenzene In dichloromethane at -78 - 20℃; for 1h; Inert atmosphere;	Chlorolactones 2a-l; General Procedure General procedure: To a solution of oxalyl chloride (0.65 mL, 7.5 mmol, 1.5 equiv) in CH2Cl2 (10 mL) cooled at -78 °C was added dropwise a solution of diphenyl sulfoxide (1.52 g, 7.5 mmol, 1.5 equiv) in CH2Cl2 (10 mL) under N2 atmosphere. After 10 min, a solution of alkenoic acid 1 (5 mmol, 1.0 equiv) in CH2Cl2 (10 mL) was added. The mixture was then allowed to warm up to r.t. and stirred for 1 h. Distilled H2O (30 mL) was added dropwise at 0 °C. After stirring for 10 min, the organic layer was separated and successively washed with brine (2 × 30 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated under reduced pressure. Purification by flash chromatography (silica gel, PE/EtOAc 10:1) afforded the corresponding chlorolactones. In an optimized procedure for chlorolactones 2e, 2f, and 2h, K2CO3 (3.45 g, 25 mmol, 5.0 equiv) and 18-crown-6 (66 mg, 0.025 mmol, 0.05 equiv) were added after the addition of substrate, then the mixture was allowed to warm up to r.t. and stirred for 5 h. For cyclopent-2-ene-1-acetic acid (1f), two chlorolactones cis-2f and 2f′ were obtained.

Reference： [1]Ding, Rui; Lan, Liyuan; Li, Shuhui; Liu, Yongguo; Yang, Shaoxiang; Tian, Hongyu; Sun, Baoguo [Synthesis, 2018, vol. 50, # 13, p. 2555 - 2566]

70
[ 4771-80-6 ]
[ 29110-74-5 ]
C₁₃H₁₃ClN₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With copper(I) thiophene-2-carboxylate; (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(5-methyl-2-(4-fluorophenyl)pyridine(-1H))-iridium(III) hexafluorophosphate; N,N,N?,N?-tetramethyl-N?-tert-butylguanidine; bathophenanthroline; iodomesitylene diacetate; In 1,4-dioxane; at 20℃; for 1h;Inert atmosphere; Irradiation;	General procedure: To a 20 ml or 40 ml viale quipped with a stir bar was added photocatalyst, nitrogen nucleophile, iodomesitylene dicarboxylate, copper salt, and ligand. Dioxane was added followed by addition of the base. The solution was sonicated for 1-3 min until it became homogeneous. Next, the solution was degassed by sparging with nitrogen for 5-10 min before sealing with Parafilm. The reaction was stirred and irradiated using two 34-W blue LED lamps (3 cm away, with cooling fan to keep the reaction at room temperature) for 1 h. The reaction mixture was removed from the light, cooled to ambient temperature, diluted with water (15 ml) and ethyl acetate (25 ml), and the aqueous layer was extracted with ethyl acetate (3 × 25 ml). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel to afford the desired decarboxylative C-N coupling product. For aniline substrates, a solution of these nitrogen nucleophiles in dioxane was used; additionally, if the iodomesitylene dicarboxylate is a liquid, its solution in dioxane was used.

Reference： [1]Nature,2018,vol. 559,p. 83 - 88

71
[ 4771-80-6 ]
[ 822-66-2 ]

Reference： [1]Organic Letters,2018,vol. 20,p. 4824 - 4827

72
[ 4771-80-6 ]
[ 517-89-5 ]
(R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl cyclohex-3-enecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
29%	Stage #1: shikonin With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0℃; for 0.25h; Inert atmosphere; Stage #2: 1,2,5,6-tetrahydrobenzoic acid In dichloromethane for 16h; Inert atmosphere;	3.1.3. General Procedure for the Acylation of Shikonin General procedure: A solution of shikonin in abs. CH2Cl2 (0.1 mmol/5 mL) was cooled to 0 C under argonatmosphere and DCC was added. DMAP was added after stirring for 15 min. After further stirring for15 min, the corresponding acid was added and stirring was continued for 14 h to 5 days with slowlywarming up to room temperature. After addition of 1 mL cyclohexane/0.1 mmol shikonin, the mixturewas concentrated under reduced pressure at room temperature to approx. 0.5 mL/0.1 mmol shikonin.The mixture was filtered over 3 mm silica and 2 mm celite (eluent: petroleum ether/CH2Cl2 = 1:0 to1:2). Product containing fractions were evaporated and submitted to flash CC and/or repeated PTLC(cyclohexane/CH2Cl2 mixtures). Due to the rapid decomposition of raw acylshikonin mixtures onevaporation to higher concentrations (c > approx. 0.2Macylshikonin) and degradation of acylshikoninson prolonged contact with silica, intermediate solutions were not to be concentrated to dryness and allisolation and purification steps had be performed at a good pace.

Reference： [1]Durchschein, Christin; Bauer, Rudolf; Kretschmer, Nadine; Hufner, Antje; Rinner, Beate; Stallinger, Alexander; Deutsch, Alexander; Lohberger, Birgit [Molecules, 2018, vol. 23, # 11]

73
[ 4771-80-6 ]
4-azapentacyclo[5.3.2.0^2,6.0^8,10]dodec-11-ene hydrochloride [ No CAS ]
(4-azatetracyclo[5.3.2.0^2,6.0^8,10]dodec-11-en-4-yl)(cyclohex-3-en-1-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
199 mg	With benzotriazol-1-ol; 1,2-dichloro-ethane; triethylamine In ethyl acetate at 20℃;	3.1.7. (4-Azatetracyclo[5.3.2. 02,6.08,10]dodec-11-en-4-yl)(cyclohex-3-en-1-yl)methanone 9 To a solution of 4-azapentacyclo[5.3.2.02,6.08,10]dodec-11-ene hydrochloride (200 mg, 1.03 mmol)in EtOAc (10 mL) were added 3-cyclohexene carboxylic acid (119 mg, 0.94 mmol), HOBt (190 mg,1.41 mmol), EDC (218 mg, 1.41 mmol), and triethylamine (0.6 mL, 4.14 mmol). The reaction mixturewas stirred at room temperature overnight. To the resulting suspension was then added water (10 mL)and the phases were separated. The organic phase was washed with saturated aqueous NaHCO3solution (10 mL) and brine (10 mL), dried over anh. Na2SO4 and filtered. Evaporation in vacuo ofthe organics gave RL-135 as a yellowish solid (259 mg, quantitative yield). Column chromatography(hexane/EtOAc mixture) gave 9 as a white solid (199 mg), m.p. 78-79 °C. IR (ATR) : 682, 710, 763,816, 839, 854, 887, 915, 940, 981, 1016, 1034, 1087, 1135, 1168, 1203, 1221, 1274, 1292, 1332, 1355, 1380,1431, 1620, 1651, 2870, 2926, 3022 cm1. 1H-NMR (400 MHz, CDCl3) : 0.10-0.19 (complex signal,2H, 90-H2), 0.86-0.96 (complex signal, 2H, 8'-H and 10'-H), 1.56-2.38 (complex signal, 6H, 2-Hax,5-Hax, 6-Hax, 2-Heq, 5-Heq, 6-Heq), 2.47 (m, 1H, 1-H), 2.56 (m, 1H, 2'-H or 6'-H), 2.67 (m, 1H, 6'-H or 2'-H), 2.81-2.89 (complex signal, 2H, 1'-H and 7'-H), 3.11-3.24 (complex signal, 2H, 3'-Ha and 5'-Ha),3.52-3.64 (complex signal, 2H, 3'-Hb and 5'-Hb), 3.50-3.64 (complex signal, 2H, 3'-Hb and 5'-Hb),5.61-5.84 (complex signal, 4H, 11'-H, 12'-H, 3-H and 4-H). 13C-NMR (100.5 MHz, CDCl3) : 4.03 and 4.06 (CH2, C9'), 9.9 (CH, C8' or C10'), 10.1 (CH, C100 or C80), 24.96 and 24.99 (CH2, C5 or C6), 25.1 and25.2 (CH2, C6 or C5), 27.40 and 27.43 (CH2, C2), 35.6 (CH, C10 or C70), 35.7 (CH, 70 or C10), 38.36 and38.38 (CH, C1), 42.7 (CH, C2' or C6'), 44.72 and 44.73 (CH, C6' or C2'), 49.68 and 49.74 (CH2, C3' or C5'), 50.6 (CH2, C5' or C3'), 125.88 and 125.94 (CH, C3 or C4), 126.3 and 126.4 (CH, C4 or C3),128.1 (CH, C11' or C12'), 129.5 and 129.6 (CH, C12' or C11'), 173.66 and 173.69 (C, CO). Anal. Calcd,for C18H23NO: C, 80.26; H, 8.61; N, 5.20. Found: C, 80.24; H, 8.73; N 5.19.

Reference： [1]Leiva, Rosana; McBride, Andrew; Binnie, Margaret; Webster, Scott P.; Vázquez, Santiago [Molecules, 2018, vol. 23, # 3]

74
[ 4771-80-6 ]
C₁₃H₂₂O₃ [ No CAS ]
C₂₀H₃₀O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid In toluene at 75 - 85℃;	4 The cooled reaction solution was transferred to a 50 L reactor equipped with a reflux apparatus, and 12 kg of toluene, 302.4 g of 3-cyclohexenecarboxylic acid (2.39 mol) and 40 g of p-toluenesulfonic acid were added, and the vacuum pump was opened to maintain a vacuum of -0.08 mPa. Between ~-0.085mPa, and heating to 75-85 °C, the water is refluxed. When there is no more water, the vacuum pump is turned off and the temperature is lowered to below 30 °C. The reaction solution is washed once with 5L of water, then distilled under reduced pressure. Remove toluene.

Reference： [1]Current Patent Assignee: JIANGSU TAITEER NEW MATERIAL TECH - CN109096227, 2018, A Location in patent: Paragraph 0039; 0051

75
[ 4771-80-6 ]
C₂₂H₂₂ClF₃N₂O₄S [ No CAS ]
C₂₉H₃₀ClF₃N₂O₅S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 96h;	18 Example I8 Into the solution of Intermediate 3 (75 mg, 0.15 mmol) and DIPEA (52.1 fll, 0.29S mmol) and cyclohex-3ene-1-carboxylic acid (IS.S mg, 0.15 mmol) in DMF (I mL) at rt was added HATU (6S.O mg, O.IS mmol) and stirred at rt for 4 days. it was purified by prep-HPLC (C-IS, Acetonitrile/water) to afford the title compound as a white solid (65 mg, 71%). ESI-MS m/z=609.14, 611.14 [M-Hr.

Reference： [1]Current Patent Assignee: ENANTA PHARMACEUTICALS INC - US2019/60258, 2019, A1 Location in patent: Paragraph 0229; 0230

76
[ 491-35-0 ]
[ 4771-80-6 ]
2-(cyclohex-3-en-1-yl)-4-methylquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	With 2-Picolinic acid; ferrous(II) sulfate heptahydrate; sodium bromate In water; dimethyl sulfoxide at 20℃; for 24h; Inert atmosphere; Irradiation;

Reference： [1]Li, Zhenlong; Wang, Xiaofei; Xia, Siqi; Jin, Jian [Organic Letters, 2019]

77
[ 4771-80-6 ]
[ 100-51-6 ]
[ 91503-67-2 ]

Yield	Reaction Conditions	Operation in experiment
96%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In chloroform	R.158.5 Preparation of benzyl cyclohex-3-ene-1-carboxylate Reference Example 158-5 Preparation of benzyl cyclohex-3-ene-1-carboxylate racemate Cyclohex-3-ene-1-carboxylic acid (926 μL), 4-dimethylaminopyridine (96.6 mg), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.98 g), and chloroform (16 mL) were mixed, and the resulting mixture was stirred at room temperature for 15 minutes. To the reaction mixture was added benzylalcohol (984 μL), the resulting mixture was stirred overnight, then benzylalcohol (246 μL) was additionally added thereto, and the resulting mixture was stirred overnight. The reaction mixture was concentrated under reduced pressure until the volume was reduced by approximately half, and the resulting residues were purified by silica gel column chromatography (solvent: hexane/ethyl acetate=100/0 to 67/33) to give the title compound (1.64 g) (yield 96%) as a colorless oil. MS(ESI) m/z: 217 [M+H]+

Reference： [1]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION; UBE INDUSTRIES LIMITED - US2019/185479, 2019, A1 Location in patent: Paragraph 1833; 1834; 1835

78
[ 4771-80-6 ]
[ 4559-70-0 ]
3-cyclohexenyldiphenylphosphine oxide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With dmap; dihydrogen peroxide; dicyclohexyl-carbodiimide In dichloromethane at 40℃; for 2h; Stage #2: Diphenylphosphine oxide With [2,2]bipyridinyl; copper(II) sulfate In chlorobenzene at 40℃;	10 Example 10: Synthesis of 3-cyclohexenyldiphenylphosphine oxide Using 3-cyclohexene-1-carboxylic acid and diphenylphosphine as raw materials, the reaction steps are as follows:Add 3-cyclohexene-1-carboxylic acid (126 mg, 1 mmol), 4-dimethylaminopyridine (DMAP, 18.3 mg, 0.15 mmol), and dicyclohexylcarbodiimide (DCC, 340 mg) to the reaction flask. , 1.65 mmol), hydrogen peroxide (57 μL, 1.9 mmol) and dichloromethane (5 mL), stirred at 40 ° C. for 2 hours, filtered, and the solvent in the filtrate was distilled off to obtain a concentrate;To the concentrate were added copper sulfate (8 mg, 0.05 mmol), 2,2'-bipyridine (7.8 mg, 0.05 mmol), chlorobenzene (1 mL), and diphenylphosphine oxide (50.5 mg, 0.25 mmol), The reaction was stirred at 40 oC, and TLC monitored until the end of the reaction;The crude product obtained after the reaction was separated by column chromatography (petroleum ether: acetone = 4: 1) to obtain the target product (yield 80%).

Reference： [1]Current Patent Assignee: SOOCHOW UNIVERSITY (SUZHOU) - CN110256489, 2019, A Location in patent: Paragraph 0023

79
[ 4771-80-6 ]
[ 89892-96-6 ]
3-bromo-cyclohexanecarboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen bromide; acetic acid In dichloromethane at 5 - 30℃; for 0.75h; Overall yield = 0.27 g;	1; 1-7 [Reference Example 1] <Synthesis method of mixture of 3-bromocyclohexane-1-carboxylic acid and 4-bromocyclohexane-1-carboxylic acid> After mixing 360 mL of an acetic acid solution containing 30% by mass of hydrogen bromide and 380 mL of methylene chloride cooled to 5 ° C. or less, 191 g of 3-cyclohexene-1-carboxylic acid was added while maintaining the internal temperature at 10 ° C. or less.A solution previously dissolved in 190 mL of methylene chloride was added dropwise over 15 minutes.After completion of the dropwise addition, the mixture was stirred for 30 minutes while maintaining the internal temperature at 20 to 30 ° C., and then allowed to stand at room temperature (23 ° C.) for 14 hours.Next, the reaction solution was diluted with 190 mL of ethyl acetate and 380 mL of water, and the separated upper layer (aqueous layer) was removed. The lower layer (organic layer) was washed four times with 380 mL of water and once with 380 mL of saturated saline. And 20 g of sodium sulfate.After removing sodium sulfate by filtration, the organic layer was concentrated under reduced pressure (50 mmHg, external temperature 35 ° C.) by an evaporator to obtain a mixture of 3-bromocyclohexane-1-carboxylic acid and 4-bromocyclohexane-1-carboxylic acid. Was.As a result of analysis by 1H-NMR, the molar ratio of 4-bromocyclohexane-1-carboxylic acid to 3-bromocyclohexane-1-carboxylic acid was 58:42. [Example 1] Prepared by the synthesis method described in Reference Example 1,After 1 g of a mixture of 3-bromocyclohexane-1-carboxylic acid and 4-bromocyclohexane-1-carboxylic acid was dispersed in 3 mL of n-hexane, the mixture was stirred at 0 ° C. for 1 hour.After filtering the precipitated solid, it was washed three times with 2 mL of n-hexane.Thereafter, it was air-dried at 25 ° C. until there was no change in weight, to obtain 0.27 g (yield: 27%) of a white solid. As a result of analyzing the obtained white solid by 1H-NMR,The molar ratio of 4-bromocyclohexane-1-carboxylic acid to 3-bromocyclohexane-1-carboxylic acid was 95: 5.

Reference： [1]Current Patent Assignee: FUJIFILM HOLDINGS CORP. - JP2020/26413, 2020, A Location in patent: Paragraph 0029-0036

80
[ 124-38-9 ]
[ 1165952-91-9 ]
[ 4771-80-6 ]
[ 62115-15-5 ]

Yield	Reaction Conditions	Operation in experiment
	With triethanolamine; tetraethylammonium iodide; water In N,N-dimethyl-formamide at 20℃; for 5h; Electrochemical reaction; Overall yield = 80 percent;

Reference： [1]Buckley, Benjamin R.; Elmorsy, Saad S.; Malkov, Andrei V.; Mashaly, Mohammad A.; Said, Samy B.; Sheta, Ahmed M. [Chemical Science, 2020, vol. 11, # 34, p. 9109 - 9114]

81
[ 4771-80-6 ]
[ 24324-17-2 ]
9-fluorenylmethyl cyclohexan-3-enylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
22 g	Stage #1: 1,2,5,6-tetrahydrobenzoic acid With triethylamine In 5,5-dimethyl-1,3-cyclohexadiene at 20℃; for 0.5h; Inert atmosphere; Stage #2: With diphenylphosphoranyl azide In 5,5-dimethyl-1,3-cyclohexadiene at 110℃; for 4.5h; Stage #3: 9-Fluorenylmethanol In toluene at 140℃; for 12h;	3 Dissolve 10g racemic 3-cyclohexenecarboxylic acid in 100ml xylene,Add 8.9 g of triethylamine dropwise under nitrogen protection,Then stir at room temperature for 30 minutes,Then slowly add 23.1g of diphenyl azide phosphate,After adding, continue to stir for 1.5 hours.Warm up to 110°C,Incubate and react for 3 hours.Add 17.2g of fluorene methanol,The reaction was continued at 140°C for 12 hours.Cool to room temperature,Add 100ml of saturated aqueous sodium bicarbonate solution,Separate the organic layer,After the aqueous phase was extracted with ethyl acetate, the organic phases were combined,Wash with saturated brine,Dry with anhydrous sodium sulfate,Concentrate under reduced pressure to obtain 22 g of the crude product fluorene methyl cyclohexenyl carbamate 2c.

Reference： [1]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES - CN111825563, 2020, A Location in patent: Paragraph 0008; 0027-0028

82
[ 4771-80-6 ]
[ 74903-79-0 ]
(Z)-N-((cyclohex-3-ene-1-carbonyl)oxy)-4-methoxybenzimidoyl chloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 25℃; for 4h; Inert atmosphere;

Reference： [1]Li, Xiaojuan; Ni, Shengyang; Pan, Yi; Wang, Yi; Zhang, Qiang; Zhang, Weigang [Angewandte Chemie - International Edition, 2020, vol. 59, # 49, p. 21875 - 21879][Angew. Chem., 2020, vol. 132, # 49, p. 22059 - 22063,5]

83
[ 4771-80-6 ]
[ 2627-86-3 ]
[ 5708-19-0 ]

Yield	Reaction Conditions	Operation in experiment
108 g	Stage #1: 1,2,5,6-tetrahydrobenzoic acid; (<i>S</i>)-1-phenyl-ethylamine In acetone at 40℃; for 2h; Stage #2: With hydrogenchloride In dichloromethane; water for 2h;	1.S1-1.S2 S1. Add 200g of compound (I) to 1L of acetone and dissolve under reflux for 1h. Add 192.1g of compound (II) to 0.5L of acetone and add dropwise to the reaction solution, slowly decrease the temperature to 40°C and react for 2h, then cool to 20~25°C, suction filtration, filter cake 40~45°C blast drying to obtain 270g solid, add 8 times acetone to recrystallize, then cool to 20~25°C to crystallize, suction filter, filter cake 40~45°C blast drying 170 g of compound (III) is obtained, S2. Add 170g of compound (III) to 3L of dichloromethane, add 3L of 2N HCl solution and stir for 2h, separate the layers, the water layer is back-extracted with 2L of dichloromethane, and the organic layer is washed with 3L of saturated sodium chloride solution. Dry with 100g of anhydrous sodium sulfate and concentrate to dryness at 40~45°C to obtain 108g of compound (IV),

Reference： [1]Current Patent Assignee: NANJING ANHONG YUANHUA PHARMACEUTICAL INDUSTRY INVESTMENT PARTNERSHIP (LIMITED PARTNERSHIP) - CN112321613, 2021, A Location in patent: Paragraph 0071-0074-0076

84
[ 4771-80-6 ]
[ 3886-69-9 ]
[ 5709-98-8 ]

Yield	Reaction Conditions	Operation in experiment
108 g	Stage #1: 1,2,5,6-tetrahydrobenzoic acid; (R)-1-phenyl-ethyl-amine In acetone at 40℃; for 2h; Stage #2: With hydrogenchloride In dichloromethane; water for 2h;	3.S1-3.S2 S1. Using compound (I) and compound (II) as starting materials, the chemical name of compound (I) is 3-cyclohexene-1-carboxylic acid, and the structural formula is compound (II): 200g of compound (I) was added to 1L of acetone, refluxed for 1h, 192.1g of compound (II) was dissolved in 0.5L of acetone and added dropwise to the reaction solution, slowly cooled down to 40°C for 2h, and then cooled to 20~ 25, suction filtration, filter cake 4045 blast drying to obtain 270g solid, add 8 times acetone to recrystallize, then cool to 2025 crystallization, suction filtration, filter cake 4045 blast drying to obtain 170g Compound (III), S2. Add 170g of compound (III) to 3L of dichloromethane, add 3L of 2N HCl solution and stir for 2h, separate the layers, the water layer is back-extracted with 2L of dichloromethane, and the organic layer is washed with 3L of saturated sodium chloride solution. Dry with 100g of anhydrous sodium sulfate and concentrate to dryness at 40~45°C to obtain 108g of compound (IV),

Reference： [1]Current Patent Assignee: NANJING ANHONG YUANHUA PHARMACEUTICAL INDUSTRY INVESTMENT PARTNERSHIP (LIMITED PARTNERSHIP) - CN112321613, 2021, A Location in patent: Paragraph 0122-0124-0128

85
[ 4771-80-6 ]
C₁₃H₁₈O₅ [ No CAS ]
C₂₀H₂₆O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 6h;	1 Compound 1-c (20mmol, 5.080g) and compound 1-e-7 (24mmol, 3.024g) were dissolved in 70mL of dichloromethane, DMAP (20mmol, 2.440g) was added, and EDC.HCl ( 40mmol, 7.640g), warmed to room temperature naturally, and reacted with magnetic stirring for 6h. After the reaction, the reaction solution was extracted with dichloromethane three times, the organic phase was taken, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The concentrate was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 6:1, v /v), a colorless oily liquid product 1-f-7 is obtained.

Reference： [1]Current Patent Assignee: HAINAN MEDICAL UNIVERSITY - CN113527244, 2021, A Location in patent: Paragraph 0037-0040

86
[ 6479-18-1 ]
[ 4771-80-6 ]
3-(cyclohex-3-en-1-yl)-1-methylquinoxalin-2(1H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With ammonium peroxydisulfate In dimethyl sulfoxide at 20℃; for 24h; Inert atmosphere; Irradiation;	General procedure for the prepration of 3- alkylquinoxalin-2(1H)-ones General procedure: To a solution of quinoxalin-2(1H)-ones 1 (0.3 mmol) and aliphatic acid 2 (0.75 mmol) in DMSO (3 mL) was added (NH4)2S2O8 (0.9 mmol). The reaction mixture was stirred at room temperature under the irradiation of 10 W blue LED lamps (440-445 nm) under N2 atmosphere conditions. The progress of the reaction was monitored by TLC. The reaction typically took within 24 hours. After completion, water (10mL) was added and the mixture was extracted with EtOAc (10 mL× 3), the solvent was then removed under vacuum. The residue was purified by flash column chromatography using a mixture of petroleum ether and ethyl acetate as eluent to give the desired products 3.

Reference： [1]Hong, Yun-Yun; Peng, Zhen; Ma, Hui; Zhu, Qi; Xu, Xiang-Qin; Yang, Li-Hua; Xie, Long-Yong [Tetrahedron Letters, 2022, vol. 89]

87
[ 4771-80-6 ]
[ 1193-82-4 ]
trans-4-(phenylthio)-6-oxabicyclo[3.2.1]octan-7-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	Stage #1: racemic methyl phenyl sulfoxide With oxalyl dichloride In acetonitrile at 0℃; Reflux; Stage #2: 1,2,5,6-tetrahydrobenzoic acid In acetonitrile for 10h; Reflux;	General Procedure for arylsulfenylation of unsaturated acids with PhSOCH3 and (COCl)2 in CH3CN. General procedure: To a solution of ArSOCH3 (15 mmol, 3 equivalents) in acetonitrile cooled at 0 °C was addeddropwise a solution of oxalyl chloride (3.75 mmol, 0.75 equivalents) in acetonitrile (10 mL). Themixture was stirred for 10 min at 0 °C. It was then allowed to warm to room temperature and heatedto reflux. Then an unsaturated acid (1a-w) (5 mmol, 1 equivalent) was added and the reactionmixture continued to reflux for 10 h. After cooling to room temperature, the reaction mixture wasthen concentrated on a rotary evaporator and the residue redissolved in CH2Cl2 (100 mL). Theresulting solution was washed with saturated NaHCO3 and brine. The organic phase was dried oversodium sulfate, filtered, concentrated, and the residue purified by flash chromatography on silicagel column to give the arylsulfenylation lactones. (2a-z). The products 2a-w were obtained usingPhSOCH3 and 2x-z obtained using methyl p-methylphenyl sulfoxide, methyl p-fluorophenylsulfoxide, and methyl p-chlorophenyl sulfoxide respectively.

Reference： [1]Liang, Sen; Liu, Yongguo; Sun, Baoguo; Tian, Hongyu; Wang, Hao; Wang, Yinong; Wang, Yutong; Xiang, Fan [Tetrahedron, 2022, vol. 105]

88
[ 4771-80-6 ]
[ 3440-28-6 ]
[ 40496-47-7 ]

Yield	Reaction Conditions	Operation in experiment
44%	Stage #1: 1,2,5,6-tetrahydrobenzoic acid; 3-benzoylaminopropionic acid With 4-dimethylaminopyridine; NHPI; diisopropyl-carbodiimide In dichloromethane at 20℃; for 1h; Stage #2: With nickel(II) chloride ethylene glycol dimethyl ether complex; sodium iodide; 2,6-di(4,5-dihydro-1,3-oxazol-2-yl)-4-methoxypyridine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 2.5h; Electrochemical reaction;	General procedure General procedure: The general procedure proceeds as follows: to a mixture of acid components (the less expensive of which is used in 3 equiv.) in CH2Cl2 are added diisopropylcarbodiimide (DIC) and N-hydroxyphthalimide (NHPI) (1.1 equiv. each relative to total acid quantity, 4.4 equiv. total) along with catalytic amount of 4-dimethylaminopyridine (10 mol% to total acid quantity, 0.4 equiv. total). After stirring for 1 h, without any solvent removal, the solution is diluted with N,N-dimethylformamide and NiCl2•dme along with L4 are added (roughly 5 mol% each relative to total acid quantity, 20 mol% total), followed by the addition of NaI (0.2 M). Electrolysis using a standard ElectraSyn2.0 potentiostat (Zn anode and Ni foam cathode) for about 2.5 h (0.1 mmol scale) followed by standard workup and purification delivers the coupled product.

Reference： [1]Zhang, Benxiang; Gao, Yang; Hioki, Yuta; Oderinde, Martins S.; Qiao, Jennifer X.; Rodriguez, Kevin X.; Zhang, Hai-Jun; Kawamata, Yu; Baran, Phil S. [Nature, 2022, vol. 606, # 7913, p. 313 - 318]

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
Accessible (Haz class 3, 4, 5 or 8), International	USD 200+

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	4771-80-6	MDL No. :	MFCD00013781
Formula :	C₇H₁₀O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	VUSWCWPCANWBFG-UHFFFAOYSA-N
M.W :	126.15	Pubchem ID :	20903
Synonyms :

Num. heavy atoms :	9
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.57
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	34.95
TPSA :	37.3 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.17 cm/s

[ CAS No. 4771-80-6 ] {[proInfo.proName]}

Quality Control of [ 4771-80-6 ]

Related Doc. of [ 4771-80-6 ]

Product Details of [ 4771-80-6 ]

Calculated chemistry of [ 4771-80-6 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 4771-80-6 ]

Application In Synthesis of [ 4771-80-6 ]

[ 4771-80-6 ] Synthesis Path-Upstream 1~5

[ 4771-80-6 ] Synthesis Path-Downstream 1~88

Related Functional Groups of
[ 4771-80-6 ]

Alkenes

Aliphatic Cyclic Hydrocarbons

Carboxylic Acids

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Log Po/w (iLOGP) :	1.43
Log Po/w (XLOGP3) :	1.27
Log Po/w (WLOGP) :	1.43
Log Po/w (MLOGP) :	1.13
Log Po/w (SILICOS-IT) :	0.93
Consensus Log Po/w :	1.24

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.56

Log S (ESOL) :	-1.36
Solubility :	5.55 mg/ml ; 0.044 mol/l
Class :	Very soluble
Log S (Ali) :	-1.65
Solubility :	2.81 mg/ml ; 0.0223 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.18
Solubility :	83.3 mg/ml ; 0.661 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.91

Signal Word:	Danger	Class:	8
Precautionary Statements:	P234-P260-P264-P280-P301+P330+P331+P310-P303+P361+P353+P310+P363-P304+P340+P310-P305+P351+P338+P310-P312-P390-P405-P406-P501	UN#:	3265
Hazard Statements:	H312-H314	Packing Group:	Ⅲ
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
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P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling