Name: 67-36-7|4-Phenoxybenzaldehyde|97%
Brand: Ambeed
SKU: A396423
Price: 9.0 USD
Availability: InStock
Rating: 96 (28 reviews)

1
[ 75-52-5 ]
[ 67-36-7 ]
[ 62248-88-8 ]

Yield	Reaction Conditions	Operation in experiment
74%	With sodium hydroxide In methanol at -5℃; for 1h;
74%	With ammonium acetate In acetic acid at 120℃; for 2h;
70%	With cyclohexylamine at 120℃; Microwave irradiation;	2.2. General Procedure 1: Preparation of (E)-(2-nitrovinyl)benzene (1-34, 71-74), (E)-(2-nitroprop-1-en-1-yl)benzenes (35-59, 75-78) and (E)-(2-nitrobut-1-en-1-yl)benzenes (60-70, 79-82) General procedure: To a solution of the appropriate benzaldehyde (3.6 mmol) in glacial acetic acid (4 mL) was added the nitroalkane (7.2mmol) followed by cyclohexylamine (3.6 mmol, 0.4 mL). The reaction mixture was heated under microwave irradiation at 120 °C for 30 min. After cooling, water (10 mL) was added to the reaction and it was allowed to stand. The precipitated nitroethene was isolated by filtration. The filtrate was further diluted with water (20 mL) and extracted with dichloromethane (3 x 10 mL). The organic phases were combined and washed with saturated aqueous NaHCO3 (3 x10 mL). The solution was dried over anhydrous Na2SO4, filtered and all solvent removed in vacuo, to give an oil which was purified by flash column chromatography over silica gel (eluent: dichloromethane/hexane) and recrystallised from ethanol.

67%	With ethylenediammonium bistrifluoroacetate In dimethyl sulfoxide at 110℃; for 9h;	General procedure 1 for the synthesis of starting nitroalkenes 1b-i,k,m-p,t,u. General procedure: Nitroalkenes 1b-i,k,m-p,t,u were prepared similar to literature procedure as follows: Solution of aldehyde (1 equiv.), nitromethane (3 equiv.) and ethylenediammonium bistrifluoroacetate (0.05 equiv.) in DMSO (0.25 mL / 1 mmol of aldehyde) were maintained at 110 °C (oil bath) for 7-22 hours. Reaction mixture was poured into water (ca. 10 mL / 1 mmol of starting aldehyde). Formed precipitate (unless otherwise mentioned) was filtered and recrystallized from EtOH to give target nitroalkenes 1.
	With potassium hydroxide at 0℃;

Reference： [1]Fang, Ge; Hong, Jianquan; Huang, Shuai; Jiang, Chao; Liu, Yang; Zhang, Wei; Zheng, Changge [Organic Letters, 2020]
[2]Chen, Hekai; Kong, Jun; Li, Tian; Xu, Qun; Yin, Hang; Zhang, Liwei [2021, vol. 12, # 10, p. 1771 - 1779]
[3]Byrne, Andrew J.; Bright, Sandra A.; Fayne, Darren; McKeown, James P.; McCabe, Thomas; Twamley, Brendan; Williams, Clive; Meegan, Mary J. [Medicinal Chemistry, 2018, vol. 14, # 2, p. 181 - 199]
[4]Fadeeva, Anastasia A.; Ioffe, Sema L.; Tabolin, Andrey A. [Synthesis, 2020, vol. 52, # 18, p. 2679 - 2688]
[5]Slotta; Soremba [Chemische Berichte, 1936, vol. 69, p. 566,570]

2
[ 67-36-7 ]
[ 2215-78-3 ]
[ 2215-77-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide at 60℃;

Reference： [1]Lock; Kempter [Monatshefte fur Chemie, 1936, vol. 67, p. 24,35]

3
[ 67-36-7 ]
(E)-4-phenoxybenzaldehyde oxime [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With N-hydroxyphthalimide In water at 90℃; for 3h; Sealed tube;	4.2. General procedure for the synthesis of aldoximes General procedure: p-Fluorobenzaldehyde 1a (1.0 mmol), NHPI 2 (1.1 mmol, 1.1 equiv.), and H2O (3 mL) were mixed in a Sealed tube and then stirred at 90 °C for 3 h. After the reaction was completed (monitored by TLC), the reaction mixture was cooled to room temperature and extracted with ethyl acetate (EtOAc). The combined organic layers were dried over Na2SO4, then were concentrated under reduced pressure. The crude residue was purified by flash chromatography on silica gel using hexane/EtOAc as eluent to give the product 3a as a white solid, m.p. 87-88 °C.
67%	With pyridine; hydroxylamine hydrochloride for 1h; Reflux; Inert atmosphere;

Reference： [1]Jiang, Xiaoying; Xu, Xiaohe; Lin, Yuyan; Yan, Yiyan; Li, Pingping; Bai, Renren; Xie, Yuanyuan [Tetrahedron, 2018, vol. 74, # 40, p. 5879 - 5885]
[2]Conlon, Ivie L.; Drennen, Brandon; Lanning, Maryanna E.; Hughes, Samuel; Rothhaas, Rebecca; Wilder, Paul T.; MacKerell, Alexander D.; Fletcher, Steven [ChemMedChem, 2020, vol. 15, # 18, p. 1691 - 1698]
[3]Lock; Kempter [Monatshefte fur Chemie, 1936, vol. 67, p. 24,35]

4
[ 4039-92-3 ]
[ 67-36-7 ]

Reference： [1]Farmaco, Edizione Scientifica,1963,vol. 18,p. 582 - 594
[2]Farmaco, Edizione Scientifica,1964,vol. 19,p. 964 - 971

5
[ 67-36-7 ]
[ 7424-00-2 ]
[ 123760-73-6 ]

Reference： [1]European Journal of Medicinal Chemistry,1988,vol. 23,p. 523 - 532

6
[ 67-36-7 ]
[ 87223-77-6 ]
[ 143603-78-5 ]

Yield	Reaction Conditions	Operation in experiment
72%	With hydrogenchloride In ethanol for 8h; Heating;

Reference： [1]Monge; Aldana; Font; Arraras; Santiago; Lopez-Unzu; Martinez de Irujo; Alberdi [Archiv der Pharmazie, 1992, vol. 325, # 7, p. 439 - 452]

7
[ 1706-12-3 ]
[ 67-36-7 ]

Reference： [1]Journal of Organic Chemistry,1983,vol. 48,p. 1487 - 1491
[2]Monatshefte fur Chemie,1936,vol. 67,p. 24,35
[3]Pharmaceutical Bulletin,1957,vol. 5,p. 397,399

8
[ 459-57-4 ]
[ 108-95-2 ]
[ 67-36-7 ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate In N,N-dimethyl-formamide at 100℃;
93%	With potassium carbonate In N,N-dimethyl-formamide at 120℃;
91%	With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 18h;	4.1 Step 1: Synthesis of 4-phenoxybenzaldehyde P-fluorobenzaldehyde (2.48g, 20.00mmol), phenol (1.88g, 20.00mmol),Potassium carbonate (11.00g, 80.00mmol) and N, N-dimethylformamide (30mL) were added to a 250mL single-necked flask, and the reaction was carried out in an oil bath at 60 ° C for 18 hours. Ice water (200mL) was added to the reaction solution.After stirring for 10 minutes, a solid precipitated out and filtered.The filter cake was washed with water (50 mL x 3) to obtain the title compound (yellow solid, 3.6 g, yield: 91%).

91.2%	With potassium carbonate In N,N-dimethyl-formamide at 110 - 120℃; for 6h; Large scale;	1 Synthesis of 4-phenoxybenzaldehyde (3) 500.0 g of compound 1 and 417.1 g of compound 2 were added to the reaction flask, 4 L of DMF was added, stirring was started, 1113.6 g of potassium carbonate was added, the temperature was raised to 110 ° C to 120 ° C, and the reaction was completed for 6 h. , water was added to quench the reaction, and IPAC was added for extraction. The organic phase was washed with water and concentrated to remove most of the IPAC. Under reduced pressure distillation, collect 4050 of cuts to be DMF, collect 120125 of cuts, obtain 727.6 g compound 3, yield is 91.2%
85%	With cesium fluoride/clinoptilolite In dimethyl sulfoxide at 110℃; for 2.5h;
81%	With potassium fluoride on basic alumina; 18-crown-6 ether In dimethyl sulfoxide at 140℃; for 16h;
76%	With potassium carbonate In N,N-dimethyl-formamide at 110℃; for 16h; Microwave irradiation;	12.1 Step-1: Synthesis of 4-phenoxybenzaldehyde To a stirred solution of 4-fluorobenzaldehyde (2 g, 8.19 mmol, 21.0 eq.) and phenol (2.63 g, 21.0 mmol, 1.0 eq.) in DMF (20 mL) was added K2CO3 (8.6 g, 63.0 mmol, 3 eq.) The resulting mixture heated at 110° C. for 16 h. Following this, reaction was allowed to cool to RT and filtered through celite pad, the celite pad washed with ethyl acetate and water. The aqueous layer was separated extracted using ethyl acetate (3*30 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na2SO4, filtered and concentrated under vacuum to get the solid residue. The crude was purified by normal phase silica-gel column provided title compound as white solid (3.2 g, 76%). LCMS: 199.1 [M+1]+; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 9.93 (s, 1H) 7.85 (d, J=8.77 Hz, 2H) 7.42 (t, J=8.11 Hz, 2H) 7.20-7.28 (m, 2H) 7.03-7.13 (m, 4H).
71%	With potassium carbonate In N,N-dimethyl acetamide Heating;
59%	With potassium carbonate In N,N-dimethyl-formamide at 90℃; for 6h;	4-Phenoxybenzaldehyde (22) To a solution of phenol (1.1 g, 12.09 mmol) inN,N-dimethylformamide (12 mL) were added potassium carbonate (2.2 g, 16.11 mmol)and4-fluorobenzaldehyde(1.0 g, 8.06 mmol)at room temperature. The reaction mixture was stirred at 90oCfor 6 hours. After the reaction was completed, the crude mixture was cooled to room temperature, added towater and extracted with ethyl acetate. The organic layer was dried over anhydrousNa2SO4andconcentrated under reduced pressure. The residue was purified by flash column chromatograph (0-10% ethyl acetate/hexane) to give the product as a colorless oil (945 mg, 59%);1H NMR (400 MHz,CDCl3)δ9.92 (s, 1H), 7.85 (d,J= 8.8 Hz, 2H), 7.44-7.40 (m, 2H), 7.25-7.20 (m, 1H), 7.09 (d,J= 8.4 Hz, 2H), 7.06 (d,J= 8.8 Hz, 2H);13C NMR (100 MHz, CDCl3)δ190.9, 163.4, 155.3, 132.1, 131.4, 130.3, 125.1, 120.6, 117.7; LC/MS (ESI+)m/z199.1 [M + H]+.
59%	With potassium carbonate In N,N-dimethyl-formamide at 90℃; for 6h;	4-Phenoxybenzaldehyde (22) To a solution of phenol (1.1 g, 12.09 mmol) inN,N-dimethylformamide (12 mL) were added potassium carbonate (2.2 g, 16.11 mmol)and4-fluorobenzaldehyde(1.0 g, 8.06 mmol)at room temperature. The reaction mixture was stirred at 90oCfor 6 hours. After the reaction was completed, the crude mixture was cooled to room temperature, added towater and extracted with ethyl acetate. The organic layer was dried over anhydrousNa2SO4andconcentrated under reduced pressure. The residue was purified by flash column chromatograph (0-10% ethyl acetate/hexane) to give the product as a colorless oil (945 mg, 59%);1H NMR (400 MHz,CDCl3)δ9.92 (s, 1H), 7.85 (d,J= 8.8 Hz, 2H), 7.44-7.40 (m, 2H), 7.25-7.20 (m, 1H), 7.09 (d,J= 8.4 Hz, 2H), 7.06 (d,J= 8.8 Hz, 2H);13C NMR (100 MHz, CDCl3)δ190.9, 163.4, 155.3, 132.1, 131.4, 130.3, 125.1, 120.6, 117.7; LC/MS (ESI+)m/z199.1 [M + H]+.
	With potassium carbonate In N,N-dimethyl acetamide at 155℃;
	With potassium carbonate In N,N-dimethyl acetamide Heating;
	With potassium carbonate In N,N-dimethyl acetamide at 150℃;
	With potassium carbonate In lithium hydroxide monohydrate; N,N-dimethyl-formamide	R.33 4-Phenoxybenzaldehyde REFERENCE EXAMPLE 33 4-Phenoxybenzaldehyde A suspension of 4-fluorobenzaldehyde (30.5 g, 246 mmol),phenol (23.5 g, 249 mmol), and potassium carbonate (34.8 g, 252 mmol) in N,N-dimethylformamide (500 mL) was heated under reflux for 11.5 hours. The reaction solution was cooled to room temperature, and then the solvent was distilled off under reduced pressure. The resultant residue was combined with water, and the organic material was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate, and then the solvent was distilled off under reduced pressure to obtain the mixture (48.1 g) containing the title compound. This was used in the next reaction without further purification. An oil.
	With Cs₂CO₃ In N,N-dimethyl-formamide for 1h; Reflux;	63 A mixture of 12.4 g of 4-fluorobenzaldehyde, 12.0 g of phenol, 18.0 g of potassium carbonate and 60 ml of DMF was heated to reflux for 1 hour. After, water was added to the reaction mixture, it was then extracted with ethyl acetate. The organic layer was successively washed with diluted hydrochloric acid, water and a saturated saline solution, and it was then dried over magnesium sulfate, followed by concentration under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 21.0 g of 4-phenoxybenzaldehyde.
	With potassium carbonate In N,N-dimethyl-formamide Inert atmosphere; Reflux;	7.1.1.Synthesis of 4-substituted benzaldehyde (3a-i) General procedure: A mixture of substituted phenol 1a-i (37.4mmol), 4-fluorobenzaldehyde 2 (37.4 mmol) and potassium carbonate (38.8 mmol) in N,N-dimethylformamide (30 ml) was refluxed for 16-18 h under nitrogen. After cooling, the product was extracted from the reaction mixture and purified by chromatography.
	With potassium carbonate In N,N-dimethyl-formamide
	With potassium carbonate In N,N-dimethyl-formamide Reflux; Inert atmosphere;
	With potassium carbonate In N,N-dimethyl-formamide Inert atmosphere; Reflux;	7.1.2. Synthesis of 4-substituted benzaldehyde (5a-i) General procedure: A mixture of substituted phenol 3a-i (37.4 mmol), 4-fluoro benzaldehyde 4 (37.4 mmol) and potassium carbonate (38.8 mmol) in N,N-dimethylformamide (30 ml) was refluxed for 16-18 h under nitrogen. After cooling, the product was extracted from the reaction mixture and purified by chromatography.
	With potassium carbonate In N,N-dimethyl-formamide at 100℃;
	With potassium carbonate In N,N-dimethyl-formamide Inert atmosphere; Reflux;
	With potassium carbonate In N,N-dimethyl-formamide Inert atmosphere; Reflux;
	With potassium carbonate In N,N-dimethyl-formamide Reflux;
	With copper (I) cyanide; potassium carbonate In N,N-dimethyl-formamide at 110℃; for 7h;	3.A Example 3 Add dimethylformamide (DMF) 150kg, p-fluorobenzaldehyde 50kg, phenol 37.8kg, potassium carbonate 112kg, cuprous cyanide 0.5kg to the reaction vessel, stir and heat, and incubate at 110°C for 7 hours.After cooling to room temperature, the inorganic salt was removed by filtration. The filtrate was further depressurized and the solvent dimethylformamide was recovered. The residue was cooled to room temperature and 250 kg of methanol was added for dissolution. The residue was4-benzyloxybenzaldehyde
	With copper (I) cyanide; potassium carbonate at 110℃; for 7h; Large scale;	3.A; 1 Example 3 A. 150kg of dimethyl sulfate (DMS), 50kg of fluorobenzaldehyde, 37.8kg of phenol, 112kg of potassium carbonate, and 0.5kg of cuprous cyanide are added to the reaction vessel, stirring and heating, and the reaction is held at 110°C for 7 hours.After cooling to room temperature, the inorganic salt was removed by filtration, and the filtrate was further depressurized to recover the solvent, dimethyl sulfate. The residue was cooled to room temperature, 250 kg of methanol was added for dissolution, and the residue was 4-phenoxybenzaldehyde.
	With Cs₂CO₃ In N,N-dimethyl-formamide at 90℃; for 3h;	36 Example 36: 4-phenoxybenzaldehyde (24)[00198] To a stirring solution of p-fluorobenzaldehyde (1.6 mmol, 0.2 g) in dimethylformamide (8 mL) was added phenol (3.52 mmol, 0.33 g) and cesium carbonate (3.52 mmol, 1.15 g). The reaction mixture was headed to 90 0C for 3 hours at which time the reaction mixture was cooled to room temperature and filtered through a medium fritted funnel. The reaction mixture was then diluted with 125 mL of ethyl acetate and extracted with eight 15 mL portions of water followed by one 10 mL portion of brine. The organic layer was then dried with magnesium sulfate and evaporated to dryness. The title product was purified by column chromatography and 0.237 g (1.2 mmol) was recovered. 1H NMR (300 MHz, CDCl3) δ 9.91 (s, IH), 8.02 (s, OH), 7.92 - 7.79 (m, 2H), 7.49 - 7.37 (m, 2H), 7.23 (t, J = 8.0, 2H), 7.14 - 7.01 (m, 4H), 6.89 (t, J = 8.3, 2H). 13C NMR (75 MHz, CDCl3) δ 191.28, 163.56, 156.41, 155.26, 132.28, 131.38, 130.41, 129.79, 125.23, 120.69, 120.45, 117.79, 115.61.
	With tripotassium phosphate tribasic; tetrabutylammonium bromide; nickel (II) chloride at 100℃; for 4h;	General procedure for the etherificationof nitrobenzenes with phenols/alcohols General procedure: A vessel was charged with nitrobenzene (0.5 mmol), phenol/alcohol (1 mmol), NiCl2(0.1 mmol), and K3PO4(2 mmol). To this mixture, was added TBAB (1.5 g) and heated to100 °C. Progress of the reaction was monitored by TLC.After completion of the reaction, silica gel (1 g) was addedto the reaction vessel and the mixture was added to a columnchromatography. Petroleum ether/ethylacetate (10:1)was used as the eluent to separate the desired product.
	With potassium carbonate In dimethyl sulfoxide at 110℃; Inert atmosphere;	18 Example 18 (E) -2- (2-methyl-3- (4-phenoxyphenyl) acrylamido) benzoic acid (Compound 18) Phenol (705 mg, 7.5 mmol), p-fluorobenzaldehyde (625 mg, 5.0 mmol) andK2CO3 (1.38g, 10.0mmol) was dispersed in 5mL DMSO,Protected with argon and reacted at 110 ° C overnight.Cool to room temperature, add an appropriate amount of water, extract with ethyl acetate, combine the organic phases,It was washed three times with saturated brine, dried over anhydrous sodium sulfate, concentrated by spin drying, and purified by column to obtain 4-phenoxybenzaldehyde.
	With Cs₂CO₃ In N,N-dimethyl-formamide at 80℃;
	With potassium carbonate In N,N-dimethyl-formamide at 120℃; for 12h;
	With potassium carbonate In N,N-dimethyl-formamide for 18h; Reflux; Inert atmosphere;	2.2.1. Synthetic Procedure for 4-substituted benzaldehyde (3a-i) General procedure: Phenols 1a-i (37.5mmol), p-fluorobenzaldehyde 2 (37.5mmol) and potassium carbonate (38.9mmol) were mixed in N,N-DMF (30ml) and reflux under nitrogen for 18 h. On cooling, the product was separated from the reaction mixture and was purified by using chromatographic techniques

Reference： [1]Chen, Qiong; Chen, Tao; Gao, Meng-Qi; Wang, Yu-Xia; Yang, Guang-Fu; Zhang, Rui; Zhu, Xiao-Lei [Letters in drug design and discovery, 2022, vol. 19, # 4, p. 263 - 268]
[2]Dubost, Emmanuelle; Babin, Victor; Benoist, Florian; Hébert, Alexandra; Barbey, Pierre; Chollet, Céline; Bouillon, Jean-Philippe; Manrique, Alain; Pieters, Grégory; Fabis, Frédéric; Cailly, Thomas [Organic Letters, 2018, vol. 20, # 19, p. 6302 - 6305]
[3]Current Patent Assignee: GUANGDONG HEC TECHNOLOGY HOLDING CO., LTD. - CN110317200, 2019, A Location in patent: Paragraph 0209-0212
[4]Current Patent Assignee: SUZHOU PENGXU PHARMATECH CO LTD - CN114436878, 2022, A Location in patent: Paragraph 0020-0022
[5]Keipour, Hoda; Hosseini, Abolfazl; Afsari, Amir; Oladee, Razieh; Khalilzadeh, Mohammad A.; Ollevier, Thierry [Canadian Journal of Chemistry, 2015, vol. 94, # 1, p. 95 - 104]
[6]Sawyer, J. Scott; Schmittling, Elisabeth A.; Palkowitz, Jayne A.; Smith III, William J. [Journal of Organic Chemistry, 1998, vol. 63, # 18, p. 6338 - 6343]
[7]Current Patent Assignee: INTEGRAL BIOSCIENCES PRIVATE LTD - US2020/206233, 2020, A1 Location in patent: Paragraph 0268-0269
[8]Yeager; Schissel [Synthesis, 1991, # 1, p. 63 - 68]
[9]Abed, Dhulfiqar Ali; Hu, Longqin; Lee, Sumi; Nguyen, Mai-Uyen; Verzi, Michael P. [European Journal of Medicinal Chemistry, 2022, vol. 237]
[10]Abed, Dhulfiqar Ali; Hu, Longqin; Lee, Sumi; Nguyen, Mai-Uyen; Verzi, Michael P. [European Journal of Medicinal Chemistry, 2022, vol. 237]
[11]Dimmock, Jonathan R.; Puthucode, Ramanan N.; Smith, Jennifer M.; Hetherington, Mark; Quail, J. Wilson; Pugazhenthi, Uma; Lechler, Terry; Stables, James P. [Journal of Medicinal Chemistry, 1996, vol. 39, # 20, p. 3984 - 3997]
[12]Desai, Ranjit C.; Han, Wei; Metzger, Edward J.; Bergman, Jeffrey P.; Gratale, Dominick F.; MacNaul, Karen L.; Berger, Joel P.; Doebber, Thomas W.; Leung, Kwan; Moller, David E.; Heck, James V.; Sahoo, Soumya P. [Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 16, p. 2795 - 2798]
[13]Pfefferkorn, Jeffrey A.; Greene, Meredith L.; Nugent, Richard A.; Gross, Rebecca J.; Mitchell, Mark A.; Finzel, Barry C.; Harris, Melissa S.; Wells, Peter A.; Shelly, John A.; Anstadt, Robert A.; Kilkuskie, Robert E.; Kopta, Laurice A.; Schwende, Francis J. [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 10, p. 2481 - 2486]
[14]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP1270577, 2003, A1
[15]Current Patent Assignee: Sumitomo Chemical (w/o Dongwoo Fine-Chem); SUMITOMO CHEMICAL COMPANY LIMITED - EP2248423, 2010, A1 Location in patent: Page/Page column 261
[16]Location in patent: experimental part Tripathi, Laxmi; Singh, Ranjit; Stables, James P. [European Journal of Medicinal Chemistry, 2011, vol. 46, # 2, p. 509 - 518]
[17]Location in patent: scheme or table Kumar, Praveen; Shrivastava, Birendra; Pandeya, Surendra N.; Stables, James P. [European Journal of Medicinal Chemistry, 2011, vol. 46, # 4, p. 1006 - 1018]
[18]Location in patent: experimental part Tripathi, Laxmi; Singh, Ranjit [Asian Journal of Chemistry, 2011, vol. 23, # 1, p. 447 - 450]
[19]Location in patent: experimental part Tripathi, Laxmi; Kumar, Praveen; Singh, Ranjit; Stables, James P. [European Journal of Medicinal Chemistry, 2012, vol. 47, # 1, p. 153 - 166]
[20]Location in patent: scheme or table Nakamura, Tsuyoshi; Asano, Masayoshi; Sekiguchi, Yukiko; Mizuno, Yumiko; Tamaki, Kazuhiko; Kimura, Takako; Nara, Futoshi; Kawase, Yumi; Shimozato, Takaichi; Doi, Hiromi; Kagari, Takashi; Tomisato, Wataru; Inoue, Ryotaku; Nagasaki, Miyuki; Yuita, Hiroshi; Oguchi-Oshima, Keiko; Kaneko, Reina; Watanabe, Nobuaki; Abe, Yasuyuki; Nishi, Takahide [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 4, p. 1788 - 1792]
[21]Location in patent: experimental part Kumar, Praveen; Tripathi, Laxmi [Medicinal Chemistry, 2012, vol. 8, # 3, p. 337 - 348]
[22]Kumar, Praveen; Shrivastava, Birendra; Pandeya, Surendra N.; Tripathi, Laxmi; Stables, James P. [Medicinal Chemistry Research, 2012, vol. 21, # 9, p. 2428 - 2442]
[23]Tripathi, Laxmi; Kumar, Praveen [European Journal of Medicinal Chemistry, 2013, vol. 64, p. 477 - 487]
[24]Current Patent Assignee: JIANGSU WANLONG TECH - CN107793299, 2018, A Location in patent: Paragraph 0017-0019
[25]Current Patent Assignee: JIANGSU WANLONG TECH - CN107778147, 2018, A Location in patent: Paragraph 0015; 0017; 0019
[26]Current Patent Assignee: UNIVERSITY OF VIRGINIA - WO2009/146112, 2009, A1 Location in patent: Page/Page column 42-43
[27]Zamiran, Fatemeh; Ghaderi, Arash [Journal of the Iranian Chemical Society, 2019, vol. 16, # 2, p. 293 - 299]
[28]Current Patent Assignee: EAST CHINA UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN110357789, 2019, A Location in patent: Paragraph 0255-0257
[29]Bamba, Fante; Jin, Jinshan; Tai, Phang C.; Wang, Binghe [Heterocyclic Communications, 2020, vol. 26, # 1, p. 76 - 83]
[30]Wu, Xin; Yu, Yongbo; Huang, Tonghui [Journal of Enzyme Inhibition and Medicinal Chemistry, 2021, vol. 36, # 1, p. 1236 - 1247]
[31]Kumar, Praveen; Tripathi, Laxmi [Medicinal Chemistry, 2021, vol. 17, # 10, p. 1175 - 1193]

9
[ 67-36-7 ]
[ 33208-99-0 ]
(S)-2-(4-Phenoxy-benzylamino)-propionamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1998,vol. 41,p. 579 - 590

10
[ 7647-01-0 ]
[ 7446-70-0 ]
[ 74-90-8 ]
[ 2974-94-9 ]
[ 71-43-2 ]
[ 101-84-8 ]
[ 67-36-7 ]

Reference： [1]Chemische Berichte,1935,vol. 68,p. 2059,2063

11
[ 67-36-7 ]
[ 2215-78-3 ]

Yield	Reaction Conditions	Operation in experiment
92%	With 5%-palladium/activated carbon; hydrogen In methanol at 70℃; Autoclave;	3.B; 2 Example 3 B. The 4-phenoxybenzaldehyde solution in methanol was transferred to an autoclave, palladium carbon 2kg with palladium content of 5% was added, and the temperature was controlled at 70°C to introduce hydrogen gas.Keep the hydrogen pressure at 5kg/cm2 until the hydrogen pressure in the autoclave no longer decreases, cool to room temperature, remove the palladium carbon under anaerobic conditions, and recover the methanol from the filtrate.The recovered organic material was cooled and crystallized to obtain 4-phenoxybenzyl alcohol with a content of 99.5% and an overall yield of 92.0%.
84%	With sodium tetrahydridoborate In ethanol at 20℃; for 2h;
57%	With sodium tetrahydridoborate In methanol at 0 - 20℃; for 1.16667h;	(4-Phenoxyphenyl)methanol(23) To a solution of22(945 mg, 4.77 mmol) in methanol (20 mL) was added sodium borohydride (180 mg, 4.77 mmol) at 0°C. After stirring at 0°Cfor 10 minutes, the reaction mixture was warmed to room temperature and stirred for 1 hour. After the reaction was completed, the crude mixture was added to water and extracted with dichloromethane. The organic layer was dried over anhydrousNa2SO4andconcentrated under reduced pressure to give the product as a white solid. (539 mg, 57%);1H NMR (400 MHz,DMSO-d6)δ7.39-7.32 (m, 4H), 7.11 (t,J= 7.6 Hz, 1H), 6.99-6.96 (m, 4H), 5.19 (t,J= 5.6 Hz, 1H, OH), 4.48 (d,J= 5.6 Hz, 2H);13C NMR (100 MHz, DMSO-d6)δ157.0, 155.2, 137.8, 130.0, 128.2, 123.2, 118.5, 118.2, 62.4.

57%	With sodium tetrahydridoborate In methanol at 0 - 20℃; for 1.16667h;	(4-Phenoxyphenyl)methanol(23) To a solution of22(945 mg, 4.77 mmol) in methanol (20 mL) was added sodium borohydride (180 mg, 4.77 mmol) at 0°C. After stirring at 0°Cfor 10 minutes, the reaction mixture was warmed to room temperature and stirred for 1 hour. After the reaction was completed, the crude mixture was added to water and extracted with dichloromethane. The organic layer was dried over anhydrousNa2SO4andconcentrated under reduced pressure to give the product as a white solid. (539 mg, 57%);1H NMR (400 MHz,DMSO-d6)δ7.39-7.32 (m, 4H), 7.11 (t,J= 7.6 Hz, 1H), 6.99-6.96 (m, 4H), 5.19 (t,J= 5.6 Hz, 1H, OH), 4.48 (d,J= 5.6 Hz, 2H);13C NMR (100 MHz, DMSO-d6)δ157.0, 155.2, 137.8, 130.0, 128.2, 123.2, 118.5, 118.2, 62.4.
	With sodium borohydride In ethanol	P.58 Production of 4-phenoxybenzyl alcohol PRODUCTION EXAMPLE 58 Production of 4-phenoxybenzyl alcohol Sodium borohydride (0.48 g) was added to a solution of 4.96 g of 4-phenoxybenzaldehyde in 20 ml of ethanol, and the mixture was stirred at room temperature for 1.5 hours. After the completion of the concentration, the residue was extracted with tert-butylmethyl ether and with water. The organic layer was concentrated to give 4.84 g of 4-phenoxybenzyl alcohol. Properties of the compound: 1 H-NMR(CDCl3, δ): 4.67(2H, d, J=5.7 Hz), 6.99-7.01(4H, m), 7.10(1H, t, J=7.4 Hz), 7.32-7.35(4H, m).
	With sodium tetrahydridoborate In ethanol at 20℃; for 1.5h;	58 Production Example 58 Production of 4-phenoxybenzyl alcohol Sodium borohydride (0.48 g) was added to a solution of 4.96 g of 4-phenoxybenzaldehyde in 20 ml of ethanol, and the mixture was stirred at room temperature for 1.5 hours.. After the completion of the concentration, the residue was extracted with tert-butylmethyl ether and with water.. The organic layer was concentrated to give 4.84 g of 4-phenoxybenzyl alcohol. Properties of the compound: 1H-NMR(CDCl3, δ): 4..67(2H, d, J=5.7Hz), 6.99-7.01(4H, m), 7.10(1H, t, J=7.4 Hz), 7.32-7.35(4H, m)
94 %Spectr.	With 1-hydrosilatrane; sodium hydroxide In N,N-dimethyl-formamide at 20℃; for 0.5h;
	With 5%-palladium/activated carbon; hydrogen In methanol at 70℃; Autoclave;	3.B Example 3 Transfer the 4-benzyloxybenzaldehyde in methanol to the autoclave. add 2 kg palladium carbon with 5% palladium temperature control at 70 °C into hydrogen,Keep the hydrogen pressure at 5kg/cm2, The hydrogen pressure in the autoclave is no longer reduced, it is cooled to room temperature, and palladium carbon is filtered off under anaerobic conditions. The filtrate recovers methanol, The recovered organic material was cooled and crystallized to obtain 4-benzyloxybenzyl alcohol with a content of 98.2% and an overall yield of 87.0%.
	With sodium tetrahydridoborate In tetrahydrofuran; methanol

Reference： [1]Current Patent Assignee: JIANGSU WANLONG TECH - CN107778147, 2018, A Location in patent: Paragraph 0015; 0016; 0018
[2]Szajnman, Sergio H.; Yan, Wen; Bailey, Brian N.; Docampo, Roberto; Elhalem, Eleonora; Rodriguez, Juan B. [Journal of Medicinal Chemistry, 2000, vol. 43, # 9, p. 1826 - 1840]
[3]Abed, Dhulfiqar Ali; Hu, Longqin; Lee, Sumi; Nguyen, Mai-Uyen; Verzi, Michael P. [European Journal of Medicinal Chemistry, 2022, vol. 237]
[4]Abed, Dhulfiqar Ali; Hu, Longqin; Lee, Sumi; Nguyen, Mai-Uyen; Verzi, Michael P. [European Journal of Medicinal Chemistry, 2022, vol. 237]
[5]Current Patent Assignee: ASTELLAS PHARMA INC. - US6166219, 2000, A
[6]Current Patent Assignee: ASTELLAS PHARMA INC. - US6352985, 2002, B1 Location in patent: Page column 152
[7]Skrypai, Vladislav; Hurley, Joseph J. M.; Adler, Marc J. [European Journal of Organic Chemistry, 2016, vol. 2016, # 12, p. 2207 - 2211]
[8]Current Patent Assignee: JIANGSU WANLONG TECH - CN107793299, 2018, A Location in patent: Paragraph 0017-0020
[9]Chen, Qiong; Chen, Tao; Gao, Meng-Qi; Wang, Yu-Xia; Yang, Guang-Fu; Zhang, Rui; Zhu, Xiao-Lei [Letters in drug design and discovery, 2022, vol. 19, # 4, p. 263 - 268]

12
[ 2215-78-3 ]
[ 67-36-7 ]

Yield	Reaction Conditions	Operation in experiment
98%	With hydrogenchloride; tert.-butylnitrite; TEMPOL; oxygen; chloranil In neat (no solvent) at 20℃; for 6h; Green chemistry;
94%	With γ-picolinium chlorochromate; silica gel In dichloromethane at 20℃; for 11h;
94%	With potassium carbonate In n-heptane at 80℃; for 24h;	S4. Procedure for the synthesis of aldehydes and ketones General procedure: A magnetic stir bar, 0.5 mmol alcohol and 3 mL n-heptane solvent were added to 20 mL glass tube. Then, 35mg catalyst and 10 mol% of K2CO3 were added. The glass tube containing reaction mixture was f itted withseptum and connected to a balloon containing one bar of air. Then the glass tube was placed into a preheatedaluminum block at 85°C. Temperature inside the reaction tube was measured to be 80 oC and this temperaturehas been taken as the reaction temperature. The reaction was allowed to progress under continuous stirringfor the required time at 80 °C. Af ter completion of the reaction, the glass tube was cooled down to roomtemperature. Afterwards, the catalyst was f iltered-off and washed with ethyl acetate. The solvent f rom thef iltrate containing the reaction products was removed in vacuum and the corresponding aldehyde/ketone waspurif ied by column chromatography. All products were analyzed by GC-MS and NMR spectroscopy analysis.In the case of yields determined the by GC, 100 μL n-hexadecane was added to the reaction vial containingthe products and diluted with ethyl acetate. Then, the reaction mixture containing catalyst and products wasf iltered through a plug of silica and the filtrate containing product was analyzed by GC.

92%	With ammonium dichromate(VI); calcium chloride at 60℃; for 0.83h;
82%	With DDB In acetonitrile for 7.2h; Heating;
82%	With tetrabutylammomium bromide; oxygen; acetic acid; sodium nitrite at 70℃; for 16h; Green chemistry;

Reference： [1]Dong, Yanli; Zhao, Xiaomei; Liu, Renhua [Chinese Journal of Chemistry, 2015, vol. 33, # 9, p. 1019 - 1023]
[2]Salehi; Khodaei; Yazdanipoor [Polish Journal of Chemistry, 2003, vol. 77, # 10, p. 1281 - 1286]
[3]Bartling, Stephan; Beller, Matthias; Chandrashekhar, Vishwas G.; Jagadeesh, Rajenahally V.; Rabeah, Jabor; Rockstroh, Nils; Senthamarai, Thirusangumurugan [Chem, 2022, vol. 8, # 2, p. 508 - 531]
[4]Shirini; Zolfigol; Safari [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2005, vol. 44, # 11, p. 2383 - 2386]
[5]Shirini; Tajik; Jalili [Synthetic Communications, 2001, vol. 31, # 19, p. 2885 - 2889]
[6]Sheykhan, Mehdi; Moafi, Hadi Fallah; Abbasnia, Masoumeh [RSC Advances, 2016, vol. 6, # 56, p. 51347 - 51355]

13
[ 67-36-7 ]
[ 64910-46-9 ]
[ 357156-62-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2001,vol. 11,p. 1545 - 1548

14
[ 67-36-7 ]
[ 68827-43-0 ]
2-(4-phenoxy-phenyl)-3H-benzoimidazole-5-carboxamidine [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2001,vol. 11,p. 1545 - 1548

15
[ 67-36-7 ]
[ 76-05-1 ]
[ 162167-97-7 ]
[1-(4-phenoxybenzyl)piperidin-3-yl]methanamine bis(trifluoroacetate) salt [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2004,p. 2723 - 2737

16
[ 67-36-7 ]
[ 2360-20-5 ]
2-(4-Phenoxy-phenyl]-1H-benzoimidazole-5-sulfonic Acid Amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With sodium metabisulfite In N,N-dimethyl-formamide at 100℃; for 18h;

Reference： [1]Arienti, Kristen L.; Brunmark, Anders; Axe, Frank U.; McClure, Kelly; Lee, Alice; Blevitt, Jon; Neff, Danielle K.; Huang, Liming; Crawford, Shelby; Pandit, Chennagiri R.; Karlsson, Lars; Breitenbucher, J. Guy [Journal of Medicinal Chemistry, 2005, vol. 48, # 6, p. 1873 - 1885]

17
[ 67-36-7 ]
[ 711007-44-2 ]
2-(4-phenoxy-phenyl)-1H-benzoimidazole-4-carboxylic acid amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 1873 - 1885

18
[ 67-36-7 ]
[ 39033-67-5 ]
1-methyl-2-(4-phenoxy-phenyl)-1H-benzoimidazole-5-carboxylic acid amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With sodium metabisulfite In N,N-dimethyl-formamide at 100℃;
65%	With sodium metabisulfite In N,N-dimethyl-formamide at 100℃;	III.B; 7.d In the first step of Scheme 7, the fluoro group of 4-fluoro-3-nitrobenzoic acid 2 was displaced with methylamine followed by conversion of the acid to a primary amide, and nitro reduction giving the diamine intermediate 3. The diamine was then oxidatively condensed under standard conditions with 4-aryloxybenzaldehyde giving compound 4 in good yield. Compound 7 was prepared in a similar fashion starting from 3-fluoro-4-nitrobenzoic acid.

Reference： [1]McClure, Kelly J.; Huang, Liming; Arienti, Kristen L.; Axe, Frank U.; Brunmark, Anders; Blevitt, Jon; Guy Breitenbucher [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 7, p. 1924 - 1928]
[2]Current Patent Assignee: UNIVERSITY OF MASSACHUSETTS - US2008/125358, 2008, A1 Location in patent: Page/Page column 15-16

19
[ 67-36-7 ]
[ 16642-79-8 ]
3-[4-(4-phenoxy-benzylamino)-phenyl]-propionic acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 1584 - 1589

20
[ 867-13-0 ]
[ 67-36-7 ]
[ 945414-28-8 ]

Yield	Reaction Conditions	Operation in experiment
67%	Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.583333h; Stage #2: 4-phenoxy benzaldehyde In tetrahydrofuran; hexane at -78 - 20℃; Further stages.;
67%	Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.583333h; Stage #2: 4-phenoxy benzaldehyde In tetrahydrofuran; hexane at 25℃;	6 Example 6: l-Oxo-l-[5-(2-pyridyl)oxazol-2-yl]-3-(4-phenoxyphenyl)propane(Hf). Ethyl (£)-3-(4-phenoxyphenyl)acrylate (S28). A solution of triethylphosphonoacetate (1.40 g, 6.25 mmol, 1.25 equiv) in 20 niL of anhydrous THF at -78 °C was treated with rc-BuLi (2.4 M in hexanes, 3.26 mL, 7.82 mmol, 1.5 equiv). After stirring for 35 min, 4-phenoxybenzaldehyde (990 mg, 5.0 mmol, 1 equiv) in anhydrous THF (15 mL) was added dropwise. The reaction mixture was allowed to warm at 25 °C and was stirred overnight. The reaction was quenched with saturated aqueous NH4Cl and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered and concentrated. Column chromatography (SiO2, 4 x 8 cm, 10% EtOAc-hexanes) afforded S28 (540 mg, 2.03 mmol, 67%) as a colorless oil: 1H NMR (CDCl3, 500 MHz) 7.66 (d, IH, J= 16.2 Hz), 7.50 (d, 2H, J= 8.8 Hz), 7.38 (dd, 2H, J= 8.8, 7.6 Hz), 7.17 (t, IH5 J= 7.4 Hz), 7.07-7.05 (m, 2H), 6.98 (d, 2H, J= 8.8 Hz), 6.35 (d, IH, J= 16.2 Hz), 4.26 (q, 2H, J= 7.0 Hz), 1.35 (t, 3H, J = 7.1 Hz).

Reference： [1]Hardouin, Christophe; Kelso, Michael J.; Romero, F. Anthony; Rayl, Thomas J.; Leung, Donmienne; Hwang, Inkyu; Cravatt, Benjamin F.; Boger, Dale L. [Journal of Medicinal Chemistry, 2007, vol. 50, # 14, p. 3359 - 3368]
[2]Current Patent Assignee: SCRIPPS RESEARCH - WO2008/147553, 2008, A1 Location in patent: Page/Page column 30

21
[ 67-36-7 ]
[ 4039-92-3 ]

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 1826 - 1840

22
1,2,3,4-tetrahydro-8-methyl-[1]benzothieno[3,2-c]pyridine hydrochloride [ No CAS ]
[ 67-36-7 ]
1,2,3,4-tetrahydro-8-methyl-2-[(4-phenoxyphenyl)-methyl][1]benzothieno[3,2-c]pyridine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With hydrogen In methanol at 50℃;	B1.c Example B1 A mixture of 8-methyl-1,2,3,4-tetrahydrobenzothieno[3,2-c]pyridine hydrochloride (1:1) (0.01 mol), 4-phenoxybenzaldehyde (0.01 mol) and potassium acetate (1 g) in methanol (150 ml) hydrogenated at 50° C. After uptake of H2 (1 equiv), the catalyst was filtered off and the filtrate was evaporated. The residue was washed with water and this mixture was extracted with CH2Cl2. The separated organic layer was dried, filtered and the solvent evaporated. The residue was converted into the hydrochloric acid salt (1:1), filtered off and dried, yielding 2.9 g of 1,2,3,4-tetrahydro-8-methyl-2-[(4-phenoxyphenyl)methyl]-[1]-benzothieno[3,2,-c)pyridine hydrochloride (69%) (comp. 10).

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - US6352999, 2002, B1 Location in patent: Page column 17

23
1,2,3,4-tetrahydro-7-methoxy-[1]benzothieno[3,2-c]pyridine hydrochloride [ No CAS ]
[ 67-36-7 ]
1,2,3,4-tetrahydro-7-methoxy-2-[(4-phenoxyphenyl)-methyl][1]benzothieno[3,2-c]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	With hydrogen; potassium acetate In methanol at 50℃;	B1.b Example B1 A mixture of intermediate (6) (0.0059 mol) and 4-phenoxybenzaldehyde (0.0076 mol) with potassium acetate (1 g) in methanol (150 ml) was hydrogenated at 50° C. with platinum on activated charcoal (1 g) as a catalyst in the presence of thiophene (1 ml of a 5% solution). After uptake of H2 (1 equiv), the catalyst was filtered off and the solvent was evaporated. The residue was washed with water and extracted with CH2Cl2. The separated organic layer was dried, filtered and the solvent evaporated. The residue was crystallized from 2-propanol, filtered off and dried, yielding 1.2 g (50%) of 1,2,3,4-tetrahydro-7-methoxy-2-[(4-phenoxyphenyl)methyl)][1]-benzothieno[3,2-c]pyridine (comp. 2).

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - US6352999, 2002, B1 Location in patent: Page column 16-17

24
6-Ethoxycarbonyl-2H-2-diethylphosphoryl-1,4-benzothiazin-3(4H)-one [ No CAS ]
[ 67-36-7 ]
6-ethoxycarbonyl-2H-2-(4-phenoxybenzylidene)-1,4-benzothiazin-3(4H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With sodium ethanolate In tetrahydrofuran; ethanol; water at 20℃;	801.3 Step 3: t-Butyl 6-Ethoxycarbonyl-2H-2-(4-phenoxybenzyl)-1,4-benzothiazin-3(4H)-one-4-ylacetate To a stirred solution of p-phenoxybenzaldehyde (796 mg) and 6-ethoxycarbonyl 2H-2-diethylphosphoryl-1,4-benzothiazine-3(4H)-one (1.00 g) in 80% ethanol aq. (10 mL) and THF (10 mL), a solution of sodium ethoxide (400 mg) in ethanol (5 mL) was added dropwise. The reaction mixture was stirred at r.t. overnight. The solvent was removed under reduced pressure. To the residue, ethyl acetate (5 ml) and water (10 ml) was added and the solid product was collected by filtration. After drying under reduced pressure, the product (980 mg, 88%) was given as a yellow solid.

Reference： [1]Current Patent Assignee: SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem); Sumitomo Pharma (in: Sumitomo Chemical) - US6713477, 2004, B1 Location in patent: Page column 92

25
[ 16647-80-6 ]
[ 67-36-7 ]
(2S,3R,4R,5S)-2-(hydroxymethyl)-1-[(4-phenoxyphenyl)methyl]-3,4,5-piperidinetriol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With (polystyrylmethyl)trimethylammonium cyanoborohydride; acetic acid In methanol at 20℃; for 16h;	19 [EXAMPLE 19; 3,4, 5-PIPERIDINETRIOL, 2- (HYDROXYMETHYL)-L- [ (4-PHENOXYPHENYL) METHYL] -,] (2S, 3R, 4R, 5S) To a mixture of 3, 4, [5-PIPERIDINETRIOL,] [2-(HYDROXYMETHYL)-,] (2S, 3R, 4R, [5S)] (57mg, 0.35mmol), 4- phenoxybenzaldehyde [(200MG,] l. Olmmol) and (polystyrylmethyl) trimethylammonium cyanoborohydride (200mg, 0. [87MMOL)] in methanol [(2ML)] was added acetic acid (0. [2ML).] The resultant mixture was stirred at room temperature for 16 h. The crude reaction mixture was purified using a plug of acidic Dowex [50X4-] 200 resin [(1G),] which had been pre-washed with methanol [(LOML).] The resin was eluted with methanol [(25ML)] to remove all non-basic side products. The desired compound was then eluted using a solution of 7: 1 methanol/ammonium hydroxide [(25ML).] The resulting solution was concentrated to a small volume [(LRNL)] and freeze dried to afford the title compound as a white solid (86mg, 71%).'H NMR (d4-methanol) 8 2.60 [(1H,] dd, J = 12.5, 9.5 Hz), 2.73 [(1H,] dd, J [= 12.] 5,5 Hz), 3.09 [(1H,] m), 3.41 [(1H,] m), 3.54 [(1H,] m), 3.74-3. 95 (5H, m), 6.91-6. 99 (4H, [M),] 7.06-7. 13 [(1H,] m), 7.30-7. 37 (4H, m). MS [M/Z] 346.3 [(M+H) +.]

Reference： [1]Current Patent Assignee: IDORSIA PHARMACEUTICALS LTD - WO2004/7453, 2004, A1 Location in patent: Page 24

26
[ 6304-16-1 ]
[ 67-36-7 ]
[ 216504-30-2 ]

Yield	Reaction Conditions	Operation in experiment
66%		EXAMPLE A-11 4-[3-methyl-5-(4-phenoxyphenyl)-1H-pyrazol-4-yl]pyridine 4-Pyridylacetone (1.5 g, 12 mmol), 4-phenoxybenzoldehyde 92.1 g, 10.6 mmol), acetic acid (110 mg, 1.8 mmol), and piperidine (110 mg, 1.3 mmol) were dissolved in toluene (30 mL) and heated for 2 hours at reflux in a flask equipped with a Dean-Stark trap. The solution was cooled to room temperature and ethyl acetate was added to precipitate a solid, which was collected on a filter plate. A sample (223 mg) of this solid was heated with p-toluensulfonyl hydrazide (348 mg, 1.81 mmol) in ethylene glycol with potassium hydroxide (77 mg) at 110 C. for 0.5 hour. The work up procedure was the same as that in Example A-10. 4-[3-Methyl-5-(4-phenoxyphenyl)-1H-pyrazol-4-yl]pyridine was obtained (100 mg, 66% yield): Anal. Calc'd for C21H17N3O+0.1H2O: C, 76.62; H, 5.27; N, 12.76. Found: C, 76.37; H, 5.19; N, 12.64. MS (M+H): 328 (base peak).

Reference： [1]Patent: US6979686,2005,B1 .Location in patent: Page/Page column 129

27
[ 67-36-7 ]
[ 19525-87-2 ]
N-(4-phenoxybenzyl)-O-benzyl-D,L-serine methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With sodium borohydrid; triethylamine; In methanol; ethyl acetate;	(2) 9.50 g (38.7 mmol) of O-benzyl-D,L-serine methyl ester hydrochloride was dissolved in 160 ml of methanol, treated with 8.09 ml (58.1 mmol) of triethylamine and 6.78 ml (38.7 mmol) of 4-phenoxybenzaldehyde, and then stirred at room temperature for 20 hours. 1.46 g (38.7 mmol) of sodium borohydride was added and the mixture was stirred at room temperature for 2.5 hours. The reaction mixture was concentrated, treated with ethyl acetate, washed with water and saturated brine, and then dried over anhydrous sodium sulfate. After concentrating followed by column chromatography on silica gel eluding with hexane:ethyl acetate (80:20-60:40) followed by concentrating into dryness, 13.0 g (yield: 86%) of N-(4-phenoxybenzyl)-O-benzyl-D,L-serine methyl ester as a colorless oil. 1H-NMR (300 MHz, CDCl3); delta: 7.30 (9H, m), 7.08 (1H, m), 6.98 (4H, m), 4.54 (1H, d, J=12.4 Hz), 4.50 (1H, d, J=12.4 Hz), 3.86 (1H, d, J=12.8 Hz), 3.73 (3H, s), 3.70 (3H, m), 3.51 (1H, t, J=4.9 Hz).

Reference： [1]Patent: US6420415,2002,B1

28
[ 67-36-7 ]
[ 113411-62-4 ]
[ 110-17-8 ]
[ 263543-72-2 ]

Yield	Reaction Conditions	Operation in experiment
	thiophene; palladium-carbon; In methanol; isopropyl alcohol;	EXAMPLE B8 Starting material <strong>[113411-62-4]1,2,3,4-tetrahydrobenzofuro[2,3-c]pyridine hydrochloride</strong> (1:1) (0.01 mol) was alkalized, extracted and the solvent evaporated, to give the free base (1.4 g, 0.008 mol). A mixture of said free base and 4-phenoxybenzaldehyde (0.01 mol) in methanol (150 ml) was hydrogenated with Pd/C 10% (1 g) as a catalyst in the presence of thiophene 4% (1 ml). After uptake of H2 (1 equiv), the catalyst was filtered off and the filtrate was evaporated. The residue was purified by column chromato-graphy over silica gel (eluent: CH2/Cl2/(CH3OH/NH3) 98/2). The desired fraction were collected and the solvent was evaporated. The residue was dissolved in 2-propanol and converted into the (E)-2-butenedioic acid salt (1:1) with (E)-2-butenedioic acid (1.2 g). The mixture was boiled, then allowed to cool to RT while stirring. The precipitate was filtered off and dried, yielding 1.80 g (49%) of 1,2,3,4-tetrahydro-2-[(4-phenoxy-phenyl)methyl]benzofuro[2,3-c]pyridine (E)-2-butenedioate (1:1) (compound 33)

Reference： [1]Patent: US6495555,2002,B1

29
[ 67-36-7 ]
[ 56553-60-7 ]
[ 169943-40-2 ]

Yield	Reaction Conditions	Operation in experiment
	With acetic acid; methylamine; In ethanol;	Preparation 4 N-Methyl-N-(4-phenoxybenzyl)amine STR21 To a solution of 4-phenoxybenzaldehyde (4.4 ml, 25 mmol) in ethanol (50 ml) was added methylamine (3.0 ml of 33% solution in ethanol, 25 mmol) and acetic acid (1.4 ml, 25 mmol), and the mixture was stirred under an atmosphere of nitrogen. After 20 minutes sodium tri(acetoxy)borohydride (10.5 g, 50 mmol) was added and stirring was continued for 16 hours. The mixture was diluted with 2 M aqueous hydrochloric acid (200 ml) and washed with diethyl ether (2100 ml). The aqueous layer was basified to pH 12 with concentrated aqueous ammonia solution and extracted with dichloromethane (4100 ml). The combined organic layers were dried (Na2 SO4), the solvent was evaporated under reduced pressure and the residue was purified by flash chromatography on silica gel (dichloromethane/methanol/aqueous ammonia solution 95:5:0 to 94:5:1) to give the titled compound as a colourless oil (3.3 g). 1 H NMR (300 MHz, CDCl3): 2.33 (s, 1 H), 2.47 (s, 3 H), 3.73 (s, 2 H), 6.93-7.02 (m, 4 H), 7.02-7.13 (m, 1 H), 7.23-7.37 (m, 4 H).

Reference： [1]Patent: US6090852,2000,A

30
[ 67-36-7 ]
[ 122594-72-3 ]

Yield	Reaction Conditions	Operation in experiment
93%	In ethanol; ethyl acetate	1.B N-i-Butyl-N-(4-phenoxybenzyl)amine EXAMPLE 1B N-i-Butyl-N-(4-phenoxybenzyl)amine 4-Phenoxybenzaldehyde (10.0 g, 0.05 mmol), excess isobutylamine and 1.0 g of 10% Pd/O in 200 mL of ethanol were stirred under an inert atmosphere for 16 hours followed by an atmosphere of hydrogen for 16 hours. After removal of the catalyst by filtration through Celite, the filtrate was concentrated under reduced pressure to give the crude product as an oil. The oil was dissolved in ether and precipitated by treatment with anhydrous HCl. The solid was filtered, washed with ether, and partitioned between ethyl acetate and 1M NaOH. The ethyl acetate solution was washed with brine, dried over Na2 SO4, and evaporated to give the title compound in 93% yield.
93%	In ethanol; ethyl acetate	1.B N-i-Butyl-N-(4-phenoxybenzyl)amine EXAMPLE 1B N-i-Butyl-N-(4-phenoxybenzyl)amine 4-Phenoxybenzaldehyde (10.0 g, 0.05 mol), excess isobutylamine and 1.0 g of 10% Pd/C in 200 mL of ethanol were stirred under an inert atmosphere for 16 hours followed by an atmosphere of hydrogen for 16 hours. After removal of the catalyst by filtration through a filter and (CELITE), the filtrate was concentrated under reduced pressure to give the crude product as an oil. The oil was dissolved in ether and precipitated by treatment with anhydrous HCl. The solid was filtered, washed with ether, and partitioned between ethyl acetate and 1M NaOH. The ethyl acetate solution was washed with brine, dried over Na2 SO4, and evaporated to give the title compound in 93% yield.

Reference： [1]Current Patent Assignee: ABBOTT LABORATORIES INC - US5631401, 1997, A
[2]Current Patent Assignee: ABBOTT LABORATORIES INC - US5783593, 1998, A

31
[ 67-36-7 ]
ammonium chloride [ No CAS ]
[ 2215-78-3 ]

Yield	Reaction Conditions	Operation in experiment
92%	With borane In tetrahydrofuran	36.A 4-Phenoxybenzyl alcohol EXAMPLE 36A 4-Phenoxybenzyl alcohol A 0° C. solution of 4-phenoxybenzaldehyde (5.0 g, 25.2 mmol) in 10 mL THF under an atmosphere of dry N2 was treated with borane (1.0M in THF, 11.25 mL) for 1 hour. A saturated NH4 Cl solution was added, and the mixture was diluted with ethyl acetate. The organic layer was washed with 1M HCl, 5% NaHCO3 and brine, dried and concentrated in vacuo to give the title compound in 92% yield.
4.7 g (92%)	With borane In tetrahydrofuran	65.A 4-Phenoxybenzyl alcohol EXAMPLE 65A 4-Phenoxybenzyl alcohol A solution of 4-phenoxybenzaldehyde (5.0 g, 25 mmol) in dry tetrahydrofuran (10 mL) at 0° C. was treated with borane (1M in tetrahydrofuran, 11.25 mL). After 45 minutes, the reaction was quenched with saturated NH4 Cl, diluted with ethyl acetate, and washed with 1M HCl, 5% NaHCO3, and brine, and dried over Na2 SO4, and concentrated under reduced pressure to give 4.7 g (92%) of 4-phenoxybenzyl alcohol.

Reference： [1]Current Patent Assignee: ABBOTT LABORATORIES INC - US5631401, 1997, A
[2]Current Patent Assignee: ABBOTT LABORATORIES INC - US5783593, 1998, A

32
[ 67-36-7 ]
[ 7732-18-5 ]
[ 2215-78-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide In tetrahydrofuran	81.A 4-Phenoxybenzyl alcohol EXAMPLE 81A 4-Phenoxybenzyl alcohol A solution of 4-phenoxybenzaldehyde (10.0 g, 50 mmol) and 10 mL dry THF was added dropwise to a 0° C. suspension of lithium aluminum hydride (2.1 g, 55.3 mmol) and 100 mL dry THF. The reaction mixture was stirred for 1 hour at 0° C., then was quenched successively with 2.1 mL H20, 2.1 mL 10% NaOH, and 6.3 mL H2 O. The resultant slurry was stirred for 1.5 hours at room temperature, then was filtered through Celite and the filtrate was evaporated under reduced pressure to afford the title compound (9.9 g) as a white solid. 1 H-NMR (300 MHz, CDCl3) δ 1.68 (t, 1H), 4.68 (d, 2H), 7.00 (m, 4H), 7.10 (t, 1H), 7.35 (m, 4H). MS (DCl/NH3) m/e 183 (M+1, -H2 O)+.
	With sodium hydroxide In tetrahydrofuran	64.A 4-Phenoxybenzyl alcohol EXAMPLE 64A 4-Phenoxybenzyl alcohol A solution of 4-phenoxybenzaldehyde (10.0 g, 50 mmol) and 10 mL dry THF was added dropwise to a 0° C. suspension of lithium aluminum hydride (2.1 g, 55.3 mmol) and 100 mL dry THF. The reaction mixture was stirred for 1 hour at 0° C., then was quenched successively with 2.1 mL H2 O, 2.1 mL 10% NaOH, and 6.3 mL H2 O. The resultant slurry was stirred for 1.5 hours at room temperature, then was filtered through Celite and the filtrate was evaporated under reduced pressure to afford the title compound (9.9 g) as a white solid. 1 H NMR (300 MHz, CDCl3) δ1.68 (t, 1H), 4.68 (d, 2H), 7.00 (m, 4H), 7.10 (t, 1H), 7.35 (m, 4H). MS (DCl/NH3) m/e 183 (M+1, --H2 O)+.

Reference： [1]Current Patent Assignee: ABBOTT LABORATORIES INC - US5631401, 1997, A
[2]Current Patent Assignee: ABBOTT LABORATORIES INC - US5783593, 1998, A

33
methyltriphenylphosphium bromide [ No CAS ]
[ 67-36-7 ]
[ 4973-29-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium tert-butylate; In tetrahydrofuran; hexane;	EXAMPLE 67A 4-Phenoxystyrene To a suspension of methyltriphenylphosphium bromide (7.85 g, 22 mmol) in THF (10 mL) was added potassium tert-butoxide (1.0M solution in THF, 22 mL). After 30 minutes, 4-phenoxybenzaldehyde (3.96 g, 20 mmol) was added to the above mixture. The reaction was diluted with equal volume of hexane after 20 minutes and filtered through silica gel. The residue was rinsed and washed with 20% ether in hexane. Concentration of the filtrate gave the crude product as an off white solid which was used without further purification.

Reference： [1]Patent: US5631401,1997,A

34
[ 67-36-7 ]
[ 6053-81-2 ]
N-(cyclopentylmethyl)-N-(4-phenoxybenzyl)amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
3.4 g (80%)	With sodium cyanoborohydride In methanol; dichloromethane	101.A N-Cyclopentylmethyl-N-(4-phenoxybenzyl)amine EXAMPLE 101A N-Cyclopentylmethyl-N-(4-phenoxybenzyl)amine 4-Phenoxybenzaldehyde (3.0 g, 15.1 mmol) and cyclopentylmethylamine (1.49 g, 15.1 mmol) were dissolved in methanol (85 mL) under nitrogen at room temperature. Sodium cyanoborohydride (0.95 g, 15.1 mmol) was added, and stirring was continued for 48 hours. The solvent was evaporated, and the residue was suspended in ether, washed with brine, and dried over Na2 SO4. The ether was evaporated, and the crude product was chromatographed on silica gel eluding with 3% methanol in methylene chloride to provide 3.4 g (80%) of the title compound as a colorless oil. 1 H NMR (CDCl3, 300 MHz) δ 1.10-1.24 (m, 2H), 1.45-1.67 (m, 2H), 1.71-1.90 (m, 3H), 2.06 (p, J=7.5 Hz, 1H), 2.58 (d, J=7.5 Hz, 2H), 3.79 (s, 2H), 6.95-7.05 (m, 4H) 7.09 (tt, J=7.5, 1.5 Hz, 1H), 7.28-7.38 (m, 4H). MS (DCl/NH3) m/e 282 (M+H)+.

Reference： [1]Current Patent Assignee: ABBOTT LABORATORIES INC - US5631401, 1997, A

35
[ 67-36-7 ]
[ 1779-49-3 ]
[ 4973-29-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium tert-butylate; In tetrahydrofuran; hexane;	EXAMPLE 38A 4-Phenoxystyrene To a suspension of methyltriphenylphosphonium bromide (7.85 g, 22 mmol) in THF (10 mL) was added potassium tert-butoxide (1.0M solution in THF, 22 mL). After 30 minutes, 4-phenoxybenzaldehyde (3.96 g, 20 mmol) was added to the above mixture. The reaction was diluted with equal volume of hexane after 20 minutes and filtered through silica gel (80 g). The residue was rinsed and washed with 20% ether in hexane. Concentration of the filtrate in vacuo gave the crude product as an off white solid which was used without further purification.
		Method 6[0033] General conditions for the preparation of alkenes: under a nitrogen atmosphere, 0.25 M methyltriphenylphosphonium bromide (1.1 equiv) dissolved in tetrahydrofuran was cooled to 0 0C after which the mixture was treated drop wise with sodium hexamethyldisilazane (NaHMDS) in tetrahydrofuran (1.0 M, 1.2 equiv). After stirring an additional 30 min at 0 0C, a given aldehyde or ketone is added and the reaction is allowed to warm slowly to 23 0C overnight. The mixture was quenched saturated ammonium chloride and concentrated to remove the tetrahydrofuran. The mixture was then diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The concentrated reaction mixture was purified by flash silica gel chromatography (ethyl acetate / hexanes) to provide the desired alkene.
9.4 g		To a suspension of methyl triphenylphosphonium bromide (CAS Number 1779-49- 3, 19.84 g, 55.5 mmol) in TOP (50 mL) was added potassium tert-butoxide (CAS Number 865-47-4, 10.2 g, 90.9 mmol) at ambient temperature and the reaction mixture was stirred for 30 minutes. 4- phenoxybenzaldehyde (CAS Number 67-36-7, 10.0 g, 50.5 mmol) was added to the reaction mixture at ambient temperature and stirred for 15 h. The resulting reaction mixture was diluted with n -hexane (100 mL) and stirred for 40 min. Hie obtained suspension was filtered through silica gel (60-120 mesh size) and the filtrate was evaporated under reduced pressure yielding l-phenoxy-4-vinylbenzene (9.4 g, 47.94 mmol). *H NMR (400 MHz, (4X1 0 5 ppm: 7.34-7.42 (m, 11 1). 7.11 -7.15 (m . 1H), 6.97-7.054 (m, 11 1}. 6.68-6.75 (m, 1H), 5.69 (dd, J=0.8, 17.6 Hz, 1H), 5.22 (dd, J=0.8, 11.2 Hz, 1H).

Reference： [1]Chemical Communications,2018,vol. 54,p. 4473 - 4476
[2]Organic Letters,2016,vol. 18,p. 6428 - 6431
[3]Patent: US5783593,1998,A
[4]Patent: WO2010/135360,2010,A1 .Location in patent: Page/Page column 174; 208
[5]Patent: WO2019/133813,2019,A1 .Location in patent: Paragraph 0142

36
[ 67-36-7 ]
[ 3096-81-9 ]

Yield	Reaction Conditions	Operation in experiment
80%		REFERENCE EXAMPLE 34 4-Phenoxybenzonitrile The title compound was obtained from 4-phenoxybenzaldehyde by the method similar to that in Reference Example 32. Yield: 80%. 1H NMR (CDCl3) δ 6.97-7.19 (4H, m), 7.20-7.28 (1H, m), 7.37-7.46 (2H, m), 7.57-7.64 (2H, m).

Reference： [1]Patent: EP1270577,2003,A1
[2]Journal of the American Chemical Society,2016,vol. 138,p. 2885 - 2888

37
[ 67-36-7 ]
[ 74572-15-9 ]
[ 1020673-55-5 ]

Yield	Reaction Conditions	Operation in experiment
8%		Example 34: (S)-4-(4-Phenoxy-benzyl)-2-phenyl-morpholine; 200mg of (S)-2-Phenyl-morpholine (see synthesis in Example 1) was dissolved in 2mL of dichloroethane and 253 muL of 4-Phenoxy-benzaldehyde was added. The reaction was stirred at room temperature 30 minutes and then 467mg of sodium triacetoxyboro hydride was added. The reaction was stirred overnight at room temperature. The reaction solution was then washed with aqueous saturated sodium bicarbonate solution several times followed by a brine wash. The organics were dried over sodium sulfate, filtered and concentrated in vacuo. Purification by preparatory chromatography gave the title compound. 8percent yield. EI m/z 346= MH+

Reference： [1]Patent: WO2008/48914,2008,A1 .Location in patent: Page/Page column 22

38
[ 1122-91-4 ]
[ 108-95-2 ]
[ 67-36-7 ]

Yield	Reaction Conditions	Operation in experiment
94%	With potassium carbonate In dimethyl sulfoxide at 20℃;
94%	With sodium hydroxide In water monomer at 80℃; for 3h;
93%	With potassium hydroxide In water monomer at 20℃; for 12h; Green chemistry;

92%	With tripotassium phosphate tribasic; copper (I) iodide; (1E,2E)-1,2-bis(2-phenylhydrazono)ethane In acetonitrile at 60℃; for 12h; Inert atmosphere;
91%	With tripotassium phosphate tribasic; 2-((di-adamantan-1-yl)phosphaneyl)-1-(2,6-diisopropylphenyl)-1H-imidazole; palladium diacetate In toluene at 100℃; for 10h; Inert atmosphere;
87%	With potassium carbonate In dimethyl sulfoxide at 110℃; for 12h;
84%	With tetrabutylammonium bromide; Cs₂CO₃ In N,N-dimethyl-formamide at 145℃; for 24h; Inert atmosphere;	2.3 General procedure for CuO-Fe₃O₄-catalyzed O-arylation of phenols with aryl halides General procedure: To a stirred solution of phenol (2.2mmol) in DMF (15.0mL) under an argon atmosphere were added CuO-Fe3O4 (0.2mmol), TBAB (0.2mmol), Cs2CO3 (326mg, 1.0mmol) and aryl halide (2.0mmol). The reaction mixture was stirred at the required temperature (145°C) for 24 h. At the end of reaction, the catalyst was removed by a magnet and the resulting mixture was quenched with water and extracted with EtOAc. The organic phases were dried over MgSO4, followed by evaporation under reduced pressure to remove the solvent. The residue was purified by column chromatography on silica gel to afford the desired product.
84%	With Cs₂CO₃ In ethanol at 80℃; for 20h; Inert atmosphere;
84%	With 6C₁₂H₆O₄^(2-)4Gd⁽³⁺⁾8H₂O; Cs₂CO₃ In N,N-dimethyl-formamide at 80℃; for 7h;	2.5. General procedure for the catalytic reactions General procedure: 0.151 g (1 mmol) of p-nitrobromobenzene and 0.103 g (1 mmol)of p-cresol were added with 0.487 g (1.5 mmol) of solid cesium carbonatein 3 mL dehydrated dimethylformamide (DMF) solvent to a15 mL round-bottom flask. 0.005 g of compound 1 was added tothe reaction medium and the resulting mixture was stirred undercontinuous heating at 80 C for seven hours. The conversion ofthe reaction was monitored by the thin layered chromatography(TLC) method. After completion of the reaction mixture, it wascooled to room temperature and purged on ice cold water. Theaqueous layer was extracted three times with ethylacetate(6 mL). The combined organic layer thus collected was washedwith a brine solution, dried over anhydrous sodium sulfate andconcentrated in vacuum. The collected residue was further purifiedby column chromatography on silica-gel (60-120 mesh), elutingwith an n-hexane/ethyl acetate mixture to get the desired product.The product was analyzed by 1H NMR spectroscopy and elementalanalysis, and compared with the literature data.
83%	With copper oxide (I); Cs₂CO₃ In N,N-dimethyl-formamide at 140℃; for 24h; Inert atmosphere; Green chemistry;	General procedure for the synthesis of diarylethers by using Cu2O/Cu-CNTsas a catalyst General procedure: In an oven-dried 50 mL round-bottomed flask with a condenser, phenol (1.0 mmol),bromobenzene (1.2 mmol), Cs2CO3 (1.0 mmol) and Cu2O/Cu-CNTs catalyst (0.06 g) were addedunder nitrogen atmosphere, followed by addition of DMSO (10 mL). The reaction mixture washeated in an oil bath at 140 and stirred at this temperature for 24 h. After the completion of thereaction (monitored by TLC), the reaction mixture was filtered. The filtrate was extracted withethyl acetate (3×10 mL) by adding a small amount of saturated aqueous NaCl solution. Theorganic layer was dried with anhydrous MgSO4 and concentrated to get the crude product. Theresulting residue was purified by column chromatography on silica gel to provide the desiredproduct.
83%	With C₁₉H₁₈ClFeNPdSe; Cs₂CO₃ In dimethyl sulfoxide at 110℃; for 6h;
80%	With Pd₁₆S₇; potassium carbonate In dimethyl sulfoxide at 100℃; for 3h;
79%	With copper(II) oxide; potassium hydroxide In N,N-dimethyl acetamide at 27℃; for 24h; Inert atmosphere; Sealed tube;	Procedure for C-O/C-S cross coupling General procedure: A magnetic stirring bar, nanocrystalline CuO (10 mg, 3 mol %), KOH (112 mg, 2 mmol) and phenol/substituted phenol/ thiophenol (1.2 mmol) were added into an oven-dried flask (25 mL). The flask was sealed with a septum, followed by three cycles of evacuation and filling with dry nitrogen. Then aryl halide (1 mmol) and N,N-dimethyl acetamide (DMAc) (4 mL) were injected through a syringe. The flask was sealed and stirred under nitrogen until the completion of the reaction (as monitored by TLC or GC). The catalyst was recovered from the reaction mixture and washed several times with ethyl acetate. The catalyst-free reaction mixture was quenched with brine solution and the product was extracted with ethyl acetate. The combined organic extracts were dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated and the residue was purified by column chromatography on silica gel (hexane/ethyl acetate, 80/20) to afford the product with high purity.
77%	With [Ni^II(N-((6-fluoropyridin-2-yl)methyl)(pyridin-2-yl)-N-(pyridin-2-ylmethyl)methanamine)(acetate)(H₂O)][BPh₄]; potassium carbonate In dimethyl sulfoxide at 120℃; for 12h;	2.5. Catalytic O-arylation of phenols General procedure: In a round bottom flask, mixture of phenol (1.2 mmol), aryl halides(1 mmol) and K2CO3 (2 mmol) have been taken in 5 mL DMSO. Thecomplexes (1-3) (4 mol%) were then added into the reaction mixture.Thereafter, the reaction mixture was heated at 120 C for the given time.The progress of reaction was monitored through TLC made of silica andafter the maximum conversion reached, reactions were quenched bywater after cooling and extracted using ethyl acetate. Then, it was driedover anhydrous sodium sulphate and subjected to GC analysis usingShimadzu GC-2014. The products were detected and quantified by GC(FID) with the following temperature program: injector temperature240 C; initial temperature 50 C, isothermal for 3 min then heating rate10 C min 1 to 200 C and thereafter another isothermal of 3 min; FIDtemperature 250 C.
	With pyridine In N,N-dimethyl-formamide
	With C₂₅H₂₂Cl₂NPPd; potassium carbonate In dimethyl sulfoxide Reflux;	2.5.2. O -Arylation of phenol (C-O coupling reaction) General procedure: A mixture of aryl halide (1.0 mmol), phenol (1.2 mmol), potas- sium carbonate (2.0 mmol), catalyst (0.1 mol%) and 4.0 mL of dimethylsulfoxide (DMSO) was taken in an oven dried round bot- tom flask of 100 mL capacity and refluxed at 110 °C. The progress of the reaction was monitored through TLC. When the stage of the maximum conversion reached, the mixture was cooled to room temperature. The mixture was extracted using ethyl acetate and washed three times with water. The organic layer was made free from water using anhydrous sodium sulphate. Finally, the solvent was evaporated to obtain the product. The conversion has been es- timated using 1 H NMR study.

Reference： [1]Joshi, Hemant; Sharma, Kamal Nayan; Sharma, Alpesh K.; Prakash, Om; Singh, Ajai Kumar [Chemical Communications, 2013, vol. 49, # 68, p. 7483 - 7485]
[2]Joshi, Hemant; Sharma, Alpesh K.; Singh, Ajai K. [RSC Advances, 2020, vol. 10, # 11, p. 6452 - 6459]
[3]Hajipour, Abdol R.; Check, Maryam; Khorsandi, Zahra [Applied Organometallic Chemistry, 2017, vol. 31, # 11]
[4]Location in patent: experimental part Liu, Yu-Hua; Li, Gang; Yang, Lian-Ming [Tetrahedron Letters, 2009, vol. 50, # 3, p. 343 - 346]
[5]Hu, Tongjie; Schulz, Thomas; Torborg, Christian; Chen, Xiaorong; Wang, Jun; Beller, Matthias; Huang, Jun [Chemical Communications, 2009, # 47, p. 7330 - 7332]
[6]Arora, Aayushi; Kumar, Arun; Kumar, Sushil; Nautiyal, Divyanshu; Oswal, Preeti; Singh, Siddhant [New Journal of Chemistry, 2022, vol. 46, # 8, p. 3578 - 3587]
[7]Zhang, Ying-Peng; Shi, Ai-Hong; Yang, Yun-Shang; Li, Chun-Lei [Chinese Chemical Letters, 2014, vol. 25, # 1, p. 141 - 145]
[8]Maity, Tanmoy; Saha, Debraj; Das, Soma; Bhunia, Susmita; Koner, Subratanath [Catalysis Communications, 2014, vol. 58, p. 141 - 148]
[9]Ghosh, Pameli; Maity, Tanmoy; Biswas, Saptarshi; Debnath, Rakesh; Koner, Subratanath [Polyhedron, 2021, vol. 194]
[10]Zhang, Ying-Peng; Jiao, Ya-Cong; Yang, Yun-Shang; Li, Chun-Lei [Tetrahedron Letters, 2013, vol. 54, # 48, p. 6494 - 6497]
[11]Sharma, Alpesh K.; Joshi, Hemant; Bhaskar, Renu; Kumar, Satyendra; Singh, Ajai K. [Dalton Transactions, 2017, vol. 46, # 8, p. 2485 - 2496]
[12]Singh, Poornima; Singh, Ajai K. [Dalton Transactions, 2017, vol. 46, # 30, p. 10037 - 10049]
[13]Babu, S. Ganesh; Karvembu [Tetrahedron Letters, 2013, vol. 54, # 13, p. 1677 - 1680]
[14]Kerbib, Wissame; Kumar, Arun; Kumar, Sushil; Nautiyal, Divyanshu; Singh, Siddhant [Inorganica Chimica Acta, 2020, vol. 517]
[15]Location in patent: body text Gucma, Miroslaw; Golebiewski, W. Marek [Monatshefte fur Chemie, 2010, vol. 141, # 4, p. 461 - 469]
[16]Arora, Aayushi; Kaushal, Jolly; Kumar, Arun; Nautiyal, Divyanshu; Oswal, Preeti; Singh, Siddhant [Journal of Molecular Structure, 2022, vol. 1253]

39
[ 36881-42-2 ]
[ 67-36-7 ]

Yield	Reaction Conditions	Operation in experiment
92%	With water; 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione at 50℃; for 0.666667h; Ionic liquid; Inert atmosphere;

Reference： [1]Location in patent: experimental part Dake, Satish A.; Kulkarni, Ravibhushan S.; Kadam, Vijay N.; Modani, Sandesh S.; Bhale, Jayant J.; Tathe, Sumangala B.; Pawar, Rajendra P. [Synthetic Communications, 2009, vol. 39, # 21, p. 3898 - 3904]

40
[ 104-88-1 ]
[ 108-95-2 ]
[ 67-36-7 ]

Yield	Reaction Conditions	Operation in experiment
91%	With potassium carbonate In N,N-dimethyl-formamide at 110℃; for 12h;
91%	With potassium carbonate In dimethyl sulfoxide at 20℃;
83%	With tripotassium phosphate tribasic; 2-((di-adamantan-1-yl)phosphaneyl)-1-(2,6-diisopropylphenyl)-1H-imidazole; palladium diacetate In toluene at 100℃; for 10h; Inert atmosphere;

77%	With copper(II) oxide; potassium hydroxide In N,N-dimethyl acetamide at 27℃; for 22h; Inert atmosphere; Sealed tube;	Procedure for C-O/C-S cross coupling General procedure: A magnetic stirring bar, nanocrystalline CuO (10 mg, 3 mol %), KOH (112 mg, 2 mmol) and phenol/substituted phenol/ thiophenol (1.2 mmol) were added into an oven-dried flask (25 mL). The flask was sealed with a septum, followed by three cycles of evacuation and filling with dry nitrogen. Then aryl halide (1 mmol) and N,N-dimethyl acetamide (DMAc) (4 mL) were injected through a syringe. The flask was sealed and stirred under nitrogen until the completion of the reaction (as monitored by TLC or GC). The catalyst was recovered from the reaction mixture and washed several times with ethyl acetate. The catalyst-free reaction mixture was quenched with brine solution and the product was extracted with ethyl acetate. The combined organic extracts were dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated and the residue was purified by column chromatography on silica gel (hexane/ethyl acetate, 80/20) to afford the product with high purity.
77%	With sodium hydroxide In water monomer at 80℃; for 6h;
62%	With potassium carbonate In dimethyl sulfoxide at 110℃; for 12h;
10%	With cerium(IV) dioxide; potassium hydroxide In dimethyl sulfoxide at 110℃; for 5h; Air atmosphere;

Reference： [1]Arundhathi; Damodara; Likhar, Pravin R.; Kantam, M. Lakshmi; Saravanan; Magdaleno, Travis; Kwon, Sun Hee [Advanced Synthesis and Catalysis, 2011, vol. 353, # 9, p. 1591 - 1600]
[2]Joshi, Hemant; Sharma, Kamal Nayan; Sharma, Alpesh K.; Prakash, Om; Singh, Ajai Kumar [Chemical Communications, 2013, vol. 49, # 68, p. 7483 - 7485]
[3]Hu, Tongjie; Schulz, Thomas; Torborg, Christian; Chen, Xiaorong; Wang, Jun; Beller, Matthias; Huang, Jun [Chemical Communications, 2009, # 47, p. 7330 - 7332]
[4]Babu, S. Ganesh; Karvembu [Tetrahedron Letters, 2013, vol. 54, # 13, p. 1677 - 1680]
[5]Joshi, Hemant; Sharma, Alpesh K.; Singh, Ajai K. [RSC Advances, 2020, vol. 10, # 11, p. 6452 - 6459]
[6]Arora, Aayushi; Kumar, Arun; Kumar, Sushil; Nautiyal, Divyanshu; Oswal, Preeti; Singh, Siddhant [New Journal of Chemistry, 2022, vol. 46, # 8, p. 3578 - 3587]
[7]Location in patent: scheme or table Agawane, Sandeep M.; Nagarkar, Jayashree M. [Tetrahedron Letters, 2011, vol. 52, # 41, p. 5220 - 5223]

41
[ 108-86-1 ]
[ 123-08-0 ]
[ 67-36-7 ]

Yield	Reaction Conditions	Operation in experiment
92%	With potassium hydroxide at 60℃; for 0.5h; Green chemistry;	3.4. General procedure for O-arylation General procedure: In a round-bottomed flask equipped with mechanical stirrer,aryl halide (1 mmol), phenol (1.2 mmol), catalyst (3 mg) and KOH(2 mmol) were stirred in solvent-free conditions under air atmosphereat 60 °°C for 0.5 h. The progress of the reaction was monitored by TLC (eluent: n-hexaneeethyl acetate, 5:1) and GC. After completion of the reaction, CH2Cl2 (15 ml) was added and the catalyst was separated using an external magnet. The organic layerwas washed with water (3 x 10 ml) and dried over anhydrous MgSO4. The product was isolated by column chromatography (n-hexane-ethyl acetate, 5:1) to afford the corresponding products.The products were characterized by their physical properties,melting points, and FT-IR, 1H NMR and 13C NMR [66-68].
69%	With sodium dodecyl-sulfate; potassium carbonate In water at 80℃; for 12h; Green chemistry; chemoselective reaction;	General procedure for O-arylation of phenols with aryl halides General procedure: To a stirred suspension of appropriate aryl halide(2.0 mmol) and phenol (2.0 mmol) in 6 ml water, Ni-alumina (0.125g, 6 mol % ofnickel metal) was added followed by K2CO3 (0.28 g, 2mmol) and SDS (0.04 g, 8 mol%). The reaction mixture was stirred for therequired period of time at 80°C till the reaction was complete (monitored withTLC). Then the reaction mixture was cooled to room temperature, ethyl acetate(20 mL) was added to dissolve the product and the catalyst was separated simplyby filtration. The residue (recovered catalyst) was thoroughly washed withEtOAc (4×5 mL) followed by water (2×10 mL). The aqueous reaction mixture was repeatedly extracted with ethyl acetate (3×5 mL). The combined organic extractswere washed with water (3× 10 mL) and dried over anhydrous Na2SO4.The crude product was obtained by removal of the solvent under reduced pressure which was furtherpurified by filtration chromatography on a short column of silica gel using1-4% ethyl acetate-hexane as eluent.
24%	With tetrabutylammomium bromide; caesium carbonate In N,N-dimethyl-formamide at 145℃; for 24h; Inert atmosphere;	2.3 General procedure for CuO-Fe₃O₄-catalyzed O-arylation of phenols with aryl halides General procedure: To a stirred solution of phenol (2.2mmol) in DMF (15.0mL) under an argon atmosphere were added CuO-Fe3O4 (0.2mmol), TBAB (0.2mmol), Cs2CO3 (326mg, 1.0mmol) and aryl halide (2.0mmol). The reaction mixture was stirred at the required temperature (145°C) for 24 h. At the end of reaction, the catalyst was removed by a magnet and the resulting mixture was quenched with water and extracted with EtOAc. The organic phases were dried over MgSO4, followed by evaporation under reduced pressure to remove the solvent. The residue was purified by column chromatography on silica gel to afford the desired product.

With potassium carbonate In acetone Reflux;

Reference： [1]Hajipour, Abdol R.; Khorsandi, Zahra; Fatemeh Mohammadi Metkazini [Journal of Organometallic Chemistry, 2019, vol. 899]
[2]Ghatak, Avishek; Khan, Sagar; Roy, Rimi; Bhar, Sanjay [Tetrahedron Letters, 2014, vol. 55, # 51, p. 7082 - 7088]
[3]Zhang, Ying-Peng; Shi, Ai-Hong; Yang, Yun-Shang; Li, Chun-Lei [Chinese Chemical Letters, 2014, vol. 25, # 1, p. 141 - 145]
[4]Location in patent: scheme or table Yi, Wei; Cao, Rihui; Chen, Zhiyong; Yu, Liang; Wen, Huan; Yan, Qin; Ma, Lin; Song, Huacan [Chemical and Pharmaceutical Bulletin, 2010, vol. 58, # 5, p. 752 - 754]

42
[ 14418-84-9 ]
[ 67-36-7 ]
[ 1245945-55-4 ]

Reference： [1]Chemistry - A European Journal,2010,vol. 16,p. 8984 - 8988

43
[ 67-36-7 ]
(4-phenoxyphenyl)methanamine monohydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-phenyloxybenzaldehyde With hydroxyamino hydrochloride In ethanol; lithium hydroxide monohydrate at 20℃; Stage #2: With hydrogenchloride; hydrogen In ethanol; lithium hydroxide monohydrate for 6h;	63 21.0 g of 4-phenoxybenzaldehyde, 10.5 g of hydroxylamine hydrochloride, 200 ml of ethanol and 10 ml of water were blended. The obtained mixture was stirred at a room temperature for 2 hours. Thereafter, the reaction mixture was left overnight. Subsequently, 10 ml of 10 N hydrochloric acid and 3.2 g of 10% palladium on carbon were added to the reaction mixture, and the obtained mixture was then stirred under an ordinary pressure in a hydrogen atmosphere for 6 hours. Thereafter, the reaction mixture was filtrated through Celite (registered trade mark), and the filtrate was then concentrated under reduced pressure. The residue was washed with water and chloroform, so as to obtain 19.3 g of 4-phenoxybenzylamine hydrochloride.4-phenoxybenzylamine hydrochloride [Show Image] 1H-NMR (DMSO-D6) δ: 3.99 (2H, s), 6.99-7.04 (4H, m), 7.14-7.9 (1H, m), 7.39-7.44 (2H, m), 7.52-7.56 (2H, m), 8.56 (3H, br s).
	Stage #1: 4-phenyloxybenzaldehyde With hydroxyamino hydrochloride In ethanol; lithium hydroxide monohydrate at 20℃; for 16h; Stage #2: With hydrogenchloride; palladium on activated charcoal; hydrogen In ethanol; lithium hydroxide monohydrate at 20℃; for 0.5h;	20.1 Step-1: Synthesis of (4-phenoxyphenyl)methanamine hydrochloride To a stirred solution of 4-phenoxybenzaldehyde (0.5 g, 2.5 mmol, 1.0 eq.) in EtOH:H2O (9:1 mL) was added Hydroxylammonium chloride (0.17 g, 2.5 mmol, 1.0 eq.) at RT. The resulting mixture stirred for 16 h. Following this, to the above mixture added 10N HCl (0.5 mL) and Pd-C (0.15 g) at RT. The resulting mixture stirred under Hydrogen balloon pressure for 30 min. Following is, reaction was filtered through celite pad, the celite pad washed with ethyl acetate the combined filtered dried over anhydrous Na2SO4, filtered and concentrated under vacuum to get the solid residue. The crude used for next step without purification (0.3 g, 60%). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.36 (s, 1H) 7.35-7.48 (m, 4H) 7.15 (t, J=7.24 Hz, 1H) 6.94-7.04 (m, 4H) 3.90 (s, 2H)
	Multi-step reaction with 3 steps 1: pyridine; hydroxyamino hydrochloride / ethanol / 24 h / 20 °C / Inert atmosphere; Reflux 2: lithium tetrahydridoborate / tetrahydrofuran / 72 h / 0 °C / Reflux; Inert atmosphere 3: hydrogenchloride / methanol / Inert atmosphere

Reference： [1]Current Patent Assignee: Sumitomo Chemical (w/o Dongwoo Fine-Chem); SUMITOMO CHEMICAL COMPANY LIMITED - EP2248423, 2010, A1 Location in patent: Page/Page column 261
[2]Current Patent Assignee: INTEGRAL BIOSCIENCES PRIVATE LTD - US2020/206233, 2020, A1 Location in patent: Paragraph 0313-0314
[3]Fanta, Claire C.; Tlusty, Kaitlyn J.; Pauley, Sarah E.; Johnson, Amanda L.; Benjamin, Genevieve A.; Yseth, Taylor K.; Bunde, Michaela M.; Pierce, Paul T.; Wang, Shirley; Vitiello, Peter F.; Mays, Jared R. [ChemMedChem, 2022, vol. 17, # 14]

44
[ 3167-50-8 ]
[ 67-36-7 ]
C₁₈H₁₃N₃O₃ [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2010,vol. 45,p. 5848 - 5855

45
[ 67-36-7 ]
[ 19493-09-5 ]
[ 4973-29-9 ]

Reference： [1]Advanced Synthesis and Catalysis,2010,vol. 352,p. 3190 - 3194

46
[ 67-36-7 ]
[ 109-89-7 ]
[ 95725-06-7 ]

Yield	Reaction Conditions	Operation in experiment
78%	Stage #1: 4-phenoxy benzaldehyde; diethylamine In tetrahydrofuran at -78 - 20℃; for 0.666667h; Inert atmosphere; Stage #2: With oxygen; potassium hexamethylsilazane In tetrahydrofuran; toluene at -78 - 20℃; for 3h;	4.4. Direct oxidative amidation of aryl aldehydes General procedure: Procedure A: To a round-bottom flask that was flame-dried and cooled under nitrogen were added THF (3 mL), aromatic aldehyde 67 (0.5 mmol), and amine 68 (2 mmol, 4 equiv). After stirring for 30 min at room temperature, the reaction system was cooled to -78 °C and after another 10 min, the flask was collected to an oxygen balloon, NaHMDS (2 M in THF, 0.75 mL, 1.5 mmol, 3 equiv) or KHMDS (0.5 M in toluene, 3 mL, 1.5 mmol, 3 equiv) was added dropwise via a syringe. The reaction mixture was then allowed to warm slowly to an indicated temperature. Upon completion at the indicated time, the reaction was quenched by addition of saturated NH4Cl (3 mL) and extracted with EtOAc (15 mL×2). The combined organic layer was washed by brine (15 mL) and dried over MgSO4. The solvent was removed under vacuum, and the residue was purified by flash chromatography on silica gel to give the amide product 69.

Reference： [1]Wang, Xinbo; Wang, David Zhigang [Tetrahedron, 2011, vol. 67, # 19, p. 3406 - 3411]

47
[ 67-36-7 ]
[ 348633-10-3 ]
[ 1313884-73-9 ]

Yield	Reaction Conditions	Operation in experiment
69%	Stage #1: 4-phenoxy benzaldehyde; 1-((1R,5S)-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)-N-methylmethanamine With sodium tris(acetoxy)borohydride In 1,2-dichloro-ethane at 20℃; for 20h; Stage #2: With sodium hydroxide In water; 1,2-dichloro-ethane for 0.166667h;	4.6. Procedure E: General procedure for reductive alkylation of compound 22 General procedure: Amine 22 (0.3 g, 1.8 mmol) and the aldehyde (1.0 mmol) were mixed with dry DCE (4 mL). Next, Na(AcO)3BH (0.53 g, 2.5 mmol) was added and the mixture was stirred at rt for 20 h. Aq NaOH-soln (1.0 M, ca. 10 mL) was added and the mixture was stirred vigorously for 10 min, after which DCM was added. The organic layer was separated and the aq layer was back-extracted with DCM (1×). The combined organic layers were dried (Na2SO4), filtered and concentrated. The crude product was purified by column chromatography.

Reference： [1]Wijtmans, Maikel; Verzijl, Dennis; Bergmans, Serge; Lai, Michael; Bosch, Leontien; Smit, Martine J.; De Esch, Iwan J.P.; Leurs, Rob [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 11, p. 3384 - 3393]

48
[ 67-36-7 ]
[ 145-13-1 ]
[ 1352081-19-6 ]

Yield	Reaction Conditions	Operation in experiment
72%	With sodium hydroxide In ethanol; water at 20℃; for 3h;	8.1. General procedure for benzylidene derivatives 2-17 General Procedure: The ethanol (25 mL) and NaOH (4 M, 3 mL) were mixed, cooled in an ice bath, and then compound 1 (0.3 mmol, 100 mg) was added. The aromatic aldehyde (0.6 mmol) was added dropwise. The mixture was stirred for three hrs, and then neutralized by adding 2 M HCl. The precipitates were filtered, washed with acidic water (10 mL x 2), and neutral water (20 mL), and dried in vacuum.

Reference： [1]Location in patent: experimental part Iqbal Choudhary; Shahab Alam; Atta-Ur-Rahman; Yousuf, Sammer; Wu, Yang-Chang; Lin, An-Shen; Shaheen [Steroids, 2011, vol. 76, # 14, p. 1554 - 1559]

49
[ 67-36-7 ]
[ 29921-15-1 ]

Yield	Reaction Conditions	Operation in experiment
36%	With nitromethane; trifluoromethylsulfonic anhydride; acetic acid In formic acid at 80 - 120℃;	55 Example 55 p-phenoxybenzamide Take a reaction tube and add 60-100mg (1.2mmol) of nitromethane, 50-70mg (0.3mmol) of p-phenoxybenzaldehyde, 0.5mL of acetic acid, 150-200mg (0.6mmol) of trifluoromethanesulfonic anhydride, and 30 of formic acid. -60mg (0.75mmol), stirred at 80-120°C for 1-72 hours. After the reaction was completed, 10 mL of sodium hydroxide solution was added to quench the reaction, extracted with ethyl acetate 3 times, the organic phase was washed with 5 mL of brine, and the organic phases were combined and separated by column chromatography to obtain 23 mg of p-phenoxybenzamide. The yield was 36%. .
36%	With formic acid; nitromethane; trifluoromethylsulfonic anhydride In acetic acid at 100℃; for 12h;
	With sodium amide

Reference： [1]Current Patent Assignee: PEKING UNIVERSITY - CN112574054, 2021, A Location in patent: Paragraph 0285-0288
[2]Jiao, Ning; Liu, Jianzhong; Qiu, Xu; Song, Song; Wei, Jialiang; Wen, Xiaojin; Zhang, Cheng; Zhang, Ziyao [Science, 2020, vol. 367, # 6475, p. 281 - 285]
[3]Location in patent: scheme or table Piri, Farideh; Ghaforinia, Nastaran; Taghavi, Mohammad; Karimian, Ramin [Asian Journal of Chemistry, 2010, vol. 22, # 2, p. 1403 - 1406]

50
[ 67-56-1 ]
[ 67-36-7 ]
[ 21218-94-0 ]

Yield	Reaction Conditions	Operation in experiment
80%	With dihydrogen peroxide; zinc dibromide In water at 20℃; for 16h;	8 General procedure for the ester synthesis: General procedure: In a 50 mL tube, ZnBr2 (10 mol %), and a stirring bar was added. Then H2O2 (4 mmol; 30% aq) was added slowly to the tube after the addition of aldehyde (1 mmol) and MeOH (4 mL) by syringe. Then keep the final solution at room temperature for 16 h. Hexadecane (100 mg) and ethyl acetate (3 mL) were injected, a part of the solution was taken for GC and GC-MS analysis after properly mixing. All the products are commercially available.
70%	With tetradecyl(tributyl)phosphonium methanesulfonate at 20℃; for 24h; Inert atmosphere; Electrolysis; Sealed tube; Green chemistry;

Reference： [1]Location in patent: experimental part Wu, Xiao-Feng [Tetrahedron Letters, 2012, vol. 53, # 26, p. 3397 - 3399]
[2]Yu, Congjun; Özkaya, Bünyamin; Patureau, Frederic W. [Chemistry - A European Journal, 2021, vol. 27, # 11, p. 3682 - 3687]

51
[ 67-36-7 ]
[ 3096-81-9 ]
[ 68-11-1 ]
[ 1380593-31-6 ]

Yield	Reaction Conditions	Operation in experiment
39%	With triethylamine; In methanol; for 12h;Reflux;	General procedure: A solution of the corresponding aromatic aldehyde (0.8-10.3 mmol), 2-sulfanylacetic acid (1.0-1.3 equiv) and the corresponding aromatic nitrile (1.0-1.3 equiv) and triethylamine (1.5-15.0 equiv) in methanol was refluxed over night. The reaction mixture was evaporated under reduced pressure and the crude product was recrystallized from ethanol and washed with acetone.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 3575 - 3583

52
[ 555-16-8 ]
[ 108-95-2 ]
[ 67-36-7 ]

Yield	Reaction Conditions	Operation in experiment
100%	With C₂₉H₂₆FeN₃Pd⁽¹⁺⁾*Cl^(1-); oxygen; Cs₂CO₃ In 1,4-dioxane; dimethyl sulfoxide at 100℃; for 24h;	4.2. General procedure for synthesis of 4-phenoxybenzaldehyde General procedure: A reaction vessel was charged with a mixture of phenylboronic acid (1.5mmol), Cs2CO3 (1.0mmol), catalyst Ic (1mol%) in dioxane/DMSO (1:1) (2.0mL), and stirred for about 20min under air. Then 4-nitrobenzaldehyde (0.5mmol) was then added. The mixture was heated to 100°C and incubated in an oil bath at 100°C for 24h under air. After the reaction was complete, the solvent was evaporated under reduced pressure. The product 3aa was obtained by purifying on preparative TLC, eluting with ethyl acetate/petroleum ether, and the yield was calculated based on the 4-nitrobenzaldehyde (the purified products were identified by NMR spectra and comparison of the melting points with the literature data).
97%	With [Pd((η5-C5H5)Fe[(η5-C5H3)C(Me)=N(C6H4-4-Me)])(μ-Cl)]2; Cs₂CO₃ In N,N-dimethyl-formamide at 100℃; for 4h;
97%	With palladium 10% on activated carbon; potassium carbonate In lithium hydroxide monohydrate; dimethyl sulfoxide at 100℃; for 6h;

94%	With 2C₁₅H₂₃N₃O₂2Cu⁽²⁺⁾4ClO₄^(1-)*5H₂O; potassium carbonate In ethanol at 80℃; for 3h; Green chemistry;
93%	With Cs₂CO₃ In N,N-dimethyl-formamide at 100℃; for 5h; Inert atmosphere; Schlenk technique; Green chemistry;	Heterogeneous copper-catalysed O-arylation of phenols by nitroarenes; general procedure General procedure: Under an argon atmosphere, a Schlenk tube was charged with MCM-41-2N-Cu(OAc)2(46 mg, 0.025 mmol), nitroarene 1 (0.5 mmol), phenol 2 (1.0 mmol), Cs2CO3 (1.0 mmol) and DMF (3 mL). The reaction mixture was stirred at 100 °C for 5 h under Ar. After being cooled to room temperature, the mixture was diluted with ethyl acetate (20 mL) and filtered. The MCM-41-2N-Cu(OAc)2 catalyst was washed with distilled water (2 × 5 mL), DMF (2 × 5 mL) and EtOH (2 × 5 mL) and could be reused in the next run. The filtrate was washed with water (2 × 10 mL) and dried over anhydrous MgSO4. After removal of the solvent under reduced pressure, the residue was purified by column chromatography (EtOAc/hexane) on silica gel to afford the desired product 3. 4-Phenoxybenzaldehyde (3a): Colourless oil; 22 1H NMR (400 MHz, CDCl3): δ 9.91 (s, 1H), 7.86-7.82 (m, 2H), 7.43-7.38 (m, 2H), 7.26-7.19 (m, 1H), 7.10-7.03 (m, 4H); 13C NMR (100 MHz, CDCl3): δ 190.8, 163.2, 155.1, 131.9, 131.3, 130.2, 124.9, 120.4, 117.6.
92%	With Cu(OAc)₂*H₂O; Cs₂CO₃ In N,N-dimethyl-formamide at 100℃; for 4h; Inert atmosphere; Schlenk technique;	4.2 General procedure for the synthesis of unsymmetrical diaryl ethers General procedure: Under N2 atmosphere, a Schlenk tube was charged with nitroarenes 1 (0.5 mmol), phenols 2 (1.0 mmol), Cu(OAc)2·H2O (5 mol %), and Cs2CO3 (1.0 mmol) in DMF (3 mL) at room temperature. After that, the mixture was stirred constantly at 100 °C (oil bath temperature) for 4 h. After the completion of the reaction, as monitored by TLC and GC-MS analysis, the reaction mixture was cooled to room temperature, diluted with ethyl acetate, and filtrated. The filtrate was concentrated under vacuum, and the resulting residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate) to afford the desired arylated product 3.
91%	With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 8h;
68%	With tripotassium phosphate tribasic; tetrabutylammonium bromide; nickel (II) chloride at 100℃; for 4h;	General procedure for the etherificationof nitrobenzenes with phenols/alcohols General procedure: A vessel was charged with nitrobenzene (0.5 mmol), phenol/alcohol (1 mmol), NiCl2(0.1 mmol), and K3PO4(2 mmol). To this mixture, was added TBAB (1.5 g) and heated to100 °C. Progress of the reaction was monitored by TLC.After completion of the reaction, silica gel (1 g) was addedto the reaction vessel and the mixture was added to a columnchromatography. Petroleum ether/ethylacetate (10:1)was used as the eluent to separate the desired product.
	With Cu₂(1,4-benzenedicarboxylate)₂(1,4-diazabicyclo[2.2.2]octane); potassium carbonate In N,N-dimethyl-formamide at 100℃; for 2h; Inert atmosphere;
	With potassium carbonate In N,N-dimethyl-formamide at 120℃; for 1h; Schlenk technique; Inert atmosphere;

Reference： [1]Peng, Dongpo; Yu, Ajuan; Wang, Hailei; Wu, Yangjie; Chang, Junbiao [Tetrahedron, 2013, vol. 69, # 33, p. 6884 - 6889]
[2]Wang, Hailei; Yu, Ajuan; Cao, Aijuan; Chang, Junbiao; Wu, Yangjie [Applied Organometallic Chemistry, 2013, vol. 27, # 10, p. 611 - 614]
[3]Begum, Tahshina; Mondal, Manoj; Borpuzari, Manash Protim; Kar, Rahul; Gogoi, Pradip K.; Bora, Utpal [European Journal of Organic Chemistry, 2017, vol. 2017, # 22, p. 3244 - 3248]
[4]Maity, Tanmoy; Saha, Debraj; Bhunia, Susmita; Brandão, Paula; Das, Soma; Koner, Subratanath [RSC Advances, 2015, vol. 5, # 100, p. 82179 - 82191]
[5]Du, Yingying; Yao, Fang; Tuo, Yuxin; Cai, Mingzhong [Journal of Chemical Research, 2017, vol. 41, # 12, p. 725 - 729]
[6]Chen, Jiuxi; Wang, Xingyong; Zheng, Xingwang; Ding, Jinchang; Liu, Miaochang; Wu, Huayue [Tetrahedron, 2012, vol. 68, # 43, p. 8905 - 8907]
[7]Maity, Tanmoy; Bhunia, Susmita; Das, Soma; Koner, Subratanath [RSC Advances, 2016, vol. 6, # 40, p. 33380 - 33386]
[8]Zamiran, Fatemeh; Ghaderi, Arash [Journal of the Iranian Chemical Society, 2019, vol. 16, # 2, p. 293 - 299]
[9]Phan, Nam T. S.; Nguyen, Tung T.; Nguyen, Vu T.; Nguyen, Khoa D. [ChemCatChem, 2013, vol. 5, # 8, p. 2374 - 2381]
[10]Chen, Huan; Chen, Junyi; Fu, Yu; Han, Jingrui; Shao, Lei; Yuan, Hehe; Zhang, Bing; Zhang, Yan; Zhou, Huazhang; Zhou, Jun [Inorganic Chemistry, 2022]

53
[ 67-36-7 ]
[ 64-04-0 ]
[ 329920-36-7 ]

Yield	Reaction Conditions	Operation in experiment
70%	With tert.-butylhydroperoxide; zinc dibromide In water at 80℃; for 16h;	Typical procedure for preparation of N-phenethylbenzamide 3a General procedure: In a glass pressure tube (25 mL), ZnBr2 (22.2 mg, 0.1 mmol), benzaldehyde 1a (106 mg, 1 mmol), 2-phenylethanamine 2a (133.1 mg, 1.1 mmol), and tert-butyl hydroperoxide 3a (270 mg, 3 mmol; 70% solution in water) were added successively. Next, the pressure tube was closed and the resulting mixture was stirred at 80 oC in an oil bath for 16 h. After cooling down to room temperature, the solvent was removed under vacuum. The residue was directly purified by flash chromatography on silica gel eluting with heptane : ethanol (15 : 1) to give N-phenethylbenzamide 3a as a white solid (176mg, 78%).

Reference： [1]Zhang, Min; Wu, Xiao-Feng [Tetrahedron Letters, 2013, vol. 54, # 9, p. 1059 - 1062]

54
[ 67-36-7 ]
[ 109-73-9 ]
[ 941242-81-5 ]

Yield	Reaction Conditions	Operation in experiment
75%	With tert.-butylhydroperoxide; zinc dibromide In water at 80℃; for 16h;	Typical procedure for preparation of N-phenethylbenzamide 3a General procedure: In a glass pressure tube (25 mL), ZnBr2 (22.2 mg, 0.1 mmol), benzaldehyde 1a (106 mg, 1 mmol), 2-phenylethanamine 2a (133.1 mg, 1.1 mmol), and tert-butyl hydroperoxide 3a (270 mg, 3 mmol; 70% solution in water) were added successively. Next, the pressure tube was closed and the resulting mixture was stirred at 80 oC in an oil bath for 16 h. After cooling down to room temperature, the solvent was removed under vacuum. The residue was directly purified by flash chromatography on silica gel eluting with heptane : ethanol (15 : 1) to give N-phenethylbenzamide 3a as a white solid (176mg, 78%).

Reference： [1]Zhang, Min; Wu, Xiao-Feng [Tetrahedron Letters, 2013, vol. 54, # 9, p. 1059 - 1062]

55
[ 555-16-8 ]
[ 98-80-6 ]
[ 67-36-7 ]
[ 1369528-52-8 ]

Yield	Reaction Conditions	Operation in experiment
1: 85% 2: 6%	With C₂₉H₂₆FeN₃Pd⁽¹⁺⁾*Cl^(1-); oxygen; caesium carbonate; <SUP>18</SUP>O-labeled water In 1,4-dioxane; dimethyl sulfoxide at 100℃; for 24h;	4.2. General procedure for synthesis of 4-phenoxybenzaldehyde General procedure: A reaction vessel was charged with a mixture of phenylboronic acid (1.5mmol), Cs2CO3 (1.0mmol), catalyst Ic (1mol%) in dioxane/DMSO (1:1) (2.0mL), and stirred for about 20min under air. Then 4-nitrobenzaldehyde (0.5mmol) was then added. The mixture was heated to 100°C and incubated in an oil bath at 100°C for 24h under air. After the reaction was complete, the solvent was evaporated under reduced pressure. The product 3aa was obtained by purifying on preparative TLC, eluting with ethyl acetate/petroleum ether, and the yield was calculated based on the 4-nitrobenzaldehyde (the purified products were identified by NMR spectra and comparison of the melting points with the literature data).

Reference： [1]Peng, Dongpo; Yu, Ajuan; Wang, Hailei; Wu, Yangjie; Chang, Junbiao [Tetrahedron, 2013, vol. 69, # 33, p. 6884 - 6889]

56
[ 67-36-7 ]
[ 96-34-4 ]
C₁₆H₁₄O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With sodium hydride In tetrahydrofuran; mineral oil at 20℃;	10 Synthesis of KOK2019 (Step 10) To sodium hydride (60%) (303 mg, 7.57 mmol), tetrahydrofuran (5 ml) was added and stirred. To this, a mixture solution of 4-phenoxy benzaldehyde (1.00 g, 5.05 mmol), methyl chloroacetate (657 mg, 6.05 mmol) and tetrahydrofuran (10 ml) was added dropwise and stirred at room temperature overnight. The reaction solution was ice-cooled, neutralized with 1M sulfuric acid, extracted three times with dichloromethane, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Thereafter, the residue was purified by silica gel column chromatography (hexane : ethyl acetate = 10 : 1) to obtain the titled compound (white crystal: 940 mg, 69%). 1H-NMR (CDCl3, 270 MHz) δ ppm: 3.52 (1H, d, J = 1.6 Hz), 3.83 (3H, s), 4.08 (1H, d, J = 1.6 Hz), 6.94-7.04 (4H, m), 7.08-7.17 (1H, m), 7.20-7.28 (2H, m), 7.28-7.40 (2H, m).

Reference： [1]Current Patent Assignee: NATIONAL AGRICULTURE AND FOOD RESEARCH ORGANIZATION; INSTITUTE OF PHYSICAL AND CHEMICAL RESEARCH (RIKEN); YOKOHAMA CITY UNIVERSITY - EP2682383, 2014, A1 Location in patent: Paragraph 0127; 0128; 0129

57
[ 1438-16-0 ]
[ 67-36-7 ]
[ 366809-01-0 ]

Yield	Reaction Conditions	Operation in experiment
1.52 g	With piperidine; In ethanol; for 2h;Reflux;	Preparation Example 2 To a solution of <strong>[1438-16-0]3-aminorhodanine</strong> (1.00 g) in ethanol (20 ml) were added 4-phenoxybenzaldehyde (1.47 g) and piperidine (57 mg), and the mixture was heated with reflux for 2 hr. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: chloroform) to give 3-amino-5-(4-phenoxybenzylidene)-2-thioxothiazolidin-4-one (1.52g).

Reference： [1]Patent: US2014/194412,2014,A1 .Location in patent: Paragraph 0757; 0758

58
[ 591-50-4 ]
[ 123-08-0 ]
[ 67-36-7 ]

Yield	Reaction Conditions	Operation in experiment
74%	With sodium dodecyl-sulfate; potassium carbonate In water at 80℃; for 12h; Green chemistry; chemoselective reaction;	General procedure for O-arylation of phenols with aryl halides General procedure: To a stirred suspension of appropriate aryl halide(2.0 mmol) and phenol (2.0 mmol) in 6 ml water, Ni-alumina (0.125g, 6 mol % ofnickel metal) was added followed by K2CO3 (0.28 g, 2mmol) and SDS (0.04 g, 8 mol%). The reaction mixture was stirred for therequired period of time at 80°C till the reaction was complete (monitored withTLC). Then the reaction mixture was cooled to room temperature, ethyl acetate(20 mL) was added to dissolve the product and the catalyst was separated simplyby filtration. The residue (recovered catalyst) was thoroughly washed withEtOAc (4×5 mL) followed by water (2×10 mL). The aqueous reaction mixture was repeatedly extracted with ethyl acetate (3×5 mL). The combined organic extractswere washed with water (3× 10 mL) and dried over anhydrous Na2SO4.The crude product was obtained by removal of the solvent under reduced pressure which was furtherpurified by filtration chromatography on a short column of silica gel using1-4% ethyl acetate-hexane as eluent.
	With potassium carbonate In N,N-dimethyl-formamide at 110℃; for 24h; Inert atmosphere;	2.8. General procedure for O-arylation of phenol with aryl halides catalyzed by CuNPsQ-POP(7.3 % Cu) General procedure: In a typical reaction in a 25 mL round bottom flask (two neckedflask)a mixture of aryl halide (1 mmol), phenol (1.2 mmol), K2CO3 (2mmol), DMF (2 mL) and CuNPsQ-POP(7.3 % Cu) catalyst (75 mg) wasstirred under nitrogen atmosphere at 110 °C for 24. After the reaction,ethyl acetate (10 mL) was added to the reaction mixture and the catalystwas separated by filtration and washed with ethyl acetate. After water(10 mL) was added to the filtrate, extracted with ethyl acetate (2 × 10mL) and the organic phase was dried with anhydrous MgSO4. Theorganic phase was analyzed by GC to determine conversion and selectivity.Then the solvent was removed under reduced pressure and thecrude product was purified by column chromatography over silica gel toobtain the desired product. The product was analyzed by 1H-NMR and13C-NMR.

Reference： [1]Ghatak, Avishek; Khan, Sagar; Roy, Rimi; Bhar, Sanjay [Tetrahedron Letters, 2014, vol. 55, # 51, p. 7082 - 7088]
[2]Gorginpour, Forough; Zali-Boeini, Hassan [Molecular catalysis, 2021, vol. 504]

59
[ 67-36-7 ]
[ 17396-35-9 ]
(3Z,5Z)-3,5-bis[(4-phenoxyphenyl)methylene]tetrahydro-4H-thiopyran-4-one 1,1-dioxide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 1691 - 1704

60
[ 61-54-1 ]
[ 67-36-7 ]
N-[2-(1H-indol-3-yl)ethyl]-4-phenoxybenzenecarbothioamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With sulfur In N,N-dimethyl-formamide at 110℃; for 1h;	General Procedure for the Synthesis of N_b-Thioacyltryptamines (1a-r). General procedure: Tryptamine (7)(0.60 g, 3.75 mmol), the appropriate aldehyde (8a-r, 2.50 mmol) and elemental sulfur(0.20 g, 6.25 mmol) in dry DMF (10 mL) were stirred at 110 °C for 1 h. Aftercooling, the reaction mixture was concentrated under reduced pressure. Theresidue was purified by flash column chromatography on silica gel (Merck 107736silica gel 60 H, hexane-CH2Cl2or CH2Cl2-MeOH)to afford products 1a-r.

Reference： [1]Milen, Mátyás; Slégel, Péter; Keglevich, Péter; Keglevich, György; Simig, Gyula; Volk, Balázs [Tetrahedron Letters, 2015, vol. 56, # 42, p. 5697 - 5700]

61
[ 91-63-4 ]
[ 67-36-7 ]
C₂₃H₁₇NO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With Fe<SUB>3</SUB>O(biphenyl-4,4'-dicarboxylate)<SUB>3</SUB>; acetic acid In toluene at 120℃; for 24h; Inert atmosphere;	2.3. Catalytic studies General procedure: In a typical experiment, Fe3O(BPDC)3catalyst (0.012 g, 10 mol%)was added to the 10 ml vial containing a solution of 2-methylquinoline (0.057 g, 0.4 mmol), acetic acid (0.002 g, 10 mol%),benzaldehyde (0.064 g, 0.6 mmol) and diphenyl ether (0.068 g,0.4 mmol) as an internal standard in toluene (1 ml). The catalystamount was calculated with respect to the iron/2-methylquinolinemolar ratio and the measured AAS value of Fe3O(BPDC)3(See Sup-porting Information). Then reaction mixture was filled with argonand magnetically stirred for 24 h at 120C. Reaction yield wasmonitored by withdrawing aliquots from the reaction mixture,quenching with Na2CO3solution (1 ml). The organic componentswere then extracted into ethyl acetate (3 ml), dried over anhy-drous Na2SO4, and analyzed by GC with reference to diphenyl ether.The combined organic layers were concentrated under reducedpressure. The resulting residue was purified by recrystalizationin ethanol and water to afford (E)-2-styrylquinoline. The productidentity was further confirmed by GC-MS,1H NMR, and13C NMR.To investigate the recyclability of the Fe3O(BPDC)3, the catalystwas separated from the reaction mixture by simple centrifugation,washed with copious amounts of toluene, dichloromethane, thenactivated under vacuum at 150C for 3 h, and reused under identicalconditions.

Reference： [1]Dang, Hang T.; Lieu, Thien N.; Truong, Thanh; Phan, Nam T.S. [Journal of Molecular Catalysis A: Chemical, 2016, vol. 420, p. 237 - 245]

62
[ 1745-07-9 ]
[ 67-36-7 ]
C₂₄H₂₅NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50.1%	With sodium tris(acetoxy)borohydride; In ethyl acetate; at 20 - 30℃;Inert atmosphere;	In a 25 ml round-bottom flask compound is added in 32A (322 mg, 1 . 67mmol), compound 32B (300 mg, 1 . 52mmol), ethyl acetate (2 ml), stirring, add three acetoxy nabh (386 mg, 1 . 83mmol). Stir at room temperature overnight, TLC detection raw material the reaction is complete. Saturated sodium bicarbonate aqueous solution for quenching the reaction, then using ethyl acetate extraction, combined with the organic layer, dry anhydrous sodium sulfate, concentrated after the silica gel column chromatography, with petroleum ether: ethyl acetate (5:1) as eluant, get white solid product 32 (286 mg, yield: 50.1%).

Reference： [1]Patent: CN105777632,2016,A .Location in patent: Paragraph 0405; 0406; 0407

63
[ 3096-81-9 ]
[ 67-36-7 ]

Yield	Reaction Conditions	Operation in experiment
82%	With diisobutylaluminium hydride; at -70 - 20℃;Inert atmosphere;	General procedure: To a round bottom flask containing THF, the appropriate aryl nitrileanalogue (1.0 equiv.) was added followed by the addition of nitrogengas. Next, the solution was cooled to 70 C before the addition of aDIBAL-H (1.1 equiv.) solution (1.0 M in THF). After, the mixture wasstirred at 40 C for 5 h under nitrogen until TLC indicated the startingmaterial had been fully consumed. Subsequently, the reaction vessel wasplaced in an ice bath and quenched with 1 mL ethyl acetate and 20 mLHCl (1.0 M). After, the resulting solution was partitioned between EtOAcand brine. Using additional EtOAc, the aqueous brine solution waswashed three times and the combined organic layers were dried overNa2SO4, filtered, and concentrated via vacuum. The resulting concentratewas purified by silica gel chromatography.4.2.6.1. 4-phenoxybenzaldehyde (15a). White solid, yield 82%. 1H NMR(400 MHz, CDCl3) δ: 9.92 (s, 1H), 7.84 (d, J = 8.8 Hz, 2H), 7.46 - 7.37(m, 2H), 7.23 (t, J = 7.4 Hz, 1H), 7.09 (dd, J = 8.7, 1.1 Hz, 2H), 7.06 (d,J = 8.4 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ: 190.9, 163.3, 155.2,132.1, 131.4, 130.3, 125.1, 120.5, 117.7. HRMS (ESI + ) [M + H]+ calcdfor C13H11O2: 199.0754, found: 199.0753.

Reference： [1]Bioorganic and Medicinal Chemistry,2021,vol. 30
[2]ChemMedChem,2016,p. 2194 - 2204

64
[ 67-36-7 ]
[ 36881-42-2 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-phenoxy benzaldehyde With sodium tetrahydroborate In ethanol at 20℃; for 1h; Stage #2: With phosphorus tribromide at 20℃; for 1h;

Reference： [1]Wu, Xi-Shan; Wang, Rui; Xing, Yan-Li; Xue, Xiao-Qian; Zhang, Yan; Lu, Yong-Zhi; Song, Yu; Luo, Xiao-Yu; Wu, Chun; Zhou, Yu-Lai; Jiang, Jian-Qin; Xu, Yong [Acta Pharmacologica Sinica, 2016, vol. 37, # 11, p. 1516 - 1524]

65
[ 101-55-3 ]
[ 68-12-2 ]
[ 67-36-7 ]

Reference： [1]Organic Letters,2016,vol. 18,p. 6428 - 6431

66
[ 67-36-7 ]
C₁₃H₁₈N₄O₇ [ No CAS ]
C₂₆H₂₆N₄O₈ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With acetic acid In ethanol at 20℃; for 0.5h;	Chemical synthesis General procedure: Compound IV (2.50 mmol), phenyl aldehyde (2.75 mmol), and 30 μL acetic acid were added into 50 mL ethanol, and the reaction mixture was stirred at room temperature for 0.5 h. Crude products were purified by flash chromatography (Vpetroleumether/Vethylacetate=1:1) to obtain the compound 1.

Reference： [1]Chen, Qi; Zhang, Ji-Wei; Chen, Lu-Lu; Yang, Jun; Yang, Xin-Ling; Ling, Yun; Yang, Qing [Chinese Chemical Letters, 2017, vol. 28, # 6, p. 1232 - 1237]

67
[ 67-36-7 ]
[ 107622-80-0 ]

Yield	Reaction Conditions	Operation in experiment
75%	With hydroxylamine hydrochloride; In ethanol; water; at 20℃;Inert atmosphere;	A solution of 4-phenoxybenzaldehyde (2.0 g, 10 mmol), hydroxylamine hydrochloride (700 mg, 10 mmol), EtOH (20 ml), and water (1 ml) was stirred at room temperature overnight. To the reaction mixture were added 10 N Hci (1 ml) and of Pd/C (10% on carbon, 320 mg) and was stirred under hydrogen for 30 min. The reaction mixture was filtrated through Celite and concentrated to dryness. The residue was purified by flash column chromatography to give the title compound as a white solid (1.5 g, 75% yield).
75%		A solution of 4-phenoxybenzaldehyde (2.0 g, 10 mmol), hydroxylamine hydrochloride (700 mg, 10 mmol), EtOH (20 ml), and water (1 ml) was stirred at room temperature overnight. To the reaction mixture were added 10 N HCl (1 ml) and of Pd/C (10%on carbon, 320 mg) and was stirred under hydrogen for 30 min. The reaction mixture was filtrated through Celite and concentrated to dryness. The residue was purified by flash column chromatography to give the title compound as a white solid (1.5 g, 75% yield).

Reference： [1]Patent: WO2017/100668,2017,A1 .Location in patent: Page/Page column 164
[2]Patent: WO2018/103058,2018,A1 .Location in patent: Page/Page column 164

68
[ 3027-05-2 ]
[ 67-36-7 ]
1-acetyl-3-(4-phenoxybenzylidene)piperazine-2,5-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 3h;	General procedure: To 1,4-diacetylpiperazine-2,5-dione 1 (1.5 equiv.) in anhydrous DMF, the arylaldehyde 2 (1 equiv.) in presence of Cs2CO3 (1.5 equiv.) was added. The mixture was stirred at room temperature for about 3 h then poured into ice-cold water. The formed solid was then filtered, washed with cooled water and dried in vacuum to afford a solid residue, which was purified by precipitation in a mixture (Petroleumether/EtOAc) to yield corresponding diketopiperazines 3a-p.

Reference： [1]Medicinal Chemistry,2017,vol. 13,p. 744 - 752

69
[ 2010-15-3 ]
[ 67-36-7 ]
(5Z)-5-(4-phenoxybenzylidene)-3-phenyl-2-thioxoimidazolidin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With piperidine In ethanol Reflux;	1.1.2. General procedure for the synthesis of (5Z)-5-arylidene-3-aryl-2-thioxoimidazolidin-4-ones 3a-3h General procedure: A mixture of 3-aryl-2-thioxoimidazolidin-4-ones 1 or 2 (2.6 mmol), the appropriately substituted benzaldehyde (2.6 mmol) and piperidine (2.1 mmol) in ethanol (20 ml) was refluxed for 4-5 hours until the reagent disappearance. The reaction mixture was cooled and poured into water acidified with AcOH (pH 3-4). The precipitate was separated by filtration, washed with water and dried. The crystallization from methanol of the crude product provided compounds 3.
	With piperidine In ethanol Reflux;	4.1.2 General procedure for the synthesis of (5Z)-3-aryl-5-arylidene-2-thioxo-4-imidazolidinones (7a-w) General procedure: A mixture of 3-aryl-2-thioxo-4-imidazolidinone 8 (2.6mmol), the appropriate arylaldehyde (2.6mmol) and piperidine (2.1mmol) in ethanol (20ml) was refluxed for 4-5h until the reagent disappearance. The reaction mixture was cooled and poured into water acidified with AcOH (pH 3-4). The precipitate was separated by filtration, washed with water and dried. The crystallization from methanol of the crude product provided pure compounds 7.

Reference： [1]Maccari, Rosanna; Ettari, Roberta; Adornato, Ilenia; Naß, Alexandra; Wolber, Gerhard; Bitto, Alessandra; Mannino, Federica; Aliquò, Federica; Bruno, Giuseppe; Nicolò, Francesco; Previti, Santo; Grasso, Silvana; Zappalà, Maria; Ottanà, Rosaria [Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 3, p. 278 - 283]
[2]Ottanà, Rosaria; Paoli, Paolo; Lori, Giulia; Adornato, Ilenia; Previti, Santo; Naß, Alexandra; Wolber, Gerhard; Maccari, Rosanna [Bioorganic Chemistry, 2019, vol. 92]

70
[ 7025-19-6 ]
[ 67-36-7 ]
[ 1348470-80-3 ]

Yield	Reaction Conditions	Operation in experiment
83%	With sodium acetate; acetic acid; at 105℃;Inert atmosphere;	General procedure: To a mixture of aldehyde (1.0 mmol), <strong>[7025-19-6]3-(4-oxo-2-thioxothiazolidin-3-yl)propanoic acid</strong> (205 mg,1.0 mmol) or 3-(2-(1H-tetrazol-5-yl)ethyl)-2-thioxothiazolidin-4-one (229 mg, 1.0 mmol) and NaOAc (820 mg, 10.0 mmol) was added acetic acid (5.0 mL). The reaction was allowed to stir at 105 C for 0.5h - 12h, then cooled to room temperature. To the reaction was added water (15mL). The resulting mixture was sonicated to give yellow-orange slurry. After filtration, the solid was washed with water (75 mL) and dried under high vacuum to yield the corresponding product as a red fine powder.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 1024 - 1029

71
[ 503-87-7 ]
[ 67-36-7 ]
(Z)-5-(4-phenoxybenzylidene)-2-thioxoimidazolidin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With sodium acetate In acetic acid Reflux;	3.1.1. General Procedure to Obtain 5-Arylidenethiohydantoin (21, 23 and 24) General procedure: Thiohydantoin (2.90±5.80 g, 25±50 mmol), acetic acid (25±50 ml), sodium acetate (8.33±16.67 g,100-200 mmol) with appropriate arylidene aldehyde (25-50 mmol) in flat-bottom flask were heated in boiling point for 4±6 h and then mixed for 20 h. Reaction was controlled by TLC-chloroform/ethylacetate: 1/1. If necessary, purification was performed using crystallization from acetone or acetic acid.
	With sodium acetate; acetic acid Reflux;

Reference： [1]Kaczor, Aneta; Witek, Karolina; Podlewska, Sabina; Czekajewska, Joanna; Lubelska, Annamaria; Zesławska, Ewa; Nitek, Wojciech; Latacz, Gniewomir; Alibert, Sandrine; Pagès, Jean-Marie; Karczewska, Elzbieta; Kieć-Kononowicz, Katarzyna; Handzlik, Jadwiga [Molecules, 2019, vol. 24, # 3]
[2]Handzlik, Jadwiga; Kaczor, Aneta; Kincses, Annamária; Latacz, Gniewomir; Nové, Márta; Spengler, Gabriella; Szymánska, Ewa [Molecules, 2020, vol. 25, # 9]

72
[ 1001-53-2 ]
[ 67-36-7 ]
[ 38622-91-2 ]
N-(2-(5-(4-phenoxyphenyl)-1H-imidazol-1-yl)ethyl)acetamide [ No CAS ]

Reference： [1]MedChemComm,2016,vol. 7,p. 409 - 419

73
[ 67-36-7 ]
[ 62-53-3 ]
[ 446065-11-8 ]
N-(cyclohexyl(4-phenoxyphenyl)methyl)aniline [ No CAS ]

Reference： [1]Organic Letters,2019,vol. 21,p. 4853 - 4858

74
[ 67-36-7 ]
[ 1826-67-1 ]
1-(4-phenoxyphenyl)prop-2-en-1-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	In tetrahydrofuran at -78 - 20℃; for 16h; Inert atmosphere; Sealed tube;
88%	Stage #1: 4-phenoxy benzaldehyde; vinyl magnesium bromide In tetrahydrofuran at 20℃; for 20h; Stage #2: With water
	In tetrahydrofuran at -30 - 20℃; for 1h; Inert atmosphere;

In tetrahydrofuran Cooling; Inert atmosphere;

2. The synthesis and characterization of racemic allylic alcohols General procedure: To a stirred solution of aldehyde (10.0 mmol) in dry THF (10 mL), Grignard reagent (12.0 mmol) inTHF solution (1 M, 12 mL) was slowly added at -30 oC under nitrogen. Then the mixture was stirredat -30 oC for 1 h. The resulting solution was quenched with NH4Cl aqueous solution (5 mL), and thenextracted by ethyl acetate, dried over Na2SO4 and concentrated under reduce pressure. The crudeproduct was purified by silica flash chromatography (eluted with hexane/EtOAc) to give racemicallylic alcohols. Compounds (±)-1, 3, 5-10, 12-15, 17, 192 and (±)-185 were known. Characterizationof compounds (±)-11 and (±)-16 were described below in detail.

Reference： [1]Latham, Daniel E.; Polidano, Kurt; Williams, Jonathan M. J.; Morrill, Louis C. [Organic Letters, 2019, vol. 21, # 19, p. 7914 - 7918]
[2]Beller, Matthias; Ge, Yao; Huang, Weiheng; Jackstell, Ralf; Liu, Jiawang; Neumann, Helfried; Yang, Ji [Angewandte Chemie - International Edition, 2020, vol. 59, # 46, p. 20394 - 20398][Angew. Chem., 2020, vol. 132, # 46, p. 20574 - 20578,5]
[3]Chang, Xiaoyong; Chen, Fumin; He, Dongxu; Jin, Ming Yu; Pan, Yupeng; Xing, Xiangyou; You, Yipeng [Organic Letters, 2020, vol. 22, # 18, p. 7278 - 7283]
[4]Jin, Ming Yu; Tao, Guanyu; Xing, Xiangyou; You, Yipeng [Molecules, 2021, vol. 26, # 24]

75
[ 67-36-7 ]
[ 73183-34-3 ]
[ 269410-26-6 ]

Reference： [1]Chemistry - A European Journal,2020,vol. 26,p. 423 - 427

76
[ 110-91-8 ]
[ 67-36-7 ]
[ 536-74-3 ]
4-[1-(4-phenoxyphenyl)-3-phenylprop-2-yn-1-yl]morpholine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With malachite In toluene at 110℃; for 20h; Green chemistry;	General procedure for the preparation of propargylamines 4. General procedure: The appropriate aldehyde (2.0 mmol), amine (2.0 mmol) and alkyne (2.4 mmol) was dissolved in toluene (10 mL), then malachite (5 mg) was added to this solution. The mixture was heated to 110 °C and stirred for 20 h. The solvent was then evaporated under reduced pressure and the residue was purified by flash column chromatography.

Reference： [1]Milen, Mátyás; Györke, Gábor; Dancsó, András; Volk, Balázs [Tetrahedron Letters, 2020, vol. 61, # 10]

77
[ 15164-44-0 ]
[ 108-95-2 ]
[ 67-36-7 ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium hydroxide In neat (no solvent) at 90℃; for 7h; Green chemistry;	2.8 Typical Procedure for C-O Cross-Coupling Reaction General procedure: A round bottom glass tube was charged by phenol (1mmol,0.094g), iodobenzene (1mmol, 0.203g), NaOH (3mmol,0.12g), and Fe3O4AMCA-MIL53(Al)-NH2-CoII NPs(VI)(1.08mol%, 0.04g). The reaction mixture was stirred at 90°C under solvent free conditions. Thin layer chromatography(TLC) or gas chromatography (GC) were used to monitor the progress of the reaction. After completion of the reaction (6h), the reaction mixture was quenched by additionof 2mL ethyl acetate. The nanostructured catalyst was separated using an external magnetic field, washed with ethanol and water before drying in an oven at 50°C overnight for the next run use. The obtained crude product was purified by thin layer chromatography using n-hexane/ethyl acetate(50:1) to aford the pure diphenyl ether (0.161g, 95% yield).

Reference： [1]Mohammadinezhad, Arezou; Akhlaghinia, Batool [Catalysis Letters, 2020, vol. 150, # 2, p. 332 - 352]

78
potassium 4-methyl-1-phenyl-2,6,7-trioxa-1-borabicyclo-[2.2.2]octan-1-uide [ No CAS ]
[ 555-16-8 ]
[ 67-36-7 ]

Yield	Reaction Conditions	Operation in experiment
95%	With Oxone; copper diacetate; caesium carbonate In dimethyl sulfoxide at 100℃; for 24h;	1 Example 1 At room temperature, add the aromatic heterocyclic borate compound 1a of the above formula to the reaction flaskp-nitrobenzaldehyde compound 2a, catalyst Cu(OAc)2, additive Oxone, base Cs2CO3, reaction solvent DMSO.Among them, the molar ratio of 1a to 2a compound is 1:2, and the molar ratio of 1a to catalyst Cu(OAc)2 is 1:0.05 (or 1:0.1 or 1:0.2),The molar ratio of 1a to the additive Oxone is 1:1, the molar ratio of 1a to the base Cs2CO3 is 1:2.5, and the molar ratio of 1a to the reaction organic solvent is approximately 1:150.Stir and heat to 100°C under air conditions, and react for 24 hours.After the reaction was completed, water was added to quench the reaction, then the crude product was extracted with ethyl acetate, and the organic layers were combined.Anhydrous Na2SO4 was dried, evaporated to dryness under reduced pressure, and after separation and purification, the corresponding product 3a was obtained.The yield is 92% (1a:Cu(OAc)2=1:0.05) or 94% (1a:Cu(OAc)2=1:0.1) or 95% (1a:Cu(OAc)2=1:0.2 ).

Reference： [1]Current Patent Assignee: SHAOGUAN UNIVERSITY - CN111138259, 2020, A Location in patent: Paragraph 0055-0062

79
[ 672-89-9 ]
[ 67-36-7 ]
(E)-4-methoxy-6-(4-phenoxystyryl)-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
22%	With magnesium methanolate In methanol for 20h; Reflux; Inert atmosphere;	General Procedure for Preparation of Kavalactone Analogues 1-19. General procedure: Kavalactone analogues were prepared according to the previously reported method [24]. Amixture of 4-methoxy-6-methyl-pyran-2-one (25 mg, 0.178 mmol) and appropriate aldehyde (0.178mmol) in dimethoxymagnesium solution (60% in 2 mL methanol) was heated to reflux under anitrogen atmosphere for 20 h. After the reaction was completed, the mixture was concentrated underreduced pressure. The crude product was purified by flash column-chromatography (0%-40%EtOAc/cHexane) to give the title compound.

Reference： [1]Chang, Bill C. H.; Dilrukshi Herath, H. M. P.; Garcia-Bustos, José; Gasser, Robin B.; Hofmann, Andreas; Jabbar, Abdul; Ma, Guangxu; Nguyen, Nghi; Sleebs, Brad E.; Taki, Aya C.; Wang, Tao [Molecules, 2020, vol. 25, # 8]

80
[ 67-36-7 ]
1-(difluoromethyl)-4-phenoxybenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With potassium fluoride; diphenyl sulfide; Selectfluor In toluene; acetonitrile at 110℃; for 6h; Sealed tube; Inert atmosphere;	General procedure for deoxydifluorination of aldehydes General procedure: Into a sealed tube was added aldehyde 1 (0.4 mmol), KF (35 mg,0.6 mmol), Selectfluor (425 mg, 1.2 mmol), CH3CN/PhCH3 (1 mL/1 mL) and Ph2S (112 mg, 0.6 mmol) under a N2 atmosphere. The tube was sealed and the reaction mixture was stirred at 110 C for6 h. Water (10 mL) was added to quench the reaction, and the product was extracted with CH2Cl2 (10 mL 3). The combined organic phase was dried with Na2SO4 and then concentrated under reduced pressure. The residue was subjected to flash column chromatography to afford the desired product 3.
	With (bis-(2-methoxyethyl)amino)sulfur trufluoride In ethanol; dichloromethane at 20 - 65℃; for 24h; Inert atmosphere; Schlenk technique;

Reference： [1]He, Guowen; Xiao, Xuan; Jin, Han-Zhou; Lin, Jin-Hong; Zhong, Tongsheng; Zheng, Xing; Xiao, Ji-Chang [Tetrahedron, 2021, vol. 83]
[2]Bo, Zhi-Yu; Chen, Lin; Gao, Tian-Yu; Jing, Ke; Lan, Yu; Liu, Shi-Han; Luo, Shu-Ping; Yan, Si-Shun; Yu, Bo; Yu, Da-Gang [Chem, 2021, vol. 7, # 11, p. 3099 - 3113]

81
[ 719-98-2 ]
[ 67-36-7 ]
S-(trifluoromethyl) 4-phenoxybenzothioate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With disodium hydrogenphosphate; tetrakis(tetrabutylammonium)decatungstate(VI); In acetonitrile; at 20.0℃; for 96.0h;Inert atmosphere; Sealed tube; Irradiation;	General procedure: To a 8 mL glass vial was added TBADT (54.4 mg, 0.016 mmol, 8 mol %), aldehydes (0.2 mmol, 1.0 equiv), 6a (148.3 mg, 0.6 mmol, 3.0 equiv), Na2HPO4 (42.6 mg, 0.3 mmol, 1.5 equiv) and 0.5mL of CH3CN. The reaction mixture was degassed by bubbling with Ar for 15 s with an outlet needle and the vial was sealed with PTFE cap. The mixture was then stirred rapidly and irradiated with a 390 nm Blue LED (approximately 2 cm away from the light source) at room temperature for 96 h. Purification of the crude product by flash chromatography on silica gelusing the indicated solvent system afforded the desired product.

Reference： [1]Chinese Chemical Letters,2021,vol. 32,p. 3027 - 3030

82
[ 67-36-7 ]
[ 32004-66-3 ]
2-[(1Z)-5-fluoro-2-methyl-1-[(4-phenoxyphenyl)methylidene]-1H-inden-3-yl]acetic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With sodium methylate In methanol at 80℃; for 4h;
	In methanol at 80℃;	6 General procedure: To a solution ofindene 13 (1 eq. ) and aldehyde 14 (2.5 eq. ) in MeOH (12 L/mol) was added a base (e.g., MeONa) (3 eq. ) . After stirred at 80 overnight, the reaction was quenched with 1N HCl to a pH below 7, and the reaction mixture was extracted with EtOAc and washed by brine. The organic layers were combined, dried over anhydrous sodium sulfate, and then concentrated in vacuo to yield a crude product, which was purified by column chromatography to yield a compound of Formula (IX) .

Reference： [1]Huang, Fengyu; Zeng, Zhiping; Zhang, Weidong; Yan, Zhiqiang; Chen, Jiayun; Yu, Liangfa; Yang, Qian; Li, Yihuan; Yu, Hongyu; Chen, Junjie; Wu, Caisheng; Zhang, Xiao-kun; Su, Ying; Zhou, Hu [European Journal of Medicinal Chemistry, 2021, vol. 222]
[2]Current Patent Assignee: NUCMITO PHARMACEUTICALS - WO2021/249529, 2021, A1 Location in patent: Paragraph 00328-00329

83
[ 67-36-7 ]
[ 101-84-8 ]

Yield	Reaction Conditions	Operation in experiment
86%	With 1.26 wt% Ni(0) nanospecies supported on CeO₂ In toluene at 150℃; Inert atmosphere;

Reference： [1]Matsuyama, Takehiro; Yatabe, Takafumi; Yabe, Tomohiro; Yamaguchi, Kazuya [ACS Catalysis, 2021, vol. 11, # 22, p. 13745 - 13751]

84
[ 67-36-7 ]
[ 89524-99-2 ]
C₁₈H₁₇NO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94.6%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 5 - 15℃; for 2h;	1 Example 1: Synthesis of compound 6 To a round-bottom flask were added compound 1 (134.0 g), compound 2 (212.3 g) and DCM (675 mL). DBE1 (133.8 g) was added dropwise at 5~15°C. After 2 h, the reaction mixture was quenched with EbO. Acetic acid was added to adjust pH=6~7. The layers were separated. The aqueous phase was extracted with DCM twice. The organic phases were combined and concentrated. The mixture was added MTBE and stirred at room temperature for 1 h. The suspension was filtered to give compound 3 as an off-white solid (199.2 g, 94.6% yield, 96.0% purity). NMR (400 MHz, CDCh) d 7.47 - 7.35 (m, 2H), 7.40 - 7.34 (m, 4H), 7.22 - 7.13 (m, 1H), 7.06 - 7.02 (m, 2H), 6.98 - 6.92 (m, 2H), 3.82 (s, 3H), 2.12 (s, 3H).Mass: [M+H]+: 312.3;
94.6%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 5 - 15℃; for 2h;	2 Synthesis of methyl 2-acetamido-3-(4-phenoxyphenyl) propionate (6) 134.0 g of compound 3 and 212.3 g of compound 4 were added to the reaction flask, 675 mL of DCM was added, stirring was started, 133.8 g of DBU was added dropwise under temperature control at 5 to 15 °C, the reaction was performed for 2 h, and HPLC monitored the complete conversion of raw materials, and 804 mL of water was added. The reaction was quenched, acetic acid was added dropwise to adjust the pH to 6-7, and after stirring for 10 min, the solution was separated, and the aqueous phase was extracted with 402 mL of DCM, which was repeated twice. The combined organic phases were concentrated to 1 vol under reduced pressure at 35°C, a white solid was precipitated, 536 mL of MTBE was added to make a slurry for 1 h, suction filtered, and the filter cake was rinsed with 134 mL of MTBE to obtain 199.2 g of off-white solid compound 5, yield 94.6%, purity 96.0%.

Reference： [1]Current Patent Assignee: SUZHOU PENGXU PHARMATECH CO., LTD.; NANJING F S PHARMATECH - WO2021/252295, 2021, A1 Location in patent: Paragraph 0036
[2]Current Patent Assignee: SUZHOU PENGXU PHARMATECH CO LTD - CN114436878, 2022, A Location in patent: Paragraph 0023-0025

85
[ 67-36-7 ]
[ 1227060-32-3 ]
C₁₉H₁₉NO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90.4%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 0 - 20℃; for 1h;	7 Example 7: Synthesis of compound 7 To a round-bottom flask were added compound 1 (45.0 g), compound 4 (60.4 g) and DCM (225 mL). DBU (44.4 g) was added dropwise at 0~10 °C. The reaction mixture was warmed to room temperature and stirred for 1 h. The reaction mixture was quenched with ThO (225 mL). The layers were separated. The organic phase was concentrated to dryness. The crude product was added MTBE (180 mL) and stirred at room temperature for 1 h. The suspension was filtered to give compound 5 as a white solid (566.8 g, 90.4% yield, 100% purity). NMR (400 MHz, CDCh) d 7.48 - 7.37 (m, 4H), 7.20 - 7.13 (m, 2H), 7.09 - 7.06 (m, 2H), 6.98 - 6.96 (m, 2H), 4.31 (q, J= 7.1 Hz, 2H), 2.16 (s, 3H), 1.37 (t, J= 7.1 Hz, 3H).Mass: [M+H]+: 326.3
90.4%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 0 - 20℃; for 1h;	3 Synthesis of 2-Acetylamino-3-(4-phenoxyphenyl)propionic acid ethyl ester (8) 225 mL of DCM, 45 g of compound 3 and 60.4 g of compound 4 were sequentially added to the reaction flask, cooled to 0-10°C, 44.4 g of DBU was added dropwise, and the reaction was slowly raised to room temperature for 1 h. HPLC monitored the end of the reaction, and added 225 The reaction was quenched with mL water, separated, and the organic phase was concentrated to dryness to obtain the crude product, which was added to 180 mL of MTBE, beaten at room temperature for 1 h, filtered, and rinsed with 90 mL of MTBE to obtain 566.8 g of white solid product 7, yield 90.4%, purity 100%.

Reference： [1]Current Patent Assignee: SUZHOU PENGXU PHARMATECH CO., LTD.; NANJING F S PHARMATECH - WO2021/252295, 2021, A1 Location in patent: Paragraph 0043
[2]Current Patent Assignee: SUZHOU PENGXU PHARMATECH CO LTD - CN114436878, 2022, A Location in patent: Paragraph 0029-0031

86
[ 67-36-7 ]
(3S,4r,5R)-piperidine-3,4,5-triyl triacetate [ No CAS ]
(3S,4r,5R)-1-(4-phenoxybenzyl)piperidine-3,4,5-triyl triacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With sodium tris(acetoxy)borohydride In dichloromethane at 20℃; for 18h;	201 [00299] To a stirred solution of (3S,4r,5R)-piperidine-3,4,5-triyl triacetate (0.100 g, 0.386 mmol) and 4-phenoxybenzaldehyde (0.110 g, 0.557 mmol) in DCM (10 mL) was added NaBH(OAc)3 (0.15 mg, 0.71 mmol), and the mixture was stirred at RT for 18 h. The mixture was diluted with satd. aqueous NaHCO3 (10 mL) and extracted with DCM (2 × 10 mL). The combined extract was dried over anhydrous Na2SO4. After filtration the solvent was evaporated under reduced pressure, and the residue was purified on silica gel by flash chromatography (EtOAc/hexanes, 1:6 to 1:4), affording (3S,4r,5R)-1-(4-phenoxybenzyl)piperidine-3,4,5-triyl triacetate as a white solid (0.14 g, 82%). ESI MS m/z 442.19 [M + H]+.
82%	With sodium tris(acetoxy)borohydride In dichloromethane at 20℃; for 18h;	201 [00299] To a stirred solution of (3S,4r,5R)-piperidine-3,4,5-triyl triacetate (0.100 g, 0.386 mmol) and 4-phenoxybenzaldehyde (0.110 g, 0.557 mmol) in DCM (10 mL) was added NaBH(OAc)3 (0.15 mg, 0.71 mmol), and the mixture was stirred at RT for 18 h. The mixture was diluted with satd. aqueous NaHCO3 (10 mL) and extracted with DCM (2 × 10 mL). The combined extract was dried over anhydrous Na2SO4. After filtration the solvent was evaporated under reduced pressure, and the residue was purified on silica gel by flash chromatography (EtOAc/hexanes, 1:6 to 1:4), affording (3S,4r,5R)-1-(4-phenoxybenzyl)piperidine-3,4,5-triyl triacetate as a white solid (0.14 g, 82%). ESI MS m/z 442.19 [M + H]+.
82%	With sodium tris(acetoxy)borohydride In dichloromethane at 20℃; for 18h;	201 [00299] To a stirred solution of (3S,4r,5R)-piperidine-3,4,5-triyl triacetate (0.100 g, 0.386 mmol) and 4-phenoxybenzaldehyde (0.110 g, 0.557 mmol) in DCM (10 mL) was added NaBH(OAc)3 (0.15 mg, 0.71 mmol), and the mixture was stirred at RT for 18 h. The mixture was diluted with satd. aqueous NaHCO3 (10 mL) and extracted with DCM (2 × 10 mL). The combined extract was dried over anhydrous Na2SO4. After filtration the solvent was evaporated under reduced pressure, and the residue was purified on silica gel by flash chromatography (EtOAc/hexanes, 1:6 to 1:4), affording (3S,4r,5R)-1-(4-phenoxybenzyl)piperidine-3,4,5-triyl triacetate as a white solid (0.14 g, 82%). ESI MS m/z 442.19 [M + H]+.

Reference： [1]Current Patent Assignee: ALECTOS THERAPEUTICS INC - WO2021/224864, 2021, A1 Location in patent: Paragraph 00299
[2]Current Patent Assignee: ALECTOS THERAPEUTICS INC - WO2021/224864, 2021, A1 Location in patent: Paragraph 00299
[3]Current Patent Assignee: ALECTOS THERAPEUTICS INC - WO2021/224864, 2021, A1 Location in patent: Paragraph 00299

87
[ 67-36-7 ]
[ 36692-49-6 ]
methyl 2-(4-phenoxyphenyl)-1H-benzimidazole-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	Stage #1: 4-phenoxy benzaldehyde With sodium metabisulfite In ethanol; water at 20℃; Stage #2: Methyl 3,4-diaminobenzoate In N,N-dimethyl-formamide at 60℃; for 4h;	Methyl 2-(4-(benzyloxy)phenyl)-1H-benzimidazole-5-carboxylate (7) General procedure: To a solution of 4-(benzyloxy)benzaldehyde (1 eq) in EtOH (3 mL), sodium metabisulfite (1.5 eq) solution in water (1 mL) was added dropwise. The resulting mixture was stirred at rt overnight. After completion, the mixture was diluted with EtOH and ice-cooled. The precipitated product was filtered. In a solution of benzaldehyde bisulfite adduct (1.1 eq) in 4 mL DMF, methyl 3,4-diaminobenzoate (1 eq) was added, and the resulting mixture was heated at 60 C for 4 h. After completion, the mixture was poured into distilled water, and the precipitated product was filtered off, and used without further purification in next step (89% yield).
84%	Stage #1: 4-phenoxy benzaldehyde With sodium metabisulfite In ethanol; water at 20℃; Stage #2: Methyl 3,4-diaminobenzoate In N,N-dimethyl-formamide at 60℃; for 4h;	Methyl 2-(4-(benzyloxy)phenyl)-1H-benzimidazole-5-carboxylate (7) General procedure: To a solution of 4-(benzyloxy)benzaldehyde (1 eq) in EtOH (3 mL), sodium metabisulfite (1.5 eq) solution in water (1 mL) was added dropwise. The resulting mixture was stirred at rt overnight. After completion, the mixture was diluted with EtOH and ice-cooled. The precipitated product was filtered. In a solution of benzaldehyde bisulfite adduct (1.1 eq) in 4 mL DMF, methyl 3,4-diaminobenzoate (1 eq) was added, and the resulting mixture was heated at 60 C for 4 h. After completion, the mixture was poured into distilled water, and the precipitated product was filtered off, and used without further purification in next step (89% yield).

Reference： [1]Banoglu, Erden; Jordan, Paul M.; Kretzer, Christian; Werz, Oliver; Çalışkan, Burcu; Ergül, Azize Gizem; Maz, Tuğçe Gür; Olğaç, Abdurrahman [European Journal of Medicinal Chemistry, 2022, vol. 231]
[2]Banoglu, Erden; Jordan, Paul M.; Kretzer, Christian; Werz, Oliver; Çalışkan, Burcu; Ergül, Azize Gizem; Maz, Tuğçe Gür; Olğaç, Abdurrahman [European Journal of Medicinal Chemistry, 2022, vol. 231]

88
[ 67-36-7 ]
C₅H₅N₅*2ClH [ No CAS ]
[ 330786-24-8 ]

Yield	Reaction Conditions	Operation in experiment
96.8%	Stage #1: 4-phenyloxybenzaldehyde With sodium hydrogen sulphite In ethanol; water monomer at 20℃; Stage #2: C₅H₅N₅*2ClH In N,N-dimethyl-formamide Reflux; Stage #3: With hydrogenchloride; sodium tetrahydridoborate; nickel (II) chloride In N,N-dimethyl-formamide at 20℃;	14-27 Example 14 Compound VII (99.11 g, 0.5 mol) was dissolved in ethanol (500 mL) at room temperature, and an aqueous solution of sodium bisulfite (600 mL, 1.0 mol/L) was slowly added, stir the reaction, separate the precipitate in the reaction solution, add it to 500 mL of DMF after drying, add VI (102.95 g, 0.6 mol) and reflux for 4 to 5 hours, after the reaction solution was cooled to room temperature, nickel dichloride (71.28g, 0.55mol), sodium borohydride (75.66g, 2.0mol) were added, and 60mL of 5N hydrochloric acid continued to stir at room temperature until the reaction finished, after the reaction, the reaction mixture was filtered, and the filtrate was washed to neutrality, and then dichloromethane (300 mL) was added for extraction. The organic layer was poured into 300 mL of ice water, the precipitate was collected, and crystallized with ethanol (200 mL) to obtain compound VIII with a yield of 96.8% and a HPLC purity of 99.89%.

Reference： [1]Current Patent Assignee: LUNAN PHARMACEUTICAL GROUP CO LTD - CN113929686, 2022, A Location in patent: Paragraph 0030; 0112-0140

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

CAS No. :	67-36-7	MDL No. :	MFCD00003383
Formula :	C₁₃H₁₀O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	QWLHJVDRPZNVBS-UHFFFAOYSA-N
M.W :	198.22	Pubchem ID :	66139
Synonyms :

Num. heavy atoms :	15
Num. arom. heavy atoms :	12
Fraction Csp3 :	0.0
Num. rotatable bonds :	3
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	58.35
TPSA :	26.3 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	Yes
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.33 cm/s

Log Po/w (iLOGP) :	2.28
Log Po/w (XLOGP3) :	3.07
Log Po/w (WLOGP) :	3.29
Log Po/w (MLOGP) :	2.61
Log Po/w (SILICOS-IT) :	3.22
Consensus Log Po/w :	2.89

[ CAS No. 67-36-7 ] {[proInfo.proName]}

Quality Control of [ 67-36-7 ]

Related Doc. of [ 67-36-7 ]

Product Details of [ 67-36-7 ]

Calculated chemistry of [ 67-36-7 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 67-36-7 ]

Application In Synthesis of [ 67-36-7 ]

[ 67-36-7 ] Synthesis Path-Upstream 1~4

[ 67-36-7 ] Synthesis Path-Downstream 1~88

Related Functional Groups of
[ 67-36-7 ]

Aryls

Aldehydes

Ethers

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Log S (ESOL) :	-3.4
Solubility :	0.0795 mg/ml ; 0.000401 mol/l
Class :	Soluble
Log S (Ali) :	-3.29
Solubility :	0.102 mg/ml ; 0.000514 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.61
Solubility :	0.00489 mg/ml ; 0.0000247 mol/l
Class :	Moderately soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.36

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

Yield	Reaction Conditions	Operation in experiment
75%	With hydroxylamine hydrochloride In ethanol; water at 20℃; Inert atmosphere	A solution of 4-phenoxybenzaldehyde (2.0 g, 10 mmol), hydroxylamine hydrochloride (700 mg, 10 mmol), EtOH (20 ml), and water (1 ml) was stirred at room temperature overnight. To the reaction mixture were added 10 N Hci (1 ml) and of Pd/C (10percent on carbon, 320 mg) and was stirred under hydrogen for 30 min. The reaction mixture was filtrated through Celite and concentrated to dryness. The residue was purified by flash column chromatography to give the title compound as a white solid (1.5 g, 75percent yield).
75%	Stage #1: With hydroxylamine hydrochloride In ethanol; water at 20℃; Stage #2: With hydrogenchloride; palladium 10% on activated carbon; hydrogen In ethanol; water for 0.5 h;	A solution of 4-phenoxybenzaldehyde (2.0 g, 10 mmol), hydroxylamine hydrochloride (700 mg, 10 mmol), EtOH (20 ml), and water (1 ml) was stirred at room temperature overnight. To the reaction mixture were added 10 N HCl (1 ml) and of Pd/C (10percenton carbon, 320 mg) and was stirred under hydrogen for 30 min. The reaction mixture was filtrated through Celite and concentrated to dryness. The residue was purified by flash column chromatography to give the title compound as a white solid (1.5 g, 75percent yield).

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.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
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

[ CAS No. 67-36-7 ] {[proInfo.proName]}

Quality Control of [ 67-36-7 ]

Related Doc. of [ 67-36-7 ]

Product Details of [ 67-36-7 ]

Calculated chemistry of [ 67-36-7 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 67-36-7 ]

Application In Synthesis of [ 67-36-7 ]

[ 67-36-7 ] Synthesis Path-Upstream 1~4

[ 67-36-7 ] Synthesis Path-Downstream 1~88

Related Functional Groups of [ 67-36-7 ]

Aryls

Aldehydes

Ethers

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 67-36-7 ]