Name: 63909-58-0|Diethyl 4-fluorobenzylphosphonate|95%
Brand: Ambeed
SKU: A634624
Price: 31.0 USD
Availability: InStock
Rating: 98 (35 reviews)

1
[ 63909-58-0 ]
[ 157735-68-7 ]

Yield	Reaction Conditions	Operation in experiment
	With sulfur trioxide at 0℃;
	Multi-step reaction with 2 steps 1: concd HCl / Heating 2: SO₃ / 0 °C

Reference： [1]Montoneri, E.; Savarino, P.; Viscardi, G.; Gallazzi, M. C. [Phosphorus, Sulfur and Silicon and the Related Elements, 1994, vol. 86, # 1-4, p. 145 - 156]
[2]Montoneri, E.; Savarino, P.; Viscardi, G.; Gallazzi, M. C. [Phosphorus, Sulfur and Silicon and the Related Elements, 1994, vol. 86, # 1-4, p. 145 - 156]

2
[ 124-38-9 ]
[ 63909-58-0 ]
[ 364046-30-0 ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium at -78℃;

Reference： [1]Beck; Magnin-Lachaux; Herdtweck; Doemling [Organic letters, 2001, vol. 3, # 18, p. 2875 - 2878]

3
[ 63909-58-0 ]
[ 100-10-7 ]
(E)-4-(4-fluorostyryl)-N,N-dimethylaniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 20℃;

Reference： [1]Kung; Lee; Zhuang; Kung; Hou; Ploessl [Journal of the American Chemical Society, 2001, vol. 123, # 50, p. 12740 - 12741]

4
[ 3612-20-2 ]
[ 63909-58-0 ]
[ 193357-62-9 ]

Yield	Reaction Conditions	Operation in experiment
	With 1,3-dimethyl-2-imidazolidinone; sodium hydride at 20℃; for 0.333333h;
	With sodium hydride In N,N-dimethyl-formamide at 0℃;	b Step b: Synthesis of l-benzyI-4-(4-fluorobenzyIidene)piperidine; To a solution of the compound obtained from step a above (0.38 g, 1.72 mmol) and N-benzyl-4-piperidone (0.326 g, 1.72 mmol) in dimethylformamide (3 ml) was added sodium hydride (0.10 g, 4.3 mol) at 0°C and stirred for overnight. The reaction mixture was quenched with ice-cold water followed by the addition of ethyl acetate. The organic layer was separated, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to furnish the title compound (0.40 g).

Reference： [1]McCauley, John A.; Theberge, Cory R.; Romano, Joseph J.; Billings, Susan B.; Anderson, Kenneth D.; Claremon, David A.; Freidinger, Roger M.; Bednar, Rodney A.; Mosser, Scott D.; Gaul, Stanley L.; Connolly, Thomas M.; Condra, Cindra L.; Xia, Menghang; Cunningham, Michael E.; Bednar, Bohumil; Stump, Gary L.; Lynch, Joseph J.; Macaulay, Alison; Wafford, Keith A.; Koblan, Kenneth S.; Liverton, Nigel J. [Journal of Medicinal Chemistry, 2004, vol. 47, # 8, p. 2089 - 2096]
[2]Current Patent Assignee: SUN PHARMACEUTICAL INDUSTRIES LIMITED - WO2006/16237, 2006, A2 Location in patent: Page/Page column 29

5
[ 352-11-4 ]
[ 122-52-1 ]
[ 63909-58-0 ]

Yield	Reaction Conditions	Operation in experiment
90%	at 190℃; for 6h;	1.1 (1) Synthesis of intermediate [diethyl 4-fluorobenzylphosphonate] Add in a 50ml single-mouth flask2.51 g of 4-fluorobenzyl chloride (0.01 mol)And 6.85 mL of triethyl phosphite (0.04 mol). Heat to 190 ° C and stir. After refluxing for 6 h, the reaction was cooled to room temperature, and excess phosphorous acid was removed by distillation under reduced pressure.Triethyl ester. After cooling, n-hexane was added to the system to produce a white precipitate.Dry to give a white solid 2.21g.The yield was 90%.
	at 150℃; for 15h;
	at 140℃; for 4h;

	In tetrahydrofuran for 4h; Reflux;
	for 4h; Reflux;

Reference： [1]Current Patent Assignee: SUN YAT-SEN UNIVERSITY (CHINA) - CN108424346, 2018, A Location in patent: Paragraph 0030-0033
[2]McCauley, John A.; Theberge, Cory R.; Romano, Joseph J.; Billings, Susan B.; Anderson, Kenneth D.; Claremon, David A.; Freidinger, Roger M.; Bednar, Rodney A.; Mosser, Scott D.; Gaul, Stanley L.; Connolly, Thomas M.; Condra, Cindra L.; Xia, Menghang; Cunningham, Michael E.; Bednar, Bohumil; Stump, Gary L.; Lynch, Joseph J.; Macaulay, Alison; Wafford, Keith A.; Koblan, Kenneth S.; Liverton, Nigel J. [Journal of Medicinal Chemistry, 2004, vol. 47, # 8, p. 2089 - 2096]
[3]Zhang, Yanxiu; Cao, Chao-Tun; Zhang, Jingyuan; Cao, Chenzhong [Journal of Physical Organic Chemistry, 2017, vol. 30, # 12]
[4]Cao, Chao-Tun; Yan, Lu; Cao, Chenzhong [Journal of Physical Organic Chemistry, 2021, vol. 34, # 9]
[5]Cao, Chaotun; Zeng, Zhao; Cao, Chenzhong [Journal of Physical Organic Chemistry, 2022, vol. 35, # 4]

6
[ 6515-21-5 ]
[ 63909-58-0 ]
[ 848487-62-7 ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: diethyl (4-fluorobenzyl)phosphonate With 18-crown-6 ether; sodium methylate In N,N-dimethyl-formamide at 20℃; for 0.0833333h; Stage #2: 4-methoxymethoxy-benzaldehyde With 18-crown-6 ether In N,N-dimethyl-formamide at 20 - 120℃; for 6h;

Reference： [1]Lion, Cedric J.; Matthews, Charles S.; Stevens, Malcolm F. G.; Westwell, Andrew D. [Journal of Medicinal Chemistry, 2005, vol. 48, # 4, p. 1292 - 1295]

7
[ 13709-05-2 ]
[ 63909-58-0 ]
[ 848487-63-8 ]

Yield	Reaction Conditions	Operation in experiment
92%	Stage #1: diethyl (4-fluorobenzyl)phosphonate With 18-crown-6 ether; sodium methylate In N,N-dimethyl-formamide at 20℃; for 0.0833333h; Stage #2: 3-methoxymethoxybenzaldehyde With 18-crown-6 ether In N,N-dimethyl-formamide at 20 - 120℃; for 6h;

Reference： [1]Lion, Cedric J.; Matthews, Charles S.; Stevens, Malcolm F. G.; Westwell, Andrew D. [Journal of Medicinal Chemistry, 2005, vol. 48, # 4, p. 1292 - 1295]

8
[ 5533-04-0 ]
[ 63909-58-0 ]
[ 115032-50-3 ]

Yield	Reaction Conditions	Operation in experiment
89%	Stage #1: diethyl (4-fluorobenzyl)phosphonate With 18-crown-6 ether; sodium methylate In N,N-dimethyl-formamide at 20℃; for 0.0833333h; Stage #2: 2-(methoxymethoxy)benzaldehyde With 18-crown-6 ether In N,N-dimethyl-formamide at 20 - 120℃; for 6h;

Reference： [1]Lion, Cedric J.; Matthews, Charles S.; Stevens, Malcolm F. G.; Westwell, Andrew D. [Journal of Medicinal Chemistry, 2005, vol. 48, # 4, p. 1292 - 1295]

9
[ 459-46-1 ]
[ 122-52-1 ]
[ 63909-58-0 ]

Yield	Reaction Conditions	Operation in experiment
100%	at 160℃; for 6h; Inert atmosphere;	27 Example 27: Diethyl (4-fluorobenzyl) phosphonate (30c) A solution of 1-(bromomethyl)-4-fluorobenzene (0.659 mL, 5.13 mmol) in triethylphosphite (3 mL) was stirred at 160° C. for 6 hours under nitrogen conditions. The volatile solvent was removed by distillation under reduced pressure, and the residue was purified by column chromatography (elution solvent: methanol/dichloromethane=1/50) to obtain a clear oily compound 30c (diethyl (4-fluorobenzyl) phosphonate; 1.26 g, 100%) was synthesized.
98%	at 80℃; for 17h;
96%	at 150℃; for 2h;

57%	at 170℃; for 4h;
	at 140℃;
	at 150℃; for 8h;	a EXPERIMENTAL; Synthesis of 4-(4-fluorobenzyl)piperidine; Step a: Synthesis of diethyl (4-fluorobenzyl)phosphonate; A mixture of the compound 4-fluorobenzyl bromide (1.50 g, 8.4 mmol) and triethylphosphite (1.20 g, 9.32 mmol) was stirred at 150 °C for 8 hours to furnish the title compound (2.2 g). This compound was used as such in the next step without purification.
	In 1,4-dioxane for 20h; Inert atmosphere; Reflux;
	In neat (no solvent) at 130℃; for 20h;	Preparation of (E)-stilbenes 10-13 and 16-22 via Horner-Wadsworth-Emmons reaction General procedure: A mixture of a suitable benzyl bromide (1 mmol) and excess triethylphosphite were stirred at 130 °C for 20 h. Removal of the remaining phosphite by vacuum distillation furnished the desired phosphonate as the residue. This intermediate was dissolved in 2 mL of dry DMF, contained in a flame-dried round-bottomed flask under a nitrogen atmosphere. Next, a solution of NaOMe (0.73 equiv) in methanol was added dropwise. The contents of the flask were cooled to 0 °C, upon which the aldehyde (0.67 equiv) was added. The resulting mixture was then successively stirred at room temperature for 1 h, heated to reflux temperature for another hour and left standing overnight. Afterward, a mixture of water and methanol (1:1) was added, which provided the desired stilbene as a precipitate. A second crop of crystals was harvested from the mother liquor.
	at 130℃; for 20h;	B.2 General procedure: [0383] Preparation of Stilbenes 90 and 91 Via Horner-Wadsworth-Emmons Reaction. [0384] A mixture of a suitable benzyl bromide (1 mmol) and excess triethyl phosphite are stirred at 130° C. for 20 h. Removal of the remaining phosphite by vacuum distillation furnishes the desired phosphonate as the residue. This intermediate is dissolved in 2 mL of dry dimethylformamide, contained in a flame-dried round-bottomed flask under a nitrogen atmosphere. Next, a solution of sodium methoxide (0.73 equiv.) in methanol is added dropwise. The contents of the flask is cooled to 0° C., upon which the aldehyde (0.67 equiv.) is added. The resulting mixture is then successively stirred at room temperature for 1 h, heated to reflux temperature for another hour and left standing overnight. [0385] Afterward, a mixture of water and methanol (1:1) is added, which provides the desired stilbene as a precipitate. A second crop of crystals can be harvested from the mother liquor.
	at 87℃; Inert atmosphere;	7.1 Step 1: diethyl 4-fluorobenzylphosphonate Step 1: diethyl 4-fluorobenzylphosphonate[002121 A mixture of triethyl phosphite (3.03 g, 18.25 mmol) and 1-(bromomethyl)-4-fluorobenzene (3.00 g, 15.87 mmol) was stirred under N2 at 87 °C overnight. The mixture was cooled to room temperature. The reaction mixture was used directly for the next step without further operation.
	at 160℃; for 5h; Inert atmosphere;	Diethyl (2,3-dichlorobenzyl)phosphonate General procedure: A flask was charged with 1-(bromomethyl)-2,3-dichlorobenzene (1.0 g, 4.17 mmol) and triethyl phosphite (1.39 g, 8.34 mmol). The flask was fitted with a reflux condensor and heated to 160 °C under a gentle stream of nitrogen (to aid in the removal of ethyl bromide) for 5 h. The reaction was cooled to room temperature, and concentrated by rotary evaporation under high vaccuum (bath temp 70 °C) to give 1.317 g (quant.) as a colorless oil which was used without purification.
	With tetra-(n-butyl)ammonium iodide at 130℃; for 6h;	General Procedure for Arbuzov Reaction (8a,b and 14a-f) General procedure: Triethyl phosphite (1.6 equiv) was added to aryl bromide (1.0 equiv) containing acatalytic amount of tetrabutylammonium iodide (0.01 equiv) and the reaction mixture washeated at 130 °C for 6 h. Excess triethyl phosphite was removed by heating at 80 °C undervacuum. The aryl phosphonate was obtained as colorless oil, which was used for the next stepwithout further purification.
3.8 g	at 80℃; for 16h; Sealed tube;	11.1 Step-1: Synthesis of diethyl (4-fluorobenzyl) phosphonate: In a sealed tube Cpd 1 (2.5 gm) was added triethylphosphite (1.5 eq) at 25 °C and heated to at 80 °C for 16 h (progress of the reaction was monitored by TLC), the reaction mixture was cooled to 25 °C, then crude product was purified by column chromatography on silica (ethyl acetate; (0303) Hexane 3:7) to yield Cpd 2 (3.8 gm) as a pale yellow liquid.
	With tetra-(n-butyl)ammonium iodide at 130℃; for 6h;
	at 87℃; Inert atmosphere;

Reference： [1]Current Patent Assignee: KOREA INSTITUTE OF SCIENCE AND TECHNOLOGY - KR2020/142215, 2020, A Location in patent: Paragraph 0365-0368
[2]Location in patent: experimental part Hong, Myeng Chan; Kim, Yun Kyung; Choi, Jae Yong; Yang, Si Qiang; Rhee, Hakjune; Ryu, Young Hoon; Choi, Tae Hyun; Cheon, Gi Jeong; An, Gwang Il; Kim, Hye Yun; Kim, Youngsoo; Kim, Dong Jin; Lee, Jun-Seok; Chang, Young-Tae; Lee, Kyo Chul [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 22, p. 7724 - 7730]
[3]Imamura, Shinichi; Nishikawa, Youichi; Ichikawa, Takashi; Hattori, Taeko; Matsushita, Yoshihiro; Hashiguchi, Shohei; Kanzaki, Naoyuki; Iizawa, Yuji; Baba, Masanori; Sugihara, Yoshihiro [Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 2, p. 397 - 416]
[4]Kung; Lee; Zhuang; Kung; Hou; Ploessl [Journal of the American Chemical Society, 2001, vol. 123, # 50, p. 12740 - 12741]
[5]Lion, Cedric J.; Matthews, Charles S.; Stevens, Malcolm F. G.; Westwell, Andrew D. [Journal of Medicinal Chemistry, 2005, vol. 48, # 4, p. 1292 - 1295]
[6]Current Patent Assignee: SUN PHARMACEUTICAL INDUSTRIES LIMITED - WO2006/16237, 2006, A2 Location in patent: Page/Page column 29
[7]Location in patent: experimental part Sorensen, Thomas J.; Nielsen, Merete F. [Central European Journal of Chemistry, 2011, vol. 9, # 4, p. 610 - 618]
[8]Roman, Bart I.; De Coen, Laurens M.; Mortier, Séverine Thérèse F.C.; De Ryck, Tine; Vanhoecke, Barbara W.A.; Katritzky, Alan R.; Bracke, Marc E.; Stevens, Christian V. [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 17, p. 5054 - 5063]
[9]Current Patent Assignee: GHENT UNIVERSITY - US2015/11620, 2015, A1 Location in patent: Paragraph 0383-0385
[10]Current Patent Assignee: SHENZHEN DONGYANGGUANG INDUSTRIAL DEVELOPMENT CO LTD - WO2015/90232, 2015, A1 Location in patent: Paragraph 00212
[11]Degnan, Andrew P.; Maxwell, Darrell; Balakrishnan, Anand; Brown, Jeffrey M.; Easton, Amy; Gulianello, Michael; Hanumegowda, Umesh; Hill-Drzewi, Melissa; Miller, Regina; Santone, Kenneth S.; Senapati, Arun; Shields, Eric E.; Sivarao, Digavalli V.; Westphal, Ryan; Whiterock, Valerie J.; Zhuo, Xiaoliang; Bronson, Joanne J.; Macor, John E. [Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 24, p. 5871 - 5876]
[12]Harmalkar, Dipesh S.; Lee, Sung-Jin; Lu, Qili; Kim, Mi Il; Park, Jaehyung; Lee, Hwayoung; Park, Minkyung; Lee, Ahrim; Lee, Choongho; Lee, Kyeong [European Journal of Medicinal Chemistry, 2019, vol. 184]
[13]Current Patent Assignee: JOHN WAYNE CANCER INSTITUTE - WO2020/219718, 2020, A1 Location in patent: Page/Page column 43
[14]Current Patent Assignee: DONGGUK UNIVERSITY - KR102263733, 2021, B1 Location in patent: Paragraph 0255; 0267-0273
[15]Cao, Shengtian; Li, Jing; Lin, Runfeng; Wang, Xiaojun; Xu, Juan; Yang, Wen; Yang, Xinye; Zhang, Jiancun; Zhang, Zheng; Zuo, Yinglin [2021, vol. 12, # 7, p. 1222 - 1231]

10
[ 63909-58-0 ]
[ 79099-07-3 ]
[ 183951-17-9 ]

Yield	Reaction Conditions	Operation in experiment
91%	With potassium <i>tert</i>-butylate In tetrahydrofuran at 20℃; Cooling with ice;	7.2 Step 2: tert-butyl 4-(4-fluorobenzylidene)piperidine-1-carboxylate Step 2: tert-butyl 4-(4-fluorobenzylidene)piperidine-1-carboxylate[002131 To a mixture of tert-butyl 4-oxopiperidine-1-carboxylate (2.53 g, 12.70 mmol), diethyl 4-fluorobenzylphosphonate (3.91 g, 15.88 mmol) and THF (50 mL) was added a solution of potassium tert-butanolate (1.96 g, 17.47 mmol) in anhydrous THF (20 mL) dropwies at ice bath. After the addition, the mixture was stirred at it overnight. After the reaction was finished, the mixture was diluted with water (100 mL), and extracted with EtOAc (100 mL x 2). The combined organic phases were washed with water (100 mL x 2) and saturated brine (100 mL x 2), dried over anhydrous Na2SO4 (20 g), filtered and concentrated in vacuo to give the title compound as yellow oil (4.63 g, 91.0 %). The compound was characterized by the following spectroscopic data:MS(ESI, pos.ion)m/z: 236.2 (M+1-t-Bu); exact mass of C,7H22FN02: 291.16; and‘H NMR (400 MHz, CDC13) 6 7.20-7.08 (m, 2H), 7.04-6.94 (m, 2H), 6.31 (s, 1H), 3.55 -3.45 (m, 2H), 3.45-3.35 (m, 2H), 2.42 (t,J 5.6 Hz, 2H), 2.36-2.26 (m, 2H), 1.48 (s, 9H).
77%	Stage #1: diethyl (4-fluorobenzyl)phosphonate With 15-crown-5; sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: N-tert-butyloxycarbonylpiperidin-4-one In tetrahydrofuran at 20℃; for 22h;
51.6%	Stage #1: diethyl (4-fluorobenzyl)phosphonate With 15-crown-5; sodium hydride In tetrahydrofuran; water at 0 - 20℃; for 0.5h; Cooling with ice; Stage #2: N-tert-butyloxycarbonylpiperidin-4-one In tetrahydrofuran at 0 - 20℃; Cooling with ice;

48%	Stage #1: diethyl (4-fluorobenzyl)phosphonate With sodium hydride In N,N-dimethyl-formamide Stage #2: N-tert-butyloxycarbonylpiperidin-4-one
	In tetrahydrofuran; water	R.5.1 4-(4-Fluorobenzyl)piperidine hydrochloride 60% Sodium hydride (oily, 9.75 g) was added to a solution of diethyl 4-fluorobenzyl phosphonate (60.8 g) and 15-crown-5 (4 ml) in THF (400 ml) with stirring under ice cooling, and the mixture was stirred for 30 minutes at the same temperature. A solution of 1-tert-butoxycarbonyl-4-piperidone (42.0 g) in THF (150 ml) was dropwise added to the mixture with stirring under ice cooling, and the mixture was stirred for 22 hours at room temperature. Under ice cooling, water was added to the mixture and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated aqueous solutions of sodium bicarbonate and saturated brine in order. The organic phase was dried over magnesium sulfate (anhydrous) and concentrated under reduced pressure. The residue was subjected to column chromatography (silica gel 650 g, hexane/ethyl acetate=30/1→10/1). The objective fraction was concentrated under reduced pressure to give 1-tert-butoxycarbonyl-4-(4-fluorobenzylidene)piperidine (47.0 g). 1H NMR (CDCl3) δ 1.48 (9H, s), 2.32-2.44 (4H, m), 3.37-3.53 (4H, m), 6.31 (1H, s), 7.00-7.19 (4H, m)
	With sodium hydride In tetrahydrofuran at 20℃; for 24h; Cooling with ice;

Reference： [1]Current Patent Assignee: SHENZHEN DONGYANGGUANG INDUSTRIAL DEVELOPMENT CO LTD - WO2015/90232, 2015, A1 Location in patent: Paragraph 00213
[2]Imamura, Shinichi; Nishikawa, Youichi; Ichikawa, Takashi; Hattori, Taeko; Matsushita, Yoshihiro; Hashiguchi, Shohei; Kanzaki, Naoyuki; Iizawa, Yuji; Baba, Masanori; Sugihara, Yoshihiro [Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 2, p. 397 - 416]
[3]Cao, Shengtian; Li, Jing; Lin, Runfeng; Wang, Xiaojun; Xu, Juan; Yang, Wen; Yang, Xinye; Zhang, Jiancun; Zhang, Zheng; Zuo, Yinglin [2021, vol. 12, # 7, p. 1222 - 1231]
[4]Location in patent: scheme or table Mavunkel, Babu J.; Perumattam, John J.; Tan, Xuefei; Luedtke, Gregory R.; Lu, Qing; Lim, Don; Kizer, Darin; Dugar, Sundeep; Chakravarty, Sarvajit; Xu, Yong-jin; Jung, Joon; Liclican, Albert; Levy, Daniel E.; Tabora, Jocelyn [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 3, p. 1059 - 1062]
[5]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP1219605, 2002, A1
[6]Current Patent Assignee: ADEKA CORP.; TAISHO PHARMACEUTICAL HOLDINGS CO., LTD. - EP1207159, 2002, A1 Location in patent: Page 13

11
[ 63909-58-0 ]
4-(4-fluorobenzyl)piperidine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: NaH; 15-crown-5 / tetrahydrofuran / 0.5 h / 0 °C 1.2: 77 percent / tetrahydrofuran / 22 h / 20 °C 2.1: 84 percent / H₂; water / Pd-C / methanol / 5 h / 20 °C 3.1: 96 percent / HCl / ethyl acetate / 1 h / 20 °C
	Multi-step reaction with 3 steps 1.1: sodium hydride; 15-crown-5 / tetrahydrofuran; water / 0.5 h / 0 - 20 °C / Cooling with ice 1.2: 0 - 20 °C / Cooling with ice 2.1: palladium 10% on activated carbon / tetrahydrofuran; methanol / 20 °C / Inert atmosphere 3.1: hydrogenchloride / ethyl acetate / 20 °C

Reference： [1]Imamura, Shinichi; Nishikawa, Youichi; Ichikawa, Takashi; Hattori, Taeko; Matsushita, Yoshihiro; Hashiguchi, Shohei; Kanzaki, Naoyuki; Iizawa, Yuji; Baba, Masanori; Sugihara, Yoshihiro [Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 2, p. 397 - 416]
[2]Cao, Shengtian; Li, Jing; Lin, Runfeng; Wang, Xiaojun; Xu, Juan; Yang, Wen; Yang, Xinye; Zhang, Jiancun; Zhang, Zheng; Zuo, Yinglin [2021, vol. 12, # 7, p. 1222 - 1231]

12
[ 63909-58-0 ]
[ 276872-81-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: NaH; 15-crown-5 / tetrahydrofuran / 0.5 h / 0 °C 1.2: 77 percent / tetrahydrofuran / 22 h / 20 °C 2.1: 84 percent / H₂; water / Pd-C / methanol / 5 h / 20 °C
	Multi-step reaction with 2 steps 1.1: sodium hydride; 15-crown-5 / tetrahydrofuran; water / 0.5 h / 0 - 20 °C / Cooling with ice 1.2: 0 - 20 °C / Cooling with ice 2.1: palladium 10% on activated carbon / tetrahydrofuran; methanol / 20 °C / Inert atmosphere

Reference： [1]Imamura, Shinichi; Nishikawa, Youichi; Ichikawa, Takashi; Hattori, Taeko; Matsushita, Yoshihiro; Hashiguchi, Shohei; Kanzaki, Naoyuki; Iizawa, Yuji; Baba, Masanori; Sugihara, Yoshihiro [Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 2, p. 397 - 416]
[2]Cao, Shengtian; Li, Jing; Lin, Runfeng; Wang, Xiaojun; Xu, Juan; Yang, Wen; Yang, Xinye; Zhang, Jiancun; Zhang, Zheng; Zuo, Yinglin [2021, vol. 12, # 7, p. 1222 - 1231]

13
[ 63909-58-0 ]
[ 38693-94-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: NaOMe; 18/6-crown ether / dimethylformamide / 0.08 h / 20 °C 1.2: 80 percent / 18/6-crown ether / dimethylformamide / 6 h / 20 - 120 °C 2.1: 93 percent / pyridinium p-toluene sulfonate / methanol / Heating

Reference： [1]Lion, Cedric J.; Matthews, Charles S.; Stevens, Malcolm F. G.; Westwell, Andrew D. [Journal of Medicinal Chemistry, 2005, vol. 48, # 4, p. 1292 - 1295]

14
[ 63909-58-0 ]
[ 89122-67-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: NaOMe; 18/6-crown ether / dimethylformamide / 0.08 h / 20 °C 1.2: 89 percent / 18/6-crown ether / dimethylformamide / 6 h / 20 - 120 °C 2.1: 72 percent / pyridinium p-toluene sulfonate / methanol / Heating

Reference： [1]Lion, Cedric J.; Matthews, Charles S.; Stevens, Malcolm F. G.; Westwell, Andrew D. [Journal of Medicinal Chemistry, 2005, vol. 48, # 4, p. 1292 - 1295]

15
[ 63909-58-0 ]
[ 196520-14-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: NaOMe; 18/6-crown ether / dimethylformamide / 0.08 h / 20 °C 1.2: 92 percent / 18/6-crown ether / dimethylformamide / 6 h / 20 - 120 °C 2.1: 95 percent / pyridinium p-toluene sulfonate / methanol / Heating

Reference： [1]Lion, Cedric J.; Matthews, Charles S.; Stevens, Malcolm F. G.; Westwell, Andrew D. [Journal of Medicinal Chemistry, 2005, vol. 48, # 4, p. 1292 - 1295]

16
[ 63909-58-0 ]
[ 92822-02-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1,3-dimethyl-2-imidazolidinone; sodium hydride / 0.33 h / 20 °C 2: H₂ / Pd(OH)2/C / ethanol / 15 h / 20 °C / 2585.74 Torr

Reference： [1]McCauley, John A.; Theberge, Cory R.; Romano, Joseph J.; Billings, Susan B.; Anderson, Kenneth D.; Claremon, David A.; Freidinger, Roger M.; Bednar, Rodney A.; Mosser, Scott D.; Gaul, Stanley L.; Connolly, Thomas M.; Condra, Cindra L.; Xia, Menghang; Cunningham, Michael E.; Bednar, Bohumil; Stump, Gary L.; Lynch, Joseph J.; Macaulay, Alison; Wafford, Keith A.; Koblan, Kenneth S.; Liverton, Nigel J. [Journal of Medicinal Chemistry, 2004, vol. 47, # 8, p. 2089 - 2096]

17
[ 63909-58-0 ]
[ 1064778-36-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 1,3-dimethyl-2-imidazolidinone; sodium hydride / 0.33 h / 20 °C 2: H₂ / Pd(OH)2/C / ethanol / 15 h / 20 °C / 2585.74 Torr 3: diisopropylethylamine / dimethylformamide / 1 h / 20 °C

Reference： [1]McCauley, John A.; Theberge, Cory R.; Romano, Joseph J.; Billings, Susan B.; Anderson, Kenneth D.; Claremon, David A.; Freidinger, Roger M.; Bednar, Rodney A.; Mosser, Scott D.; Gaul, Stanley L.; Connolly, Thomas M.; Condra, Cindra L.; Xia, Menghang; Cunningham, Michael E.; Bednar, Bohumil; Stump, Gary L.; Lynch, Joseph J.; Macaulay, Alison; Wafford, Keith A.; Koblan, Kenneth S.; Liverton, Nigel J. [Journal of Medicinal Chemistry, 2004, vol. 47, # 8, p. 2089 - 2096]

18
[ 63909-58-0 ]
2-[4-(4-fluoro-benzyl)-piperidin-1-ylmethyl]-6-methoxy-1H-benzoimidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: 1,3-dimethyl-2-imidazolidinone; sodium hydride / 0.33 h / 20 °C 2.1: H₂ / Pd(OH)2/C / ethanol / 15 h / 20 °C / 2585.74 Torr 3.1: diisopropylethylamine / dimethylformamide / 1 h / 20 °C 4.1: aq. HCl / 1 h / 100 °C 5.1: 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride; 1-hydroxy-7-azabenzotriazole; triethylamine / dimethylformamide / 0.33 h / 20 °C 5.2: acetic acid / 0.25 h / 140 °C

Reference： [1]McCauley, John A.; Theberge, Cory R.; Romano, Joseph J.; Billings, Susan B.; Anderson, Kenneth D.; Claremon, David A.; Freidinger, Roger M.; Bednar, Rodney A.; Mosser, Scott D.; Gaul, Stanley L.; Connolly, Thomas M.; Condra, Cindra L.; Xia, Menghang; Cunningham, Michael E.; Bednar, Bohumil; Stump, Gary L.; Lynch, Joseph J.; Macaulay, Alison; Wafford, Keith A.; Koblan, Kenneth S.; Liverton, Nigel J. [Journal of Medicinal Chemistry, 2004, vol. 47, # 8, p. 2089 - 2096]

19
[ 63909-58-0 ]
2-[4-(4-fluoro-benzyl)-piperidin-1-ylmethyl]-3H-benzoimidazol-5-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: 1,3-dimethyl-2-imidazolidinone; sodium hydride / 0.33 h / 20 °C 2.1: H₂ / Pd(OH)2/C / ethanol / 15 h / 20 °C / 2585.74 Torr 3.1: diisopropylethylamine / dimethylformamide / 1 h / 20 °C 4.1: aq. HCl / 1 h / 100 °C 5.1: 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride; 1-hydroxy-7-azabenzotriazole; triethylamine / dimethylformamide / 0.33 h / 20 °C 5.2: acetic acid / 0.25 h / 140 °C 6.1: aq. HBr / 3 h / 100 °C

Reference： [1]McCauley, John A.; Theberge, Cory R.; Romano, Joseph J.; Billings, Susan B.; Anderson, Kenneth D.; Claremon, David A.; Freidinger, Roger M.; Bednar, Rodney A.; Mosser, Scott D.; Gaul, Stanley L.; Connolly, Thomas M.; Condra, Cindra L.; Xia, Menghang; Cunningham, Michael E.; Bednar, Bohumil; Stump, Gary L.; Lynch, Joseph J.; Macaulay, Alison; Wafford, Keith A.; Koblan, Kenneth S.; Liverton, Nigel J. [Journal of Medicinal Chemistry, 2004, vol. 47, # 8, p. 2089 - 2096]

20
[ 63909-58-0 ]
[4-(4-fluoro-benzyl)-piperidin-1-yl]-acetic acid; hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 1,3-dimethyl-2-imidazolidinone; sodium hydride / 0.33 h / 20 °C 2: H₂ / Pd(OH)2/C / ethanol / 15 h / 20 °C / 2585.74 Torr 3: diisopropylethylamine / dimethylformamide / 1 h / 20 °C 4: aq. HCl / 1 h / 100 °C

Reference： [1]McCauley, John A.; Theberge, Cory R.; Romano, Joseph J.; Billings, Susan B.; Anderson, Kenneth D.; Claremon, David A.; Freidinger, Roger M.; Bednar, Rodney A.; Mosser, Scott D.; Gaul, Stanley L.; Connolly, Thomas M.; Condra, Cindra L.; Xia, Menghang; Cunningham, Michael E.; Bednar, Bohumil; Stump, Gary L.; Lynch, Joseph J.; Macaulay, Alison; Wafford, Keith A.; Koblan, Kenneth S.; Liverton, Nigel J. [Journal of Medicinal Chemistry, 2004, vol. 47, # 8, p. 2089 - 2096]

21
[ 63909-58-0 ]
2-[4-(4-fluoro-phenyl)-5-oxo-3-thiophen-2-yl-2,5-dihydro-furan-2-carbonyl]-amino}-propionic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: BuLi / -78 °C 2.1: diethyl ether / 20 °C 3.1: LiCl / tetrahydrofuran / 0.08 h / 0 °C 3.2: Et₃N / tetrahydrofuran / 4 h / 20 °C

Reference： [1]Beck; Magnin-Lachaux; Herdtweck; Doemling [Organic letters, 2001, vol. 3, # 18, p. 2875 - 2878]

22
[ 63909-58-0 ]
2-{2-[(diethoxy-phosphoryl)-(4-fluoro-phenyl)-acetoxy]-3-oxo-3-thiophen-2-yl-propionylamino}-propionic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: BuLi / -78 °C 2: diethyl ether / 20 °C

Reference： [1]Beck; Magnin-Lachaux; Herdtweck; Doemling [Organic letters, 2001, vol. 3, # 18, p. 2875 - 2878]

23
[ 63909-58-0 ]
[ 73584-06-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1.) n-BuLi, HMDS, 2.) Cl₃C-CCl₃ / 1.) hexane, THF, -78 deg C -> 20 deg C; 20 deg C, 15 min, 2.) THF, -78 deg C, 15 min; -78 deg C -> 0 deg C 2: EtOLi / ethanol / 0.25 h / 0 °C
	Multi-step reaction with 3 steps 1: 1.) LiHMDS / 1.) THF, -78 deg C to 0 deg C, 2.) 20 deg C 2: hexachloroethane / tetrahydrofuran / -78 - 0 °C 3: 94 percent / 1M LiOH / H₂O / 0 °C

Reference： [1]Iorga, Bogdan; Eymery, Frederic; Savignac, Philippe [Tetrahedron, 1999, vol. 55, # 9, p. 2671 - 2686]
[2]Iorga, Bogdan; Eymery, Frederic; Savignac, Philippe [Tetrahedron Letters, 1998, vol. 39, # 22, p. 3693 - 3696]

24
[ 63909-58-0 ]
[ 209627-04-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1.) n-BuLi, HMDS, 2.) NFBS / 1.) hexane, THF, -78 deg C -> 20 deg C; 20 deg C, 15 min, 2.) THF, -90 deg C, 15 min; -90 deg C -> 0 deg C 2: LiOH, H₂O / 0.25 h / 0 °C
	Multi-step reaction with 3 steps 1: 1.) LiHMDS / 1.) THF, -78 deg C to 0 deg C, 2.) 20 deg C 2: N-fluorobenzenesulfonimide / tetrahydrofuran / -78 - 0 °C 3: 68 percent / 1M LiOH / H₂O / 0 °C

Reference： [1]Iorga, Bogdan; Eymery, Frederic; Savignac, Philippe [Tetrahedron, 1999, vol. 55, # 9, p. 2671 - 2686]
[2]Iorga, Bogdan; Eymery, Frederic; Savignac, Philippe [Tetrahedron Letters, 1998, vol. 39, # 22, p. 3693 - 3696]

25
[ 63909-58-0 ]
diethyl α-bromo-4-fluorobenzylphosphonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1.) n-BuLi, HMDS, 2.) BrCl₂C-CCl₂Br / 1.) hexane, THF, -78 deg C -> 20 deg C; 20 deg C, 15 min, 2.) THF, -78 deg C, 15 min; -78 deg C -> 0 deg C 2: EtOLi / ethanol / 0.25 h / 0 °C

Reference： [1]Iorga, Bogdan; Eymery, Frederic; Savignac, Philippe [Tetrahedron, 1999, vol. 55, # 9, p. 2671 - 2686]

26
[ 63909-58-0 ]
[ 209626-95-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1.) LiHMDS / 1.) THF, -78 deg C to 0 deg C, 2.) 20 deg C 2: N-fluorobenzenesulfonimide / tetrahydrofuran / -78 - 0 °C

Reference： [1]Iorga, Bogdan; Eymery, Frederic; Savignac, Philippe [Tetrahedron Letters, 1998, vol. 39, # 22, p. 3693 - 3696]

27
[ 63909-58-0 ]
[ 209627-01-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1.) LiHMDS / 1.) THF, -78 deg C to 0 deg C, 2.) 20 deg C 2: hexachloroethane / tetrahydrofuran / -78 - 0 °C

Reference： [1]Iorga, Bogdan; Eymery, Frederic; Savignac, Philippe [Tetrahedron Letters, 1998, vol. 39, # 22, p. 3693 - 3696]

28
[ 63909-58-0 ]
C₁₁H₁₄⁽²⁾H₂FO₃P [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1.) BuLi, diisopropylamine, 3.) D₂O / 1) THF, hexane, -78 deg C; 2) THF, hexane, 0 deg C, 30 min; 3) THF, hexane, room temperature 2: LiOD, D₂O, Na / tetrahydrofuran / 10 h / 20 °C

Reference： [1]Berte-Verrando, Sylvie; Nief, Francois; Patois, Carl; Savignac, Philippe [Journal of the Chemical Society. Perkin transactions I, 1994, # 7, p. 821 - 824]

29
[ 63909-58-0 ]
(3aR,7aR)-2-(4-Fluoro-benzyl)-1,3-dimethyl-octahydro-benzo[1,3,2]diazaphosphole 2-oxide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1) TMSBr, 2) oxalyl chloride, DMF / 1) room temperature, 2) CH₂Cl₂, room temperature 2: Et₃N / acetonitrile; benzene / 1) 0 deg C to room temperature, 2) room temperature

Reference： [1]Udayakumar, B. S.; Schuster, Gary B. [Journal of Organic Chemistry, 1993, vol. 58, # 15, p. 4165 - 4169]

30
[ 459-46-1 ]
[ 63909-58-0 ]

Yield	Reaction Conditions	Operation in experiment
	With triethyl phosphite	R.3.1 4-(4-Fluorobenzyl)piperidine Hydrochloride REFERENCE EXAMPLE 3-1 4-(4-Fluorobenzyl)piperidine Hydrochloride 4-fluorobenzyl bromide (100 g) and triethyl phosphite (120 ml) were mixed, and the mixture was stirred at 150° C., for 22 hours. The obtained reaction mixture was distilled under reduced pressure (bp 115-120° C./1.5 mmHg) to give diethyl 4-fluorobenzylphosphonate (125 g).
	With triethyl phosphite	R.5.1 4-(4-Fluorobenzyl)piperidine hydrochloride Reference Example 5-1 4-(4-Fluorobenzyl)piperidine hydrochloride 4-Fluorobenzylbromide (100 g) and triethyl phosphite (120 ml) were mixed and the mixture was stirred for 22 hours at 150°C. The obtained reaction mixture was distilled under reduced pressure (bp 115-120°C/1.5 mmHg) to give diethyl 4-fluorobenzyl phosphonate (125 g).

Reference： [1]Current Patent Assignee: ABBVIE INC - US6562978, 2003, B1
[2]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP1219605, 2002, A1

31
[ 33100-27-5 ]
[ 63909-58-0 ]
[ 144-55-8 ]
[ 85908-96-9 ]
[ 183951-17-9 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran	6 Synthesis of 4-(4-fluorobenzylidene)piperidine hydrochloride EXAMPLE 6 Synthesis of 4-(4-fluorobenzylidene)piperidine hydrochloride A solution of 59.78 g of N-t-butoxycarbonylpiperidone and 81.25 g of diethyl 4-fluorobenzylphosphonate in 150 ml of tetrahydrofuran was added dropwise to a suspension of 13.20 g of 60% sodium hydride (in oil) containing 1.65 g of 15-crown-5 ether in 650 ml of tetrahydrofuran which was cooled in an ice bath over 20 minutes. After 1 day of stirring at room temperature, saturated aqueous sodium bicarbonate was carefully added to the reaction mixture which was subsequently extracted with ethyl acetate. The extract was washed with saturated aqueous sodium bicarbonate and saturated brine and dried over anhydrous sodium sulfate, the drying agent was removed by filtration, and then the resulting filtrate was concentrated under reduced pressure and purified by a flash column chromatography (silica gel: Wako Gel C200 (manufactured by Wako Pure Chemical Industries), eluant: hexane-ethyl acetate=20.1) to obtain 55.23 g of N-t-butoxycarbonyl-4-(4-fluorobenzylidene)piperidine. The thus obtained oily product was crystallized after its overnight standing at room temperature. m.p. 69-70° C.

Reference： [1]Current Patent Assignee: ADEKA CORP.; TAISHO PHARMACEUTICAL HOLDINGS CO., LTD. - US6166033, 2000, A

32
[ 33100-27-5 ]
[ 63909-58-0 ]
[ 79099-07-3 ]
[ 144-55-8 ]
[ 183951-17-9 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran	13.1 Synthesis of 4-(4-fluorobenzylidene)piperidine hydrochloride (1) A solution of 59.78 g of N-t-butoxycarbonyl-4-piperidone and 81.25 g of diethyl 4-fluorobenzylphosphonate in 150 ml of tetrahydrofuran was added dropwise to a stirred suspension of 13.20 g of 60 % sodium hydride (in oil) containing 1.65 g of 15-crown-5 ether in 650 ml of tetrahydrofuran, under cooling on ice for 20 minutes. The mixture was stirred for one day at room temperature, and saturated aqueous sodium hydrogen carbonate was added carefully, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate and then with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate. The desiccant was removed by filtration, and the filtrate was concentrated under reduced pressure and purified by flash column chromatography (silica gel: Wako Gel C200, eluent: hexane/ethyl acetate = 20: 1) to give 55.23 g of N-t-butoxycarbonyl-4-(4-fluorobenzylidene)piperidine. The resulting oily substance was crystallized by allowing to stand overnight at room temperature. m.p. 69.0 - 70.0°C

Reference： [1]Current Patent Assignee: TAISHO PHARMACEUTICAL HOLDINGS CO., LTD.; ADEKA CORP. - EP816362, 1998, A1

33
[ 183951-17-9 ]
[ 33100-27-5 ]
[ 63909-58-0 ]
[ 144-55-8 ]
[ 85908-96-9 ]
4-(4-fluorobenzylidene)piperidine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride In tetrahydrofuran; 1,4-dioxane	8 Synthesis of 4-(4-fluorobenzylidene)piperidine hydrochloride EXAMPLE 8 Synthesis of 4-(4-fluorobenzylidene)piperidine hydrochloride To a stirred suspension of 13.20 g of 60% sodium hydride (in oil) containing 1.65 g of 15-crown-5 ether in 650 ml of tetrahydrofuran were added dropwise a solution of 59.78 g of N-t-butoxycarbonylpiperidone and 81.25 g of diethyl 4-fluorobenzylphosphonate in 150 ml of tetrahydrofuran under ice-cooling over 20 minutes. After stirring at room temperature for a day, a saturated aqueous sodium bicarbonate solution was added cautiously, followed by extracting with ethyl acetate. The extract was washed with a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution, successively, and dried over anhydrous sodium sulfate, followed by removal of the drying agent by filtration. The filtrate was concentrated under reduced pressure and purified by a flash column chromatography (silica gel: Wakogel C200 (manufactured by Wako Pure Chemicals), eluent; hexane-ethyl acetate =20:1) to give 55.23 g of N-t-butoxycarbonyl-4-(4-fluorobenzylidene)piperidine as an oil, which was then crystallized by allowing to stand at room temperature overnight. m.p. 69-70°C. To 55.00 g of N-t-butoxycarbonyl-4-(4-fluorobenzylidene)piperidine was added 475 ml of an ice-cooled solution of 4 N hydrogen chloride in dioxane, followed by stirring at room temperature for 2 hours. The reaction solution was concentrated under reduced pressure, and the resulting crystals were recrystallized from isopropanol to give 40.72 g of 4-(4-fluorobenzylidene)piperidine hydrochloride. m.p. 184-185.5° C.

Reference： [1]Current Patent Assignee: ADEKA CORP.; TAISHO PHARMACEUTICAL HOLDINGS CO., LTD. - US6291467, 2001, B1

34
[ 762-04-9 ]
[ 459-46-1 ]
[ 63909-58-0 ]

Yield	Reaction Conditions	Operation in experiment
98%	With water; palladium diacetate; N-ethyl-N,N-diisopropylamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In tetrahydrofuran for 4h; Inert atmosphere; Reflux;
96%	With tris(dibenzylideneacetone)dipalladium⁽⁰⁾ chloroform complex; N-ethyl-N,N-diisopropylamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In tetrahydrofuran for 4h; Reflux; Inert atmosphere;

Reference： [1]Location in patent: scheme or table Lavén, Gaston; Stawinski, Jacek [Synlett, 2009, # 2, p. 225 - 228]
[2]Location in patent: experimental part Laven, Gaston; Kalek, Marcin; Jezowska, Martina; Stawinski, Jacek [New Journal of Chemistry, 2010, vol. 34, # 5, p. 967 - 975]

35
[ 1152958-62-7 ]
[ 63909-58-0 ]
[ 1189134-75-5 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: diethyl (4-fluorobenzyl)phosphonate With sodium hydride In tetrahydrofuran at 5℃; for 0.25h; Stage #2: 4-(4-formyl-3,5-dimethyl-1H-pyrazol-1-yl)benzonitrile In tetrahydrofuran at 5 - 20℃;	9 Example 9 0 4-{4- [ (E) -2- (4-fluorophenyl) ethenylj -3, 5-dimethyl-lH-pyrazol- 1-yl }benzonitrile[ 0359] [0360] Sodium hydride (53.3 mg) was suspended in THF (10 mL) , and the mixture was cooled to 5°C. Diethyl (4- fluorobenzyl) phosphonate (328 mg) was added, and the mixture was stirred for 15 min. 4- (4-Formyl-3, 5-dimethyl-lH-pyrazol-l- yl) benzonitrile (200 mg) obtained in Reference Example 3 was added to the reaction mixture, and the mixture was further stirred at room temperature for 16 hr. The reaction mixture was diluted with ethyl acetate and aqueous sodium hydrogen carbonate solution. The organic layer was separated and dried over anhydrous magnesium sulfate, and the solvent was concentrated. The obtained residue was purified by column chromatography (ethyl acetate-hexane) and recrystallized from ethyl acetate-hexane to give the title compound (200 mg) as colorless crystals. 1H-NMR(CDCl3)B: 2.46 (3H, s) , 2.48 (3H, s) , 6.74 (IH, d) , 6.86 (IH, d), 6.99-7.12 (2H, in) , 7.39-7.50 (2H, m) , 7.57-7.66 (2H, m) , 7.71-7.84 (2H, m)

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2009/119880, 2009, A1 Location in patent: Page/Page column 185-186

36
[ 63909-58-0 ]
C₇H₆FK [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium <i>tert</i>-butylate In tetrahydrofuran at 20℃; for 1h;	4-[(E)-2-(4-Fluoro-phenyl)-vinyl]-pyridin-2-ol:To a solution of dieihyl-4-fI?iorobenzyl-phosphonatc (515 mg, 2.09 mmol) in THF ( 10.0 mL) was added potassium tert-buloxide (246 mg, 2.09 mmol). After stirring at 20 0C for 1 h, the mixture was treated with 2-hydroxypyridoaIdehyde (246 mg, 2.00 mmol), and allowed to stir for 3 h at 20 0C. The reaction mixture was quenched with water, and the aqueous phase was extracted with DCM, the combined organic phases were dried over MgSO4 and concentrated in vacuo. The crude oil was purified by column chromatography (DCM to 20%methanol in DCM) gave the desired product 4-[(L)-2-(4-fluoro-phenyO-vinyl]-pyridin-2-ol (32.0 mg, 7.5%, 5: 1 transxis) as white crystal. 1H NMR (400 MHz, CDCh) ?: 7.56 (m, 2H), 7.33 (m, I H), 7.26 (m, IH), 7.08 (m, 2H), 6.87 (m, IH), 6.64 (m, IH), 6.54 (m, IH); ESMS m/e: 216 (M+H)+.

Reference： [1]Current Patent Assignee: H. LUNDBECK A/S - WO2009/120655, 2009, A1 Location in patent: Page/Page column 35

37
[ 63909-58-0 ]
[ 77-78-1 ]
[ 1159205-41-0 ]

Yield	Reaction Conditions	Operation in experiment
36%	Stage #1: diethyl (4-fluorobenzyl)phosphonate With methylmagnesium chloride In tetrahydrofuran at 0 - 20℃; for 1h; Stage #2: dimethyl sulfate In tetrahydrofuran at 20℃; for 2.5h; Stage #3: With hydrogenchloride; water In tetrahydrofuran	17.a To a stirred solution of diethyl (4-fluoro-benzyl)phopshonate (5.3 g) in tetrahydrofuran (15 ml) at 0° C. was added dropwise a solution of methylmagnesium chloride (11.5 ml, 3 M in tetrahydrofuran) and the reaction mixture was then stirred at 0° C. for 30 min and then at room temperature for a further 30 min. After re-cooling to 0° C., a solution of dimethyl sulphate (2.25 ml) in tetrahydrofuran (5 ml) was added dropwise. The mixture was stirred at room temperature for 2.5 h and then the mixture was quenched by dropwise addition of aqueous hydrochloric acid (2N) followed by addition of aqueous hydrochloric acid (5N). The mixture was taken up in ethyl acetate and the phases separated. The organic layer was washed sequentially with water and with saturated brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (SiO2, heptane/EtOAc gradient) to yield a colourless oil, (2.00 g, 36%); MS (ISP): 261.1 ([M+H]+).

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2010/29589, 2010, A1 Location in patent: Page/Page column 33

38
[ 1030630-68-2 ]
[ 63909-58-0 ]
[ 1112364-34-7 ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium <i>tert</i>-butylate In tetrahydrofuran at 0 - 20℃; for 2h; Inert atmosphere;

Reference： [1]Location in patent: experimental part Yang, Zhiyong; Chi, Zhenguo; Yu, Tao; Zhang, Xiqi; Chen, Meina; Xu, Bingjia; Liu, Siwei; Zhang, Yi; Xu, Jiarui [Journal of Materials Chemistry, 2009, vol. 19, # 31, p. 5541 - 5546]

39
[ 29943-42-8 ]
[ 63909-58-0 ]
[ 1227082-80-5 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium <i>tert</i>-butylate In tetrahydrofuran	Q1 and Q2 (R7 = 4-F-PhenyI) will react in THF in the presence of KOtBu to give compound Q3 (R7 = 4-F-PhenyI) after work up and purification.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2010/56722, 2010, A1 Location in patent: Page/Page column 327

40
[ 63909-58-0 ]
[ 67-64-1 ]
[ 702-09-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium <i>tert</i>-butylate In tetrahydrofuran	U1 (R3 = R4 = Me) and U2 (R7 = 4-F-Phenyl) will react in THF in the presence of KOtBu to give compound U3 (R7 = 4-F-Phenyl, R3 = R4 = Me) after work up and purification.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2010/56722, 2010, A1 Location in patent: Page/Page column 341

41
[ 1237742-27-6 ]
[ 63909-58-0 ]
[ 1237742-28-7 ]

Yield	Reaction Conditions	Operation in experiment
	With 15-crown-5; sodium hydride In tetrahydrofuran at 0 - 25℃;

Reference： [1]Location in patent: scheme or table Ladduwahetty, Tammy; Gilligan, Myra; Humphries, Alexander; Merchant, Kevin J.; Fish, Rebecca; McAlister, George; Ivarsson, Magnus; Dominguez, Maria; O'Connor, Desmond; MacLeod, Angus M. [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 12, p. 3708 - 3712]

42
[ 1201-91-8 ]
[ 63909-58-0 ]
[ 1258962-97-8 ]

Yield	Reaction Conditions	Operation in experiment
42%	With sodium hydride In tetrahydrofuran; mineral oil for 5h; Reflux;

Reference： [1]Location in patent: experimental part Hong, Myeng Chan; Kim, Yun Kyung; Choi, Jae Yong; Yang, Si Qiang; Rhee, Hakjune; Ryu, Young Hoon; Choi, Tae Hyun; Cheon, Gi Jeong; An, Gwang Il; Kim, Hye Yun; Kim, Youngsoo; Kim, Dong Jin; Lee, Jun-Seok; Chang, Young-Tae; Lee, Kyo Chul [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 22, p. 7724 - 7730]

43
[ 63909-58-0 ]
[ 104-87-0 ]
[ 39769-27-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium ethanolate In N,N-dimethyl-formamide

Reference： [1]Location in patent: scheme or table Chen, Guanfan; Cao, Chenzhong [Journal of Physical Organic Chemistry, 2010, vol. 23, # 8, p. 776 - 782]

44
[ 63909-58-0 ]
[ 100-52-7 ]
1-fluoro-4-styrylbenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium ethanolate In N,N-dimethyl-formamide

Reference： [1]Location in patent: scheme or table Chen, Guanfan; Cao, Chenzhong [Journal of Physical Organic Chemistry, 2010, vol. 23, # 8, p. 776 - 782]

45
[ 1316643-93-2 ]
[ 63909-58-0 ]
[ 1316643-99-8 ]

Yield	Reaction Conditions	Operation in experiment
52%	Stage #1: diethyl (4-fluorobenzyl)phosphonate With n-butyllithium In tetrahydrofuran; hexane at -78 - -30℃; for 0.833333h; Inert atmosphere; Stage #2: (2S,3R,Z)-2-(tert-butyldimethylsilyloxy)-6-(tert-butyldiphenylsilyloxy)-3-fluorohex-4-enal In tetrahydrofuran; hexane at 20℃; for 3h; Inert atmosphere; optical yield given as %de; stereoselective reaction;

Reference： [1]Location in patent: experimental part Chen, Jun-Ling; Zheng, Feng; Huang, Yangen; Qing, Feng-Ling [Journal of Organic Chemistry, 2011, vol. 76, # 16, p. 6525 - 6533]

46
[ 1067-71-6 ]
[ 352-34-1 ]
[ 63909-58-0 ]

Yield	Reaction Conditions	Operation in experiment
85%	With [2,2]bipyridinyl; copper(II) acetate monohydrate; potassium carbonate In dimethyl sulfoxide at 110℃; for 40h; Inert atmosphere;

Reference： [1]Location in patent: experimental part Rout, Laxmidhar; Regati, Sridhar; Zhao, Cong-Gui [Advanced Synthesis and Catalysis, 2011, vol. 353, # 18, p. 3340 - 3346]

47
[ 210422-66-5 ]
[ 762-04-9 ]
[ 63909-58-0 ]

Yield	Reaction Conditions	Operation in experiment
92%	With copper(l) iodide; caesium carbonate In 1,2-dimethoxyethane at 80℃; for 2h; Inert atmosphere;
	With copper(l) iodide; caesium carbonate In 1,2-dimethoxyethane at 80℃; for 12h;

Reference： [1]Miao, Wenjun; Gao, Yuzhen; Li, Xueqin; Gao, Yuxing; Tang, Guo; Zhao, Yufen [Advanced Synthesis and Catalysis, 2012, vol. 354, # 14-15, p. 2659 - 2664]
[2]Ash, Jeffrey; Cordero, Paula; Huang, Hai; Kang, Jun Yong [Organic and Biomolecular Chemistry, 2021, vol. 19, # 27, p. 6007 - 6014]

48
[ 459-57-4 ]
[ 63909-58-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: methanol / 0.5 h / 20 °C 2: copper(l) iodide; caesium carbonate / 1,2-dimethoxyethane / 2 h / 80 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: methanol / 1 h 2: copper(l) iodide; caesium carbonate / 1,2-dimethoxyethane / 12 h / 80 °C

Reference： [1]Miao, Wenjun; Gao, Yuzhen; Li, Xueqin; Gao, Yuxing; Tang, Guo; Zhao, Yufen [Advanced Synthesis and Catalysis, 2012, vol. 354, # 14-15, p. 2659 - 2664]
[2]Ash, Jeffrey; Cordero, Paula; Huang, Hai; Kang, Jun Yong [Organic and Biomolecular Chemistry, 2021, vol. 19, # 27, p. 6007 - 6014]

49
[ 63909-58-0 ]
[ 100-52-7 ]
[ 718-25-2 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: diethyl (4-fluorobenzyl)phosphonate With sodium methylate In methanol; N,N-dimethyl-formamide Inert atmosphere; Stage #2: benzaldehyde at 0℃; Reflux; Inert atmosphere;	Preparation of (E)-stilbenes 10-13 and 16-22 via Horner-Wadsworth-Emmons reaction General procedure: A mixture of a suitable benzyl bromide (1 mmol) and excess triethylphosphite were stirred at 130 °C for 20 h. Removal of the remaining phosphite by vacuum distillation furnished the desired phosphonate as the residue. This intermediate was dissolved in 2 mL of dry DMF, contained in a flame-dried round-bottomed flask under a nitrogen atmosphere. Next, a solution of NaOMe (0.73 equiv) in methanol was added dropwise. The contents of the flask were cooled to 0 °C, upon which the aldehyde (0.67 equiv) was added. The resulting mixture was then successively stirred at room temperature for 1 h, heated to reflux temperature for another hour and left standing overnight. Afterward, a mixture of water and methanol (1:1) was added, which provided the desired stilbene as a precipitate. A second crop of crystals was harvested from the mother liquor.

Reference： [1]Roman, Bart I.; De Coen, Laurens M.; Mortier, Séverine Thérèse F.C.; De Ryck, Tine; Vanhoecke, Barbara W.A.; Katritzky, Alan R.; Bracke, Marc E.; Stevens, Christian V. [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 17, p. 5054 - 5063]

50
[ 63909-58-0 ]
[ 459-57-4 ]
(E)-1,2-di(4-fluorophenyl)ethene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: diethyl (4-fluorobenzyl)phosphonate With sodium methylate In methanol; N,N-dimethyl-formamide Inert atmosphere; Stage #2: 4-fluorobenzaldehyde at 0℃; Inert atmosphere; Reflux;	Preparation of (E)-stilbenes 10-13 and 16-22 via Horner-Wadsworth-Emmons reaction General procedure: A mixture of a suitable benzyl bromide (1 mmol) and excess triethylphosphite were stirred at 130 °C for 20 h. Removal of the remaining phosphite by vacuum distillation furnished the desired phosphonate as the residue. This intermediate was dissolved in 2 mL of dry DMF, contained in a flame-dried round-bottomed flask under a nitrogen atmosphere. Next, a solution of NaOMe (0.73 equiv) in methanol was added dropwise. The contents of the flask were cooled to 0 °C, upon which the aldehyde (0.67 equiv) was added. The resulting mixture was then successively stirred at room temperature for 1 h, heated to reflux temperature for another hour and left standing overnight. Afterward, a mixture of water and methanol (1:1) was added, which provided the desired stilbene as a precipitate. A second crop of crystals was harvested from the mother liquor.
	Stage #1: diethyl (4-fluorobenzyl)phosphonate With sodium methylate In methanol; N,N-dimethyl-formamide Inert atmosphere; Stage #2: 4-fluorobenzaldehyde In methanol; N,N-dimethyl-formamide at 0 - 20℃; Inert atmosphere; Reflux;	B.2 General procedure: [0383] Preparation of Stilbenes 90 and 91 Via Horner-Wadsworth-Emmons Reaction. [0384] A mixture of a suitable benzyl bromide (1 mmol) and excess triethyl phosphite are stirred at 130° C. for 20 h. Removal of the remaining phosphite by vacuum distillation furnishes the desired phosphonate as the residue. This intermediate is dissolved in 2 mL of dry dimethylformamide, contained in a flame-dried round-bottomed flask under a nitrogen atmosphere. Next, a solution of sodium methoxide (0.73 equiv.) in methanol is added dropwise. The contents of the flask is cooled to 0° C., upon which the aldehyde (0.67 equiv.) is added. The resulting mixture is then successively stirred at room temperature for 1 h, heated to reflux temperature for another hour and left standing overnight. [0385] Afterward, a mixture of water and methanol (1:1) is added, which provides the desired stilbene as a precipitate. A second crop of crystals can be harvested from the mother liquor.

Reference： [1]Roman, Bart I.; De Coen, Laurens M.; Mortier, Séverine Thérèse F.C.; De Ryck, Tine; Vanhoecke, Barbara W.A.; Katritzky, Alan R.; Bracke, Marc E.; Stevens, Christian V. [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 17, p. 5054 - 5063]
[2]Current Patent Assignee: GHENT UNIVERSITY - US2015/11620, 2015, A1 Location in patent: Paragraph 0383-0385

51
[ 63909-58-0 ]
[ 77123-58-1 ]
1-[(E)-2-(4-fluorophenyl)ethenyl]-2-[2-(trimethylsilyl)ethynyl]benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%	Stage #1: diethyl (4-fluorobenzyl)phosphonate With sodium hexamethyldisilazane In tetrahydrofuran at 0℃; for 0.166667h; Inert atmosphere; Stage #2: 2-[2-(trimethylsilyl)ethynyl]benzaldehyde In tetrahydrofuran at 0℃; for 16h; Inert atmosphere;

Reference： [1]Kinoshita, Hidenori; Hirai, Nobuyoshi; Miura, Katsukiyo [Journal of Organic Chemistry, 2014, vol. 79, # 17, p. 8171 - 8181]

52
[ 63909-58-0 ]
C₂₁H₁₃F₂N₃O₂*C₂HF₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: sodium methylate; 18-crown-6 ether / N,N-dimethyl-formamide / 0.25 h / Inert atmosphere 1.2: 1.5 h / 0 - 45 °C / Inert atmosphere 2.1: sodium hydroxide; tert-butylhypochlorite / propan-1-ol; water / 0.08 h / Inert atmosphere 2.2: 8 h / 20 °C / Inert atmosphere 3.1: triethylamine / Inert atmosphere 3.2: 95 °C / Inert atmosphere 4.1: potassium hydroxide / methanol / 1.5 h / 20 °C / Inert atmosphere 5.1: triethylamine / 1 h / Inert atmosphere 5.2: 16 h / 90 °C / Inert atmosphere

Reference： [1]Huang, Hong; Degnan, Andrew P.; Balakrishnan, Anand; Easton, Amy; Gulianello, Michael; Huang, Yanling; Matchett, Michele; Mattson, Gail; Miller, Regina; Santone, Kenneth S.; Senapati, Arun; Shields, Eric E.; Sivarao, Digavalli V.; Snyder, Lawrence B.; Westphal, Ryan; Whiterock, Valerie J.; Yang, Fukang; Bronson, Joanne J.; Macor, John E. [Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 17, p. 4165 - 4169]

53
[ 63909-58-0 ]
(4R,5R)-4-(5-bromopyridin-3-yl)-5-(4-fluorophenyl)oxazolidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: sodium methylate; 18-crown-6 ether / N,N-dimethyl-formamide / 0.25 h / Inert atmosphere 1.2: 1.5 h / 0 - 45 °C / Inert atmosphere 2.1: sodium hydroxide; tert-butylhypochlorite / propan-1-ol; water / 0.08 h / Inert atmosphere 2.2: 8 h / 20 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 0.5 h / -10 °C / Inert atmosphere 2.1: sodium hydroxide; tert-butylhypochlorite / propan-1-ol / 0.17 h / 20 °C / Inert atmosphere 2.2: 72 h / 0 - 20 °C / Inert atmosphere 2.3: 0 °C / Inert atmosphere

Reference： [1]Huang, Hong; Degnan, Andrew P.; Balakrishnan, Anand; Easton, Amy; Gulianello, Michael; Huang, Yanling; Matchett, Michele; Mattson, Gail; Miller, Regina; Santone, Kenneth S.; Senapati, Arun; Shields, Eric E.; Sivarao, Digavalli V.; Snyder, Lawrence B.; Westphal, Ryan; Whiterock, Valerie J.; Yang, Fukang; Bronson, Joanne J.; Macor, John E. [Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 17, p. 4165 - 4169]
[2]Degnan, Andrew P.; Maxwell, Darrell; Balakrishnan, Anand; Brown, Jeffrey M.; Easton, Amy; Gulianello, Michael; Hanumegowda, Umesh; Hill-Drzewi, Melissa; Miller, Regina; Santone, Kenneth S.; Senapati, Arun; Shields, Eric E.; Sivarao, Digavalli V.; Westphal, Ryan; Whiterock, Valerie J.; Zhuo, Xiaoliang; Bronson, Joanne J.; Macor, John E. [Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 24, p. 5871 - 5876]

54
[ 63909-58-0 ]
(4R,5R)-5-(4-fluorophenyl)-4-(5-((trimethylsilyl)ethynyl)pyridin-3-yl)oxazolidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: sodium methylate; 18-crown-6 ether / N,N-dimethyl-formamide / 0.25 h / Inert atmosphere 1.2: 1.5 h / 0 - 45 °C / Inert atmosphere 2.1: sodium hydroxide; tert-butylhypochlorite / propan-1-ol; water / 0.08 h / Inert atmosphere 2.2: 8 h / 20 °C / Inert atmosphere 3.1: triethylamine / Inert atmosphere 3.2: 95 °C / Inert atmosphere

Reference： [1]Huang, Hong; Degnan, Andrew P.; Balakrishnan, Anand; Easton, Amy; Gulianello, Michael; Huang, Yanling; Matchett, Michele; Mattson, Gail; Miller, Regina; Santone, Kenneth S.; Senapati, Arun; Shields, Eric E.; Sivarao, Digavalli V.; Snyder, Lawrence B.; Westphal, Ryan; Whiterock, Valerie J.; Yang, Fukang; Bronson, Joanne J.; Macor, John E. [Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 17, p. 4165 - 4169]

55
[ 63909-58-0 ]
(4R,5R)-4-(5-ethynylpyridin-3-yl)-5-(4-fluorophenyl)oxazolidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: sodium methylate; 18-crown-6 ether / N,N-dimethyl-formamide / 0.25 h / Inert atmosphere 1.2: 1.5 h / 0 - 45 °C / Inert atmosphere 2.1: sodium hydroxide; tert-butylhypochlorite / propan-1-ol; water / 0.08 h / Inert atmosphere 2.2: 8 h / 20 °C / Inert atmosphere 3.1: triethylamine / Inert atmosphere 3.2: 95 °C / Inert atmosphere 4.1: potassium hydroxide / methanol / 1.5 h / 20 °C / Inert atmosphere

Reference： [1]Huang, Hong; Degnan, Andrew P.; Balakrishnan, Anand; Easton, Amy; Gulianello, Michael; Huang, Yanling; Matchett, Michele; Mattson, Gail; Miller, Regina; Santone, Kenneth S.; Senapati, Arun; Shields, Eric E.; Sivarao, Digavalli V.; Snyder, Lawrence B.; Westphal, Ryan; Whiterock, Valerie J.; Yang, Fukang; Bronson, Joanne J.; Macor, John E. [Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 17, p. 4165 - 4169]

56
[ 113118-81-3 ]
[ 63909-58-0 ]
(E)-3-bromo-5-(4-fluorostyryl)pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	Stage #1: diethyl (4-fluorobenzyl)phosphonate With 18-crown-6 ether; sodium methylate In N,N-dimethyl-formamide for 0.25h; Inert atmosphere; Stage #2: 5-bromopyridine-3-carbaldehyde In N,N-dimethyl-formamide at 0 - 45℃; for 1.5h; Inert atmosphere;	(E)-3-Bromo-5-(4-fluorostyryl)pyridine To a solution of diethyl 4-fluorobenzylphosphonate (25 g, 102mmol) in DMF (225 mL, 2906 mmol) was added sodium methoxide (10.97 g, 203 mmol)and 18-crown-6 (10.74 g, 40.6 mmol).After stirring for 15 min, the reaction was cooled to 0°C and treatedwith 5-bromonicotinaldehyde (18.89 g,102 mmol) as a solid in two portions over a couple of min. The ice bath was removed and the reactionstirred at room temperature for 1 h. Thereaction was warmed to 45°C and held at that temperature for 30 min. The reaction was cooled to room temperatureand poured into water (1000 mL) with vigorous stirring. The resulting suspension was extracted withether (ca. 700 mL), washed with water(3X), then brine, dried over MgSO4, and concentrated. The resulting solid was scraped into a beakerand triturated with a minimum of ethanol ~50 mL and placed in the freezer overthe weekend. The resulting solid was brokenup with a spatula and collected by filtration, and rinsed with a minimum ofcold ethanol to give 12.7 g (45%) as a white crystalline solid. 1H-NMR (CDCl3, 500 MHz) δ 8.62 (s, 1H), 8.56 (s, 1H), 7.97 (s, 1H), 7.50 (m, 2H), 7.10 (m,3H), 8.93 (m, 1H). Mass spec.: 277.78/279.72 (MH)+.

Reference： [1]Huang, Hong; Degnan, Andrew P.; Balakrishnan, Anand; Easton, Amy; Gulianello, Michael; Huang, Yanling; Matchett, Michele; Mattson, Gail; Miller, Regina; Santone, Kenneth S.; Senapati, Arun; Shields, Eric E.; Sivarao, Digavalli V.; Snyder, Lawrence B.; Westphal, Ryan; Whiterock, Valerie J.; Yang, Fukang; Bronson, Joanne J.; Macor, John E. [Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 17, p. 4165 - 4169]

57
[ 113118-81-3 ]
[ 63909-58-0 ]
C₁₃H₉BrFN [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium <i>tert</i>-butylate In tetrahydrofuran at -10℃; for 0.5h; Inert atmosphere;	(E)-3-Bromo-5-(2,3-dichlorostyryl)pyridine General procedure: To a solution 5-bromonicotinaldehyde (0.866 g, 4.65 mmol) and diethyl (2,3-dichlorobenzyl)phosphonate (1.317 g, 4.43 mmol) in THF (21 ml) at -10 °C (ice/acetone) was added potassium tert-butoxide (1M in THF, 5.1 ml, 5.1 mmol) dropwise. After 10 min, LC/MS showed clean, complete consumption of SM to give product. The reaction was allowed to stir a total of 30 min, then concentrated on the rotovap (bath temp = 20 °C). The resulting residue was suspended in water then dissolved in EtOAc. The layers were separated. The organics were washed with water, then brine, dried over MgSO4, filtered, and concentrated to give the crude product. The product was transferred to a small beaker and agitated under n-hexane (4 mL) and the organics decanted. The solid was again agitated under n-hexane (4 mL). The solid was collected in a buchner funnel and rinsed with n-hexane (2 mL) and air dried to give 1.26 g (78%) as a tan solid.

Reference： [1]Degnan, Andrew P.; Maxwell, Darrell; Balakrishnan, Anand; Brown, Jeffrey M.; Easton, Amy; Gulianello, Michael; Hanumegowda, Umesh; Hill-Drzewi, Melissa; Miller, Regina; Santone, Kenneth S.; Senapati, Arun; Shields, Eric E.; Sivarao, Digavalli V.; Westphal, Ryan; Whiterock, Valerie J.; Zhuo, Xiaoliang; Bronson, Joanne J.; Macor, John E. [Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 24, p. 5871 - 5876]

58
[ 63909-58-0 ]
(4R,5R)-4-(5-((3,3-difluorocyclobutyl)ethynyl)pyridin-3-yl)-5-(4-fluorophenyl)oxazolidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 0.5 h / -10 °C / Inert atmosphere 2.1: sodium hydroxide; tert-butylhypochlorite / propan-1-ol / 0.17 h / 20 °C / Inert atmosphere 2.2: 72 h / 0 - 20 °C / Inert atmosphere 2.3: 0 °C / Inert atmosphere 3.1: triphenylphosphine; copper(l) iodide; bis-triphenylphosphine-palladium(II) chloride; triethylamine / pentane / 16 h / 80 °C / Inert atmosphere; Sealed tube

Reference： [1]Degnan, Andrew P.; Maxwell, Darrell; Balakrishnan, Anand; Brown, Jeffrey M.; Easton, Amy; Gulianello, Michael; Hanumegowda, Umesh; Hill-Drzewi, Melissa; Miller, Regina; Santone, Kenneth S.; Senapati, Arun; Shields, Eric E.; Sivarao, Digavalli V.; Westphal, Ryan; Whiterock, Valerie J.; Zhuo, Xiaoliang; Bronson, Joanne J.; Macor, John E. [Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 24, p. 5871 - 5876]

59
[ 63909-58-0 ]
C₁₈H₁₆O₅ [ No CAS ]
C₂₅H₂₁FO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With sodium hydride In tetrahydrofuran at 120℃; for 0.5h; Microwave irradiation;

Reference： [1]Vo, Duc Duy; Elofsson, Mikael [Advanced Synthesis and Catalysis, 2016, vol. 358, # 24, p. 4085 - 4092]

60
[ 63909-58-0 ]
3-(3,5-dimethoxyphenyl)-6-methoxy-2-(4-methoxyphenyl)benzofuran-4-carbaldehyde [ No CAS ]
C₃₂H₂₇FO₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With sodium hydride In tetrahydrofuran at 120℃; for 0.5h; Microwave irradiation;

Reference： [1]Vo, Duc Duy; Elofsson, Mikael [Advanced Synthesis and Catalysis, 2016, vol. 358, # 24, p. 4085 - 4092]

61
[ 63909-58-0 ]
[ 6630-33-7 ]
(E)-1-bromo-2-(4-fluorostyryl)benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%	Stage #1: diethyl (4-fluorobenzyl)phosphonate With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: ortho-bromobenzaldehyde In tetrahydrofuran at 0 - 20℃;

Reference： [1]McAtee, Christopher C.; Riehl, Paul S.; Schindler, Corinna S. [Journal of the American Chemical Society, 2017, vol. 139, # 8, p. 2960 - 2963]

62
[ 63909-58-0 ]
[ 86-51-1 ]
(E)-1-(4-fluorostyryl)-2,3-dimethoxybenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: diethyl (4-fluorobenzyl)phosphonate With sodium hydride In tetrahydrofuran at 0 - 5℃; for 0.5h; Stage #2: 2,3-dimethyoxybenzaldehyde In tetrahydrofuran at 0 - 20℃; for 20h;	5.2.2. General procedure for synthesis of stilbenes General procedure: The appropriately substituted phosphonate ester (10 mmol) was dissolved in dry tetrahydrofuran (20 ml) and stirred at 0-5 °C. Sodium hydride (25 mmol) was added to the solution slowly and after thirty minutes the appropriate freshly distilled aldehyde(10 mmol) in tetrahydrofuran (30 ml) was added dropwise. The mixture was allowed to stir at room temperature overnight. In order to increase the yield, compounds 35, 37 and 40 were heated under reflux for 3-4 h. The mixture was cooled and quenched with ice water (10 ml) and poured onto ice. Dilute hydrochloric acid(1 M) was added until acidic and the solution was extracted with ethyl acetate (4 50 ml). The combined organic layers were washed with saturated salt and dried over magnesium sulfate. Filtration and evaporation of the ethyl acetate afforded crude stilbene products as oils or solids. The solids were crystallized from 95% ethanol to afford crystalline stilbenes. The oils were chromatographed on silica gel using methylene chloride to give pure products.

Reference： [1]Deck, Lorraine M.; Whalen, Lisa J.; Hunsaker, Lucy A.; Royer, Robert E.; Vander Jagt, David L. [Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 4, p. 1423 - 1430]

63
[ 63909-58-0 ]
[ 93-02-7 ]
(E)-2-(4-fluorostyryl)-1,4-dimethoxybenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	Stage #1: diethyl (4-fluorobenzyl)phosphonate With sodium hydride In tetrahydrofuran at 0 - 5℃; for 0.5h; Stage #2: 2,5-dimethoxybenzaldehyde In tetrahydrofuran at 0 - 20℃; for 20h;	5.2.2. General procedure for synthesis of stilbenes General procedure: The appropriately substituted phosphonate ester (10 mmol) was dissolved in dry tetrahydrofuran (20 ml) and stirred at 0-5 °C. Sodium hydride (25 mmol) was added to the solution slowly and after thirty minutes the appropriate freshly distilled aldehyde(10 mmol) in tetrahydrofuran (30 ml) was added dropwise. The mixture was allowed to stir at room temperature overnight. In order to increase the yield, compounds 35, 37 and 40 were heated under reflux for 3-4 h. The mixture was cooled and quenched with ice water (10 ml) and poured onto ice. Dilute hydrochloric acid(1 M) was added until acidic and the solution was extracted with ethyl acetate (4 50 ml). The combined organic layers were washed with saturated salt and dried over magnesium sulfate. Filtration and evaporation of the ethyl acetate afforded crude stilbene products as oils or solids. The solids were crystallized from 95% ethanol to afford crystalline stilbenes. The oils were chromatographed on silica gel using methylene chloride to give pure products.

Reference： [1]Deck, Lorraine M.; Whalen, Lisa J.; Hunsaker, Lucy A.; Royer, Robert E.; Vander Jagt, David L. [Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 4, p. 1423 - 1430]

64
[ 2646-90-4 ]
[ 63909-58-0 ]
(E)-1,4-difluoro-2-(4-fluorostyryl)benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	Stage #1: diethyl (4-fluorobenzyl)phosphonate With sodium hydride In tetrahydrofuran at 0 - 5℃; for 0.5h; Stage #2: 2,5-difluorobenzaldehyde In tetrahydrofuran at 0 - 20℃; for 20h;	5.2.2. General procedure for synthesis of stilbenes General procedure: The appropriately substituted phosphonate ester (10 mmol) was dissolved in dry tetrahydrofuran (20 ml) and stirred at 0-5 °C. Sodium hydride (25 mmol) was added to the solution slowly and after thirty minutes the appropriate freshly distilled aldehyde(10 mmol) in tetrahydrofuran (30 ml) was added dropwise. The mixture was allowed to stir at room temperature overnight. In order to increase the yield, compounds 35, 37 and 40 were heated under reflux for 3-4 h. The mixture was cooled and quenched with ice water (10 ml) and poured onto ice. Dilute hydrochloric acid(1 M) was added until acidic and the solution was extracted with ethyl acetate (4 50 ml). The combined organic layers were washed with saturated salt and dried over magnesium sulfate. Filtration and evaporation of the ethyl acetate afforded crude stilbene products as oils or solids. The solids were crystallized from 95% ethanol to afford crystalline stilbenes. The oils were chromatographed on silica gel using methylene chloride to give pure products.

Reference： [1]Deck, Lorraine M.; Whalen, Lisa J.; Hunsaker, Lucy A.; Royer, Robert E.; Vander Jagt, David L. [Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 4, p. 1423 - 1430]

65
[ 122-52-1 ]
[ 63909-58-0 ]

Yield	Reaction Conditions	Operation in experiment
	In neat (no solvent) at 130℃; for 20h;	5.2.1. General procedure for synthesis of phosphonate esters General procedure: Benzyl chloride or benzyl bromide derivatives (1 eq) were added to triethyl phosphite (1.5 eq) and heated to 130 °C for 20 h. After cooling, the resulting crude product was distilled in vacuo to remove excess triethyl phosphite and ethyl chloride or ethyl bromide. Purification by filtration through a pad of silica gel (70% ethyl acetate/30% hexanes) gave the phosphonate ester products as colorless oils.
	at 140℃; for 12h;

Reference： [1]Deck, Lorraine M.; Whalen, Lisa J.; Hunsaker, Lucy A.; Royer, Robert E.; Vander Jagt, David L. [Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 4, p. 1423 - 1430]
[2]Fu, Zhicheng; Sun, Simin; Yang, Anjian; Sun, Fang; Xu, Jiaxi [Chemical Communications, 2019, vol. 55, # 87, p. 13124 - 13127]

66
[ 459-56-3 ]
[ 122-52-1 ]
[ 63909-58-0 ]

Yield	Reaction Conditions	Operation in experiment
81%	at 120℃; for 24h; Inert atmosphere;	2 Example 2 Triethyl phosphite and 4-fluorobenzyl alcohol were used to prepare diethyl 4-fluorobenzylidene phosphonate To a 20 mL tubular reactor was added 4-fluorobenzyl alcohol (63.0 mg, 0.50 mmol)(3.8 mg, 0.01 mmol, 2 mol%), protected by vacuum nitrogen and then heated to 120 ° C under solvent-free conditions 24h TLC to monitor the reaction is complete, the product was purified by column chromatography, separation yield 81%
81%	With tetra-(n-butyl)ammonium iodide In neat (no solvent) at 125℃; for 24h; Inert atmosphere; Schlenk technique; Sealed tube; Green chemistry;

Reference： [1]Current Patent Assignee: WENZHOU UNIVERSITY - CN106543221, 2017, A Location in patent: Paragraph 0026; 0027; 0028; 0029
[2]Ma, Xiantao; Xu, Qing; Li, Huan; Su, Chenliang; Yu, Lei; Zhang, Xu; Cao, Hongen; Han, Li-Biao [Green Chemistry, 2018, vol. 20, # 15, p. 3408 - 3413]

67
[ 63909-58-0 ]
[ 6287-38-3 ]
3,4-dichloro-4’-fluoro-stilbene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With sodium hydroxide at 40℃; for 1h;	11 A batch of stilbene type compound was prepared by using the following reaction conditions in substantially the same manner as in Example 2, and the reaction conditions and the results are shown in Table 1.

Reference： [1]Current Patent Assignee: SOUTHEAST UNIVERSITY - CN104591959, 2016, B Location in patent: Paragraph 0074-0080

68
[ 63909-58-0 ]
[ 122-85-0 ]
4-chloro-4’-acetylamino-stilbene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With sodium hydroxide at 35℃; for 4h;	12 A batch of stilbene type compound was prepared by using the following reaction conditions in substantially the same manner as in Example 2, and the reaction conditions and the results are shown in Table 1.

Reference： [1]Current Patent Assignee: SOUTHEAST UNIVERSITY - CN104591959, 2016, B Location in patent: Paragraph 0074-0080

69
[ 63909-58-0 ]
[ 5257-24-9 ]
(E)-2-(4-fluorostyryl)-3-methyl-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	Stage #1: diethyl (4-fluorobenzyl)phosphonate With sodium hexamethyldisilazane In tetrahydrofuran at -78 - 20℃; for 0.5h; Stage #2: 2-formyl-3-methylindole In tetrahydrofuran at -50 - 20℃; for 0.75h;

Reference： [1]Pirovano, Valentina; Borri, Micol; Abbiati, Giorgio; Rizzato, Silvia; Rossi, Elisabetta [Advanced Synthesis and Catalysis, 2017, vol. 359, # 11, p. 1912 - 1918]

70
[ 63909-58-0 ]
ethyl (E)-2-(4-fluorostyryl)-3-methyl-1H-indole-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: sodium hexamethyldisilazane / tetrahydrofuran / 0.5 h / -78 - 20 °C 1.2: 0.75 h / -50 - 20 °C 2.1: n-butyllithium / tetrahydrofuran; hexane / 0.25 h / -78 °C 2.2: -78 - 20 °C

Reference： [1]Pirovano, Valentina; Borri, Micol; Abbiati, Giorgio; Rizzato, Silvia; Rossi, Elisabetta [Advanced Synthesis and Catalysis, 2017, vol. 359, # 11, p. 1912 - 1918]

71
[ 63909-58-0 ]
[ 99-91-2 ]
C₁₅H₁₂ClF [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride In N,N-dimethyl-formamide

Reference： [1]Zhang, Yanxiu; Cao, Chao-Tun; Zhang, Jingyuan; Cao, Chenzhong [Journal of Physical Organic Chemistry, 2017, vol. 30, # 12]

72
[ 63909-58-0 ]
(E)-1,2-di(4-fluorophenyl)ethene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: diethyl (4-fluorobenzyl)phosphonate With sodium t-butanolate In N,N-dimethyl-formamide at 25℃; for 0.0833333h; Inert atmosphere; Stage #2: With oxygen In N,N-dimethyl-formamide at 25℃; for 8h; stereoselective reaction;

Reference： [1]Huang, Tianzeng; Chen, Tieqiao; Han, Li-Biao [Journal of Organic Chemistry, 2018, vol. 83, # 5, p. 2959 - 2965]

73
[ 63909-58-0 ]
[ 345-92-6 ]
[ 798-59-4 ]

Yield	Reaction Conditions	Operation in experiment
70%	With potassium <i>tert</i>-butylate In tetrahydrofuran at 0 - 20℃; for 12.5h; Inert atmosphere;	1.2 (2) Synthesis of target product Example 1 4,4'-difluorobenzophenone (0.502 g, 0.002 mol) was added to a 100 mL three-neck round bottom flask.Diethyl 4-fluorophenylphosphonate (0.456 g, 0.002 mol) and dry THF solvent (30 mL).Stir under argon atmosphere and cool to 0 °C with ice bath.Potassium tert-butoxide (0.224 g, 0.002 mol) was added.After maintaining the ice bath for 0.5 h, the reaction was allowed to continue to room temperature for 12 h.At the end of the reaction, the reaction solution was poured into ethanol.A white precipitate precipitated and suction filtered to give a white solid.The white solid was collected and dissolved in dichloromethane.Wash three times with brine and collect the organic phase.Drying was carried out by adding anhydrous MgSO 4 and the solvent was removed by rotary evaporator.The obtained crude product was recrystallized from ethanol to give a white powder (0.5 g, yield: 70%).

Reference： [1]Current Patent Assignee: SUN YAT-SEN UNIVERSITY (CHINA) - CN108424346, 2018, A Location in patent: Paragraph 0030; 0034-0036

74
[ 63909-58-0 ]
4-benzyl-5-((tert-butyldimethylsilyl)oxy)-4-methylhexanal [ No CAS ]
C₂₇H₃₉FOSi [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: diethyl (4-fluorobenzyl)phosphonate With sodium hydride In tetrahydrofuran at 0 - 20℃; for 1h; Stage #2: 4-benzyl-5-((tert-butyldimethylsilyl)oxy)-4-methylhexanal In tetrahydrofuran at 0 - 20℃;

Reference： [1]Albright, Haley; Riehl, Paul S.; McAtee, Christopher C.; Reid, Jolene P.; Ludwig, Jacob R.; Karp, Lindsey A.; Zimmerman, Paul M.; Sigman, Matthew S.; Schindler, Corinna S. [Journal of the American Chemical Society, 2019, vol. 141, # 4, p. 1690 - 1700]

75
[ 63909-58-0 ]
[ 73365-02-3 ]
tert-butyl (R,E)-2-(4-fluorostyryl)pyrrolidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%		A solution of lithium bis(trimethylsilyl)amide (1 .0 M in THF, 78 mL, 78 mmol) was added dropwise to a solution of diethyl (4-fluorobenzyl)phosphonate (19.5 g, 79 mmol) in THF (100 ml.) at 0 C. Stirred at 0 C for 20 min, then added a solution of (R)-tert-butyl 2- formylpyrrolidine-1 -carboxylate (15 g, 75 mmol) in THF (40 mL) dropwise. The reaction mixture was stirred 0 C for 1 h and then slowly warmed to RT over 1 h and then stirred for an additional 2 h at RT. The reaction was quenched with water and extracted with EtOAc (twice). The combined organic extracts were washed with brine, dried over Na2S04, filtered and concentrated. Silica gel column chromatography (EtOAc/heptane) provided tert-butyl (R,E)-2-(4- fluorostyryl)pyrrolidine-1 -carboxylate (1 1 .65 g, colorless oil) in 53% yield. MS m/z 236.3 (M- tBu+H).

Reference： [1]Patent: WO2019/166950,2019,A1 .Location in patent: Paragraph 00128

76
[ 31558-40-4 ]
[ 63909-58-0 ]
(E)-2-bromo-5-(4-fluorostyryl)-1,3-dimethoxybenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
34%	Stage #1: diethyl (4-fluorobenzyl)phosphonate With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.5h; Inert atmosphere; Stage #2: 4-bromo-3,5-dimethoxybenzaldehyde In tetrahydrofuran; mineral oil at 20℃; for 12h; Inert atmosphere;	General Procedure for the Synthesis of 15a-f. General procedure: To a solution of aryl phosphonate (1.2 equiv) in THF at 0 °C under Ar atmosphere, NaH(60% dispersion in mineral oil, 2.0 equiv) was slowly added, and the reaction was stirred for30 min. A solution of corresponding benzaldehyde (1.0 equiv) in THF was added dropwiseand the resulting reaction mixture was stirred at rt for 12 h. The reaction was monitored byTLC. After completion of the reaction, the mixture was cooled to 0 °C and excess NaH wasquenched with water. The reaction mixture was poured on ice, followed by the addition of 2.0N HCl till pH 6 was obtained, and the product was extracted with EtOAc. The combinedorganic layers were washed with brine, dried over MgSO4, filtered, and concentrated invacuo. Purification by Flash Colum Chromatography (FCC) afforded the desired (E)-stilbene.
	With sodium hydride In tetrahydrofuran at 20℃; for 12h;

Reference： [1]Harmalkar, Dipesh S.; Lee, Sung-Jin; Lu, Qili; Kim, Mi Il; Park, Jaehyung; Lee, Hwayoung; Park, Minkyung; Lee, Ahrim; Lee, Choongho; Lee, Kyeong [European Journal of Medicinal Chemistry, 2019, vol. 184]
[2]Current Patent Assignee: DONGGUK UNIVERSITY - KR102263733, 2021, B1 Location in patent: Paragraph 0255; 0267-0270; 0274

77
[ 63909-58-0 ]
ethyl hydrogen (4-fluorobenzyl)phosphonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	Stage #1: diethyl (4-fluorobenzyl)phosphonate With pyridine; trifluoromethylsulfonic anhydride In dichloromethane for 0.166667h; Stage #2: With water In dichloromethane for 1h; Stage #3: With sodium hydroxide In diethyl ether for 0.5h;
	With sodium hydroxide In ethanol at 85℃; for 12h;

Reference： [1]Ash, Jeffrey; Cordero, Paula; Huang, Hai; Kang, Jun Yong [Organic and Biomolecular Chemistry, 2021, vol. 19, # 27, p. 6007 - 6014]
[2]Fu, Zhicheng; Sun, Simin; Yang, Anjian; Sun, Fang; Xu, Jiaxi [Chemical Communications, 2019, vol. 55, # 87, p. 13124 - 13127]

78
[ 63909-58-0 ]
rac-(2R,3R,4R)-2-ethoxy-3-(4-fluorophenyl)-4,6-diphenyl-3,4-dihydro-1,2-oxaphosphinine 2-oxide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: sodium hydroxide / ethanol / 12 h / 85 °C 2: thionyl chloride / 12 h / 80 °C / Inert atmosphere 3: lithium hexamethyldisilazane / tetrahydrofuran / 12 h / -78 - 20 °C / Molecular sieve

Reference： [1]Fu, Zhicheng; Sun, Simin; Yang, Anjian; Sun, Fang; Xu, Jiaxi [Chemical Communications, 2019, vol. 55, # 87, p. 13124 - 13127]

79
[ 63909-58-0 ]
C₉H₁₁ClFO₂P [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium hydroxide / ethanol / 12 h / 85 °C 2: thionyl chloride / 12 h / 80 °C / Inert atmosphere

Reference： [1]Fu, Zhicheng; Sun, Simin; Yang, Anjian; Sun, Fang; Xu, Jiaxi [Chemical Communications, 2019, vol. 55, # 87, p. 13124 - 13127]

80
[ 63909-58-0 ]
(R*)-1-((S*)-(4-fluorophenyl)(2,4,6-trimethoxyphenyl)methyl)-2-phenyl-1H-indene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: sodium hexamethyldisilazane / hexane; tetrahydrofuran / 0.5 h / -78 - 20 °C 1.2: 20 °C 2.1: [Au(1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene)(NTf₂)] / dichloromethane / 20 °C

Reference： [1]Virumbrales, Cintia; Solas, Marta; Suárez-Pantiga, Samuel; Fernández-Rodríguez, Manuel A.; Marín-Luna, Marta; López, Carlos Silva; Sanz, Roberto [Organic and Biomolecular Chemistry, 2019, vol. 17, # 46, p. 9924 - 9932]

81
[ 63909-58-0 ]
(R*)-1-((S*)-(4-fluorophenyl)(methoxy)methyl)-2-phenyl-1H-indene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: sodium hexamethyldisilazane / hexane; tetrahydrofuran / 0.5 h / -78 - 20 °C 1.2: 20 °C 2.1: [Au(1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene)(NTf₂)] / dichloromethane / 1 h / 20 °C

Reference： [1]Virumbrales, Cintia; Solas, Marta; Suárez-Pantiga, Samuel; Fernández-Rodríguez, Manuel A.; Marín-Luna, Marta; López, Carlos Silva; Sanz, Roberto [Organic and Biomolecular Chemistry, 2019, vol. 17, # 46, p. 9924 - 9932]

82
[ 63909-58-0 ]
(S*)-(4-fluorophenyl)((R*)-2-phenyl-1H-inden-1-yl)methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: sodium hexamethyldisilazane / hexane; tetrahydrofuran / 0.5 h / -78 - 20 °C 1.2: 20 °C 2.1: [Au(1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene)(NTf₂)]; water / 1,4-dioxane; dichloromethane / 16 h / 20 °C

Reference： [1]Virumbrales, Cintia; Solas, Marta; Suárez-Pantiga, Samuel; Fernández-Rodríguez, Manuel A.; Marín-Luna, Marta; López, Carlos Silva; Sanz, Roberto [Organic and Biomolecular Chemistry, 2019, vol. 17, # 46, p. 9924 - 9932]

83
[ 59046-72-9 ]
[ 63909-58-0 ]
(E)-1-(4-fluorostyryl)-2-(phenylethynyl)benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	Stage #1: diethyl (4-fluorobenzyl)phosphonate With sodium hexamethyldisilazane In tetrahydrofuran; hexane at -78 - 20℃; for 0.5h; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran; hexane at 20℃;

Reference： [1]Virumbrales, Cintia; Solas, Marta; Suárez-Pantiga, Samuel; Fernández-Rodríguez, Manuel A.; Marín-Luna, Marta; López, Carlos Silva; Sanz, Roberto [Organic and Biomolecular Chemistry, 2019, vol. 17, # 46, p. 9924 - 9932]

84
mesitylstyrenyliodonium triflate [ No CAS ]
[ 63909-58-0 ]
(E)-ethyl styryl 4-fluorobenzylphosphonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%	With 2,6-di-tert-butyl-pyridine; copper(I) thiophene-2-carboxylate In dichloromethane at 50℃; Inert atmosphere; Sealed tube;	3. General procedure for the copper-catalyzed oxygen-alkenylation of dialkyl phosphonates General procedure: CuTC (0.02 mmol, 0.10 equiv), the corresponding alkenyl(aryl)iodonium salt 2 (0.6 mmol, 2 equiv) and a stirring bar were charged in a sealed tube. A solution of phosphonate 1 (0.2 mmol, 1 equiv) in dry dichloromethane (2 ml) and 2,6-di-tert-butylpyridine (0.22 mmol, 1 equiv) was added and the resulting mixture was stirred at 50 °C under an argon atmosphere for 16 h. After this time, the reaction was quenched by addition of saturated aqueous solution of NH4Cl (10 ml) and extracted with CH2Cl (2 × 10 ml). The organic layer was dried over Na2SO4, filtered and solvent was removed under vacuum. The final product was purified by column chromatography on silica gel using n-hexane/AcOEt (1:1) as eluent. 4

Reference： [1]Andón-Rodríguez, Mariña; Fañanás-Mastral, Martín; Gómez-Roibás, Patricia; Vázquez-Galiñanes, Nuria [Beilstein Journal of Organic Chemistry, 2020, vol. 16, p. 611 - 615]

85
[ 63909-58-0 ]
(Z)-2,3-Diethyl-5-phenylpent-2-en-4-ynal [ No CAS ]
1-((1E,3Z)-3,4-diethyl-6-phenylhexa-1,3-dien-5-yn-1-yl)-4-fluorobenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	Stage #1: diethyl (4-fluorobenzyl)phosphonate With sodium hexamethyldisilazane In tetrahydrofuran; hexane at -78 - 20℃; for 0.5h; Stage #2: (Z)-2,3-Diethyl-5-phenylpent-2-en-4-ynal In tetrahydrofuran; hexane at -50 - 20℃;

Reference： [1]Virumbrales, Cintia; Suárez-Pantiga, Samuel; Marín-Luna, Marta; Silva López, Carlos; Sanz, Roberto [Chemistry - A European Journal, 2020, vol. 26, # 38, p. 8443 - 8451]

86
[ 63909-58-0 ]
(E)-2-(3-(4-fluorostyryl)-5-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 2 h / 90 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: JOHN WAYNE CANCER INSTITUTE - WO2020/219718, 2020, A1

87
[ 63909-58-0 ]
(E)-trifluoro(3-(4-fluorostyryl)-5-methoxyphenyl)borane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 2 h / 90 °C / Inert atmosphere 3: methanol / 0.25 h

Reference： [1]Current Patent Assignee: JOHN WAYNE CANCER INSTITUTE - WO2020/219718, 2020, A1

88
[ 63909-58-0 ]
C₁₅H₁₄BFO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 2 h / 90 °C / Inert atmosphere 3: methanol / 0.25 h 4: methanol / 2 h / 25 °C

Reference： [1]Current Patent Assignee: JOHN WAYNE CANCER INSTITUTE - WO2020/219718, 2020, A1

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	63909-58-0	MDL No. :	MFCD06795966
Formula :	C₁₁H₁₆FO₃P	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	FIYRZOAUPPNGAO-UHFFFAOYSA-N
M.W :	246.22	Pubchem ID :	11064685
Synonyms :

Num. heavy atoms :	16
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.45
Num. rotatable bonds :	6
Num. H-bond acceptors :	4.0
Num. H-bond donors :	0.0
Molar Refractivity :	61.43
TPSA :	45.34 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.28 cm/s

Log Po/w (iLOGP) :	2.84
Log Po/w (XLOGP3) :	2.15
Log Po/w (WLOGP) :	3.86
Log Po/w (MLOGP) :	2.51
Log Po/w (SILICOS-IT) :	2.4
Consensus Log Po/w :	2.75

[ CAS No. 63909-58-0 ] {[proInfo.proName]}

Quality Control of [ 63909-58-0 ]

Related Doc. of [ 63909-58-0 ]

Product Details of [ 63909-58-0 ]

Calculated chemistry of [ 63909-58-0 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 63909-58-0 ]

Application In Synthesis of [ 63909-58-0 ]

[ 63909-58-0 ] Synthesis Path-Downstream 1~88

Precautionary Statements-General

Prevention

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Disposal

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Inquiry

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.55

Log S (ESOL) :	-2.6
Solubility :	0.615 mg/ml ; 0.0025 mol/l
Class :	Soluble
Log S (Ali) :	-2.73
Solubility :	0.454 mg/ml ; 0.00184 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.17
Solubility :	0.0166 mg/ml ; 0.0000676 mol/l
Class :	Moderately soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	3.26

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P301+P312-P302+P352-P304+P340-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

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