Name: 23981-80-8|2-(6-Methoxynaphthalen-2-yl)propanoic acid|98%
Brand: Ambeed
SKU: A152209
Price: 13.0 USD
Availability: InStock
Rating: 90 (29 reviews)

1
[ 908094-01-9 ]
[ 23981-80-8 ]
[ 30012-51-2 ]

Yield	Reaction Conditions	Operation in experiment
65%	In diethyl ether at 0℃; for 1h;

Reference： [1]Hiyama; Inoue [Synthesis, 1986, vol. NO. 8, # 8, p. 689 - 691]

2
[ 122-96-3 ]
[ 23981-80-8 ]
N,N'-di<α-(6-metossi-2-naftil)propionilossi-2-etil>piperazina [ No CAS ]

Reference： [1]Farmaco, Edizione Scientifica,1985,vol. 40,p. 334 - 346

3
[ 67-56-1 ]
[ 23981-80-8 ]
[ 30012-51-2 ]

Yield	Reaction Conditions	Operation in experiment
100%	With sulfuric acid
100%		2 Example 2; Methyl (RS)-2-(6-methoxynaphthalen-2-yl)propanoate; To a solution of (fiS)-2-(6-methoxynaphthalen-2-yl)piOpanoic acid (14.25 g, 62.8 mmol) in methanol (450 ml_) was added 70 drops of concentrated H2SO4 and the reaction mixture was stirred for overnight before it was diluted with CH2CI2 (approx. 1 L), washed with aqueous saturated NaHCO3 and dried over Na2SO4. Solvent evaporation gave the title methyl ester quantitatively. 1H NMR (400 MHz, CDCI3): δ = 7.62 (s, 1 H), 7.57 (d, 1 H, J = 8.5 Hz), 7.48-7.45 (m, 2H), 7.18 (d, 1 H, J = 2.6 Hz), 6.89 (d, 1 H, J = 2.4 Hz), 3.71 (q, 1 H, J = 7.1 Hz), 3.36 (s, 3H), 3.28 (s, 3H), 1.52 (d, 3H, J = 7.1 Hz).
100%	With sulfuric acid for 6h; Reflux;	3.1 In a 250 mL flask connected to a reflux condenser there were added 0.7 g (3 mmol) of naproxen, 50 mL of methanol and 2 drops of concentrated sulfuric acid. The reaction is kept under reflux and stirring for 6 hours until thin layer chromatography indicated the completion of the reaction (Mobile phase: 90% dichloromethane; 10% methanol).The product was obtained by removing the solvent at reduced pressure to provide 0.74 g of an orange color solid with melting range between 88°-94° C. (C15H16O3, MW=244.11, yield: 100%).The NMR H1 spectrum (400 MHz, DMSOd) was as follows: δ 1.47 (d; 3H); 3.59 (s; 3H); 3.86 (s; 3H); 3.94 (q; 1H); 7.15 (dd; 1H; Jorto=8.7 Hz and Jmeta=2.56 Hz); 7.29 (d; 1H; Jmeta=2.56 Hz); 7.38 (dd; 1H; Jorto=8.53 Hz and Jmeta=1.87 Hz); 7.72 (d; 1H); 7.79 (Jorto=8.87 Hz; 2H) ppm.The IR spectrum (KBr pellet) was as follows: ν 2976 (C-H, CH2 and CH3) ν 1739.7 (COester) δ 1604, 1450 (C-Haromatic); V 1267 (C-O) cm-1.

98%	Stage #1: methanol; 2-(6-methoxy-naphthalen-2-yl)-propionic acid With dmap In dichloromethane at 0℃; for 0.0833333h; Stage #2: With dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃; for 3.08333h;
96%	With sulfuric acid In chloroform at 70℃; for 3h; Dean-Stark;
96%	With sulfuric acid; magnesium(II) sulfate In dichloromethane at 20℃; for 24h;
95%	With sulfuric acid at 20℃; for 2h;
92%	With sulfuric acid at 60 - 70℃; for 1.16667h;
73%	With thionyl chloride for 2h; Heating;
	With sulfuric acid for 6h; Heating;
	With thionyl chloride at 0 - 20℃;
	With sulfuric acid Heating;
	With sulfuric acid for 6h; Reflux;
	With sulfuric acid at 55℃; for 18h;
	With sulfuric acid for 2h; Reflux;
	With sulfuric acid for 3h; Reflux;
	With sulfuryl dichloride Reflux;
	With sulfuric acid for 14h; Reflux;
17.2 mg	With diazomethyl-trimethyl-silane In toluene at 20℃; for 1h;

Reference： [1]Noorduin, Wim L.; Kaptein, Bernard; Meekes, Hugo; Enckevort, Willem J. P. van; Kellogg, Richard M.; Vlieg, Elias [Angewandte Chemie - International Edition, 2009, vol. 48, p. 4581 - 4583][Angew. Chem., Int. Ed., 2009, vol. 121, p. 4651 - 4653]
[2]Current Patent Assignee: KONINKLIJKE DSM N.V. - WO2010/89343, 2010, A1 Location in patent: Page/Page column 8-9
[3]Current Patent Assignee: UNIVERSIDAE ESTADUAL PAULISTA - US2012/115817, 2012, A1 Location in patent: Page/Page column 43
[4]Liang, Yu-Feng; Jiao, Ning [Angewandte Chemie - International Edition, 2014, vol. 53, # 2, p. 548 - 552][Angew. Chem., 2014, vol. 53, # 2, p. 558 - 562,5]
[5]Gilani, Saeedeh L.; Najafpour, Ghasem D.; Heydarzadeh, Hamid D.; Moghadamnia, Aliakbar [Chirality, 2017, vol. 29, # 6, p. 304 - 314]
[6]Xie, Qiqiang; Zhu, Ziyue; Li, Lingchun; Ni, Chuanfa; Hu, Jinbo [Angewandte Chemie - International Edition, 2019, vol. 58, # 19, p. 6405 - 6410][Angew. Chem., 2019, vol. 131, # 19, p. 6471 - 6476,6]
[7]Muñoz-Muñiz, Omar; Juaristi, Eusebio [Tetrahedron Letters, 2003, vol. 44, # 10, p. 2023 - 2026]
[8]Koul, Surrinder; Parshad, Rajinder; Taneja, Subhash C.; Qazi, Ghulam N. [Tetrahedron Asymmetry, 2003, vol. 14, # 16, p. 2459 - 2465]
[9]Giorno; D'Amore; Drioli; Cassano; Picci [Journal of Catalysis, 2007, vol. 247, # 2, p. 194 - 200]
[10]Ghislandi; La Manna; Azzolina; et al. [Farmaco, Edizione Scientifica, 1982, vol. 37, # 2, p. 81 - 93]
[11]Fujisawa, Hidehito; Fujiwara, Tomoya; Takeuchi, Yoshio; Omata, Kenji [Chemical and Pharmaceutical Bulletin, 2005, vol. 53, # 5, p. 524 - 528]
[12]Stock, Nicholas; Munoz, Benito; Wrigley, Jonathan D.J.; Shearman, Mark S.; Beher, Dirk; Peachey, James; Williamson, Toni L.; Bain, Gretchen; Chen, Weichao; Jiang, Xiaohui; St-Jacques, Rene; Prasit, Peppi [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 8, p. 2219 - 2223]
[13]Location in patent: experimental part Parcha, Versha; Kaur, Jaswinder; Gupta, Vinay; Anroop [Journal of the Indian Chemical Society, 2008, vol. 85, # 3, p. 321 - 325]
[14]Wang, Pei-Yun; Chen, Ying-Ju; Wu, An-Chi; Lin, Yi-Sheng; Kao, Min-Fang; Chen, Jin-Ru; Ciou, Jyun-Fen; Tsai, Shau-Wei [Advanced Synthesis and Catalysis, 2009, vol. 351, # 14-15, p. 2333 - 2341]
[15]Windsor, Matthew A.; Hermanson, Daniel J.; Kingsley, Philip J.; Xu, Shu; Crews, Brenda C.; Ho, Winnie; Keenan, Catherine M.; Banerjee, Surajit; Sharkey, Keith A.; Marnett, Lawrence J. [ACS Medicinal Chemistry Letters, 2012, vol. 3, # 9, p. 759 - 763]
[16]Aydin, Sevil; Kaushik-Basu, Neerja; Oezbas-Turan, Suna; Akbuga, Juelide; Tiber, Pinar Mega; Orun, Oya; Gurukumar; Basu, Amartya; Kuecuekguezel, S. Gueniz [Letters in drug design and discovery, 2014, vol. 11, # 2, p. 121 - 131]
[17]Li, Zhiyou; Wu, Lamei; Zhang, Tao; Huang, Zhengxi; Qiu, Guofu; Zhou, Zhongqiang; Jin, Longfei [Dalton Transactions, 2014, vol. 43, # 20, p. 7554 - 7560]
[18]Abrams, M. Leigh; Buser, Jonas Y.; Calvin, Joel R.; Johnson, Martin D.; Jones, Bradley R.; Lambertus, Gordon; Landis, Clark R.; Martinelli, Joseph R.; May, Scott A.; McFarland, Adam D.; Stout, James R. [Organic Process Research and Development, 2016, vol. 20, # 5, p. 901 - 910]
[19]Jiang, Yi-Qian; Lan, Yu; Li, Shi-Jun; Li, Wen-Duo; Li, Yan-Lin; Wu, Yang; Xia, Ji-Bao [Journal of the American Chemical Society, 2021]

4
[ 64-17-5 ]
[ 23981-80-8 ]
[ 31220-35-6 ]

Yield	Reaction Conditions	Operation in experiment
80%		A solution of commercially available racemic <strong>[23981-80-8]naproxen</strong> (0.92g, 4.0 mmol) in thionyl chloride (5mL) was refluxed until the evolution of the HCl gas had ceased (ca. 4 h). The excess thionyl chloride was removed in vacuo and a 1 : 1 mixture of ethanol (3mL) : dichloromethane (3mL) was added with refluxing for further 2h. The solution was cooled and the solvent removed in vacuo to give <strong>[23981-80-8]naproxen</strong> ethyl ester as a colourless oil (1.03g, 80%) after purification via flash chromatography (96 : 4) ) (hexane: ethyl acetate).
	With sulfuric acid; at 65℃;	General procedure: The reactant (2.5 g of racemic ibuprofen, <strong>[23981-80-8]naproxen</strong> or ketoprofen)was mixed with EtOH (100 mL) ethanol and sulfuric acid(1 mL). The mixture was stirred at 65 C overnight. Then calcium carbonate (2.5 g) was then added and the mixture was stirred again for 30 min. The precipitate was removed by filtration and the filtrate was dried under reduced pressure. The reaction was followedby Thin Layer Chromatography analysis (TLC) using hexane/isopropanol (99/1 v/v) as the eluent. 1H NMR spectra were recorded on a Bruker AC-200.1 (200.1 MHz) spectrometer and confirmedthe purity of both esters.

Reference： [1]Angewandte Chemie - International Edition,2009,vol. 48,p. 4581 - 4583
Angew. Chem., Int. Ed.,2009,vol. 121,p. 4651 - 4653
[2]Patent: WO2004/11473,2004,A1 .Location in patent: Page/Page column 27-28
[3]Tetrahedron,1994,vol. 50,p. 10749 - 10760
[4]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1999,vol. 38,p. 237 - 239
[5]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 4504 - 4508
[6]Archiv der Pharmazie,2007,vol. 340,p. 577 - 585
[7]Organic and Biomolecular Chemistry,2010,vol. 8,p. 4117 - 4123
[8]Medicinal Chemistry Research,2014,vol. 23,p. 827 - 838
[9]Medicinal Chemistry,2015,vol. 11,p. 753 - 763
[10]Tetrahedron Asymmetry,2017,vol. 28,p. 433 - 441

5
[ 201230-82-2 ]
[ 72775-41-8 ]
[ 23981-80-8 ]

Yield	Reaction Conditions	Operation in experiment
99%	With water; toluene-4-sulfonic acid; triphenylphosphine; lithium chloride;1% Rh/C; In butanone; at 115℃; under 41372.9 Torr;	[01194] A 50 ml stirred autoclave was charged with the following reactants [01195] 1-(6-methoxy-2-naphthyl)ethyl chloride: 2.5 g [01196] 1% Rh/C: 0.1 g [01197] triphenyl phosphine: 0.08165 g [01198] p-toluene sulphonic acid: 1.065 g [01199] LiCl: 0.2365 g [01200] H2O: 1.2 ml [01201] Methyl ethyl ketone: 21.5 ml [01202] The contents of the autoclave were flushed with nitrogen and then many times with carbon monoxide. Thereafter, the contents were heated to 115 C. After the temperature is attained, the autoclave was pressurised to 800 psig with carbon monoxide, stirring started and it was observed that gas absorption commenced immediately. For synthesis of naproxen, the pressure in the autoclave was maintained constant using carbon monoxide and the progress of the reaction was monitored by observing the pressure drop and by liquid sampling. The reaction was continued until the pressure drop was too low. The reactor was then cooled and the liquid phase analyzed by gas chromatography. [01203] The GC analysis showed TOF of 150 h-1 and 98% conversion of 1-(6-methoxy-2-naphthyl)ethyl chloride with naproxen selectivity of 99%. The catalyst was filtered out and the solvent evaporated and the reaction mixture re-dissolved in toluene. The precipitated solid portion, which is a mixture of LiCl and lithium salt of p-toluene sulphonic acid was filtered out. The filtrate was treated with saturated solution of sodium bicarbonate two-three times and the aqueous phase separated to obtain the sodium salt of naproxen, which on hydrolysis with acid and extraction with dichloromethane, evaporation and vacuum distillation gives the pure product.
99%	With water; toluene-4-sulfonic acid; triphenylphosphine; lithium chloride;1% Pd/C; In butanone; at 115℃; under 41372.9 Torr;	[00821] A 50 ml stirred autoclave was charged with the following reactants [00822] 1-(6-methoxy-2-naphthyl)ethyl chloride: 1 g [00823] 1% Ru/C: 0.1 g [00824] triphenyl phosphine: 0.08165 g [00825] p-toluene sulphonic acid: 0.5 g [00826] LiCl: 0.1 g [00827] H2O: 1.2 ml [00828] Methyl ethyl ketone: 21.5 ml [00829] The contents of the autoclave were flushed with nitrogen and then many times with carbon monoxide. Thereafter, the contents were heated to 115 C. After the temperature is attained, the autoclave was pressurised to 800 psig with carbon monoxide, stirring started and it was observed that gas absorption commenced immediately. For synthesis of naproxen, the pressure in the autoclave was maintained constant using carbon monoxide and the progress of the reaction was monitored by observing the pressure drop and by liquid sampling. The reaction was continued until the pressure drop was too low. The reactor was then cooled and the liquid phase analyzed by gas chromatography. [00830] The GC analysis showed TOF of 120 h-1 and 99% conversion of 1-(6-methoxy-2-naphthyl)ethyl chloride with naproxen selectivity of 99%. The catalyst was filtered out and the solvent evaporated and the reaction mixture re-dissolved in toluene. The precipitated solid portion, which is a mixture of LiCl and lithium salt of p-toluene sulphonic acid was filtered out. The filtrate was treated with saturated solution of sodium bicarbonate two-three times and the aqueous phase separated, which on hydrolysis and extraction with dichloromethane gives the pure product.
98%	With toluene-4-sulfonic acid; triphenylphosphine; lithium chloride;1% Pd/ZSM 5; In water; butanone; at 115℃; under 41372.9 Torr;	EXAMPLE 42 [00214] A 50 ml stirred autoclave was charged with the following reactants [00215] 1-(6-methoxy-2-naphthyl)ethyl chloride: 1 g [00216] 1% Pd/C: 0.1 g [00217] triphenyl phosphine: 0.08165 g [00218] p-toluene sulphonic acid: 0.51 g [00219] LiCl: 0.1 g [00220] H2O: 1.2 ml [00221] Methyl ethyl ketone: 21.5 ml. [00222] The contents of the autoclave were flushed with nitrogen and then many times with carbon monoxide. Thereafter, the contents were heated to 115 C. After the temperature is attained, the autoclave was pressurised to 800 psig with carbon monoxide, stirring started and it was observed that gas absorption commenced immediately. For synthesis of naproxen the pressure in the autoclave was maintained constant using carbon monoxide and the progress of the reaction was monitored by observing the pressure drop and by liquid sampling. The reaction was continued until the pressure drop was too low. The reactor was then cooled and the liquid phase analyzed by gas chromatography. [00223] The GC analysis showed TOF of 130 h-1 and 98% conversion of 6-methoxy naphthyl ethanol with naproxen selectivity of 98%. The catalyst was filtered out and the solvent evaporated and the reaction mixture re-dissolved in toluene. The precipitated solid portion, which is a mixture of LiCl and lithium salt of p-toluene sulphonic acid was filtered out. The filtrate is treated with saturated solution of sodium bicarbonate two-three times and the aqueous phase is separated which on hydrolysis and extraction with dichloromethane gives the pure product.

With toluene-4-sulfonic acid; lithium chloride;bis-triphenylphosphine-palladium(II) chloride; In water; butanone; at 115℃; under 42133.0 Torr;Product distribution / selectivity;

A 50 ml stirred autoclave was charged with the following reactants 1-(6'-methoxy-2-naphthyl) ethyl chloride: 0.02808 mol PdCl2(PPh3)2: 5.6×10-5 mol p-toluene sulphonic acid: 0.0056 LiCl: 0.0056 mol H2O: 1.25 mL Methyl ethyl ketone: 19 mL The contents of the autoclave were flushed with nitrogen and then many times with carbon monoxide. Thereafter, the contents were heated to 115 C. After the temperature is attained, the autoclave was pressurized to 800 psig with carbon monoxide, stirring started and it was observed that gas absorption commenced immediately. For synthesis of naproxen, the pressure in the autoclave was maintained constant using carbon monoxide and the progress of the reaction was monitored by observing the pressure drop and by liquid sampling. The reaction was continued until the pressure drop was too low. The reactor was then cooled and the final reaction mixture analyzed by gas chromatography. The GC analysis showed TOF of 425 h-1 and 99% conversion of 1-(6'-methoxy-2-naphthyl) ethyl chloride with naproxen selectivity of 97.5% and n/iso ratio of 0.025. The solvent was evaporated and the reaction mixture was re-dissolved in toluene. The solid portion, which is a mixture of LiCl and lithium salt of p-toluene sulphonic acid was filtered out. The filtrate was treated with saturated solution of sodium bicarbonate two to three times and the aqueous phase was separated which on hydrolysis with acid and extraction with dichloromethane, evaporation gave pure naproxen product.

Reference： [1]Patent: US6660883,2003,B1 .Location in patent: Page column 70
[2]Patent: US6660883,2003,B1 .Location in patent: Page column 50
[3]Patent: US6660883,2003,B1 .Location in patent: Page column 16-17
[4]Journal of Organometallic Chemistry,1985,vol. 282,p. 277 - 282
[5]Journal of Organometallic Chemistry,1982,vol. 232,p. 59 - 70
[6]Patent: US2005/283020,2005,A1 .Location in patent: Page/Page column 4

6
[ 27602-75-1 ]
[ 23981-80-8 ]

Reference： [1]Organic Letters,2019,vol. 21,p. 1393 - 1396
[2]Chemistry Letters,1984,p. 341 - 344
[3]Tetrahedron Letters,1986,vol. 27,p. 3995 - 3998
[4]Chemical Communications,2009,p. 5299 - 5301

7
[ 23981-80-8 ]
[ 52079-10-4 ]

Yield	Reaction Conditions	Operation in experiment
96%		A mixture of <strong>[23981-80-8]naproxen</strong> (1.15 g, 5.00 mmol) in glacial acetic acid (10 mL) was treated with 48% aqueous HBr (2.5 mL) and heated to 150 C. for three hours. A majority of the solvent and acid was distilled off and the mixture was cooled to ambient temperature. The resulting solid was treated with H2O (20 mL), stirred 30 minutes, filtered, washed with H2O and hexane, and dried under reduced pressure to afford an off-white solid (1.038 g, 4.80 mmol, 96%). 1H NMR (300 MHz, acetone-d6) 1.63 (d, 3H), 3.62 (s, 3H), 3.90 (q, 2H), 7.18 (m, 2H), 7.41 (m, 1H), 7.67 (m, 1H), 7.78 (m, 2H).
75%	With hydrogen bromide; acetic acid; for 4h;Reflux;	Synthesis of Compound 2: To the solution of Naproxen (Compound 1, 5 g, 23 mmol) in AcOH (50 mL) was added HBr (47%, 25 mL). After the mixture was refluxed for 4 hours, the whole reaction mixture was condensed under reduced pressure then washed with water. The precipitate thus obtained was filtered, washed with petroleum ether, and recrystallized from toluene to give (7-hydroxynaphthalen-l- yl) acetic acid (Compound 2, 3.52 g, 75%). XH NMR (CDC13,500 MHz): 7.64 (d, J= 8.8 Hz, 2H), 7.62 (s, 1H), 7.58 (d, J = 8.3 Hz, 2H), 7.35 (dd, J= 8.8, 1.46 Hz, 1H), 7.09 (s, 1H), 7.08 (dd, J= 8.8, 1.45 Etazeta, IotaEta), 3.77 (q, J= 7.3 Hz, 1H), 1.52 (d, J= 7.3 Hz, 3H). ESI-MS: m/z 217 (M++l).

Reference： [1]Patent: US2007/276042,2007,A1 .Location in patent: Page/Page column 58
[2]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 3426 - 3436
[3]Patent: WO2013/25790,2013,A2 .Location in patent: Page/Page column 92; 93
[4]Journal of medicinal chemistry,1970,vol. 13,p. 203 - 205
[5]Journal of Medicinal Chemistry,1992,vol. 35,p. 1246 - 1259
[6]Biochemical Pharmacology,2011,vol. 82,p. 789 - 796

8
[ 23981-80-8 ]
[ 38835-18-6 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; In chloroform;	c) 7 ml of thionyl chloride were cautiously added to a solution of 2.3 g of 2-(6-methoxy-2-naphtyl)propionic acid in 15 ml of anhydrous chloroform. The reaction mixture was stirred for 40 minutes at room temperature and then the solvent was evaporated at a reduced pressure, obtaining 2.23 g of 2-(6-methoxy-2-naphtyl)propionylchloride.
	With thionyl chloride; for 4h;Heating / reflux;	A solution of commercially available racemic <strong>[23981-80-8]naproxen</strong> (0.92g, 4.0 mmol) in thionyl chloride [(5ML)] was refluxed until the evolution of the [HCL] gas had ceased (ca. 4 h). The excess thionyl chloride was removed in vacuo and a 1: 1 mixture of ethanol (3mL): [DICHLOROMETHANE] (3mL) was added with refluxing for further 2h. The solution was cooled and the solvent removed in vacuo to give <strong>[23981-80-8]naproxen</strong> ethyl ester as a colourless oil (1.03g, 80%) after purification via flash chromatography (96: 4) ) (hexane: ethyl acetate).
	With thionyl chloride; In benzene;Reflux;	General procedure: A solution of NSAIDs having carboxylic acid group (1a-h) (1 mmol) in dry benzene (5-8 mL) was refluxed with freshly distilled thionyl chloride (1.2 mmol) for 2-3 h. After the completion of reaction, excess of thionyl chloride was removed under reduce pressure to afford the acid chlorides (2a-h) which were dissolved in anhydrous acetone for further use. The acid chlorides (2a-h) were then treated with a solution of (+)-6-aminopenicillanic acid (6-APA, 1 mmol) in 2% NaHCO3 (40 mL) diluted with acetone (30 mL). The reaction mixture was stirred for 2-4 h at room temperature and then concentrated under reduced pressure and washed with ethyl acetate (25 mL). The aqueous layer was then acidified with HCl (0.1 M), extracted with ethyl acetate and then washed with distilled water dried over anhydrous Na2SO4. The ethyl acetate was rotary evaporated and triturated with n-hexane to afford the title compounds (4a-h).

With thionyl chloride; In N,N-dimethyl-formamide; at 25 - 75℃;Inert atmosphere;

General procedure: A solution of the carboxylic acid drug (3) (0.031 mol) and DMF in dry SOCl2 (3-10 mL) was heated at 25-75 C for 2-5 h under a nitrogen atmosphere. Then the reaction mixture was concentrated by evaporation. The residue was added to a solution of (2) (0.012 mol) in 40 mL acetonitrile and stirred for 2-4 h at room temperature, while monitoring the reaction by TLC. Finally, the reaction product was concentrated in vacuo and purified by silica gel with CH2Cl2/CH3OH (70:1-10:1) as eluent to obtain the proposed compound.

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 4609 - 4611
[2]Russian Chemical Bulletin,2011,vol. 60,p. 948 - 954
[3]Journal of Medicinal Chemistry,1992,vol. 35,p. 1246 - 1259
[4]Gazzetta Chimica Italiana,1988,vol. 118,p. 451 - 456
[5]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2006,vol. 45,p. 450 - 455
[6]Collection of Czechoslovak Chemical Communications,1987,vol. 52,p. 766 - 774
[7]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1988,vol. 27,p. 498 - 500
[8]Journal of Pharmaceutical Sciences,1992,vol. 81,p. 149 - 154
[9]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1990,vol. 29,p. 1034 - 1040
[10]Tetrahedron Asymmetry,1995,vol. 6,p. 991 - 1000
[11]Tetrahedron Asymmetry,1997,vol. 8,p. 2497 - 2500
[12]Tetrahedron Asymmetry,1998,vol. 9,p. 2799 - 2807
[13]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2000,vol. 39,p. 329 - 333
[14]European Journal of Pharmaceutical Sciences,2002,vol. 17,p. 121 - 130
[15]Journal of the Indian Chemical Society,2004,vol. 81,p. 778 - 780
[16]Archiv der Pharmazie,2007,vol. 340,p. 88 - 94
[17]Patent: US5700947,1997,A
[18]Journal of Molecular Catalysis B: Enzymatic,2010,vol. 62,p. 235 - 241
[19]Patent: WO2004/18487,2004,A1 .Location in patent: Page 25
[20]Chemistry Letters,2011,vol. 40,p. 1004 - 1006
[21]Chemistry of Heterocyclic Compounds,2012,vol. 48,p. 724 - 732,9
[22]Medicinal Chemistry Research,2014,vol. 23,p. 827 - 838
[23]RSC Advances,2014,vol. 4,p. 53842 - 53853
[24]PLoS ONE,2015,vol. 10
[25]ACS Medicinal Chemistry Letters,2015,vol. 6,p. 1086 - 1090
[26]Chemical Communications,2015,vol. 51,p. 14929 - 14932
[27]Medicinal Chemistry Research,2017,vol. 26,p. 672 - 679
[28]Chemical Communications,2017,vol. 53,p. 10366 - 10369
[29]Journal of Organic Chemistry,2019,vol. 84,p. 10221 - 10236
[30]International Journal of Molecular Sciences,2019,vol. 20

9
[ 30012-51-2 ]
[ 23981-80-8 ]

Yield	Reaction Conditions	Operation in experiment
63%	With formic acid; sulfuric acid; In water; ethyl acetate; toluene;	REFERENCE EXAMPLE 2 150 mg of methyl d-alpha-(6-methoxynaphth-2-yl)propionate ([alpha]D20 =+77.4) was dissolved in a mixed solution of 3.0 g of formic acid, 0.3 g of water and 0.3 g of concentrated sulfuric acid, and the solution was heated at 40 C. for 6 hours. Water was added thereto, and the solution was extracted with a mixture of toluene and ethylacetate. The organic extracts were combined, and extracted three times with an aqueous sodium hydroxide solution. The organic layer was concentrated, and 60.1 mg of the starting material was thereby recovered. The alkaline layer was acidified with 10% hydrochloric acid, extracted with ethyl acetate and concentrated under reduced pressure, whereupon 89.2 mg of d-alpha-(6-methoxynaphth-2-yl)propionic acid was obtained as colourless crystals. The yield was 63%. The optical rotation was [alpha]D20 =+58.9 and the optical purity was 88%. m.p.; 156 to 157 C. NMR (CDCl3) delta; 1.57 (3H, d, 7 Hz), 3.83 (1H, q, 7 Hz), 3.86 (3H, s), 6.9-8.05 (6H, m), 8.0 (1H, broad s) IR (KBr); 2930, 1690, 1595, 1380, 1260, 1223, 1027, 920, 853, 820, 673, 480 cm-1 MS(m/e); 230 (93, M+), 185 (100)
	With hydrogenchloride; sodium hydroxide; In methanol;	EXAMPLE 19 To a mixture of 20 g. of sodium hydroxide and 400 ml. of methanol are added 24.5 g. of methyl 6methoxy-2-naphthyl-alpha -methylacetate. The resulting reaction mixture is heated to 60C for five hours. The cooled mixture is neutralized by the addition of aqueous 1N hydrochloric acid and extracted with methylene chloride. The extracts are combined, washed with water to neutrality, dried over sodium sulfate, filtered, and evaporated to give 6-methoxy-2naphthyl-alpha-methylacetic acid. Similarly, the other 2-naphthylacetic acid ester derivatives prepared by means of the procedures described in the other examples herein are hydrolyzed to the corresponding 2-naphthylacetic acid derivatives.

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1982,p. 2575 - 2582
[2]Journal of the Chemical Society. Perkin transactions I,1994,p. 1323 - 1328
[3]Organic Letters,2019,vol. 21,p. 3299 - 3303
[4]Patent: US4417070,1983,A
[5]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1990,vol. 29,p. 304 - 309
[6]Synthesis,1985,p. 436 - 437
[7]Journal of Organic Chemistry,1983,vol. 48,p. 4658 - 4661
[8]Tetrahedron Letters,1982,vol. 23,p. 1385 - 1386
[9]Tetrahedron,1994,vol. 50,p. 1243 - 1260
[10]Bioorganic chemistry,2002,vol. 30,p. 276 - 284
[11]Patent: US3978116,1976,A
[12]Organic Syntheses,1999,vol. 76,p. 169 - 169

10
[ 31220-35-6 ]
[ 23981-80-8 ]

Yield	Reaction Conditions	Operation in experiment
97%		According to the literature procedure, a 50 mL, two-necked, round-bottomed flask was charged with ethyl 2-(6-methoxynaphthalen-2-yl)propanoate (700 mg, 2.75 mmol) and ethanol (4 mL). Then, a solution of sodium hydroxide (2.76 mmol) in ethanol (9 mL) was added slowly over 5 min. The mixture was stirred at reflux for about 3 h. After cooling the mixture to 0 C, the pH value was adjusted to 2 by adding 1 N hydrogen chloride. Standard extractive workup with ethyl acetate (3×25 mL) gave the title product as a white solid (637 mg; yield=97%). 1H NMR (300 MHz, CDCl3, 293 K, TMS): delta 10.03 (s, 1H), 7.70 (d, J=8.7 Hz, 3H), 7.41 (dd, J=8.4, 1.8 Hz, 1H), 7.12 (dt, J=7.5, 2.4 Hz, 2H), 3.91 (s, 3H), 3.89-3.82 (m, 1H), 1.58 (d, J=7.2 Hz, 3H). 13C NMR (75 MHz, CDCl3, 293 K, TMS): delta 180.25, 157.73, 134.91, 133.83, 129.30, 128.92, 127.24, 126.19, 126.14, 119.04, 105.64, 55.31, 45.22, 18.14. MS found: 230.09.
95%	With hydrogenchloride; sodium hydroxide; In ethanol; water; toluene;	REFERENCE EXAMPLE 5 Preparation of alpha-(6-methoxynaphth-2-yl) propionic acid Dissolved in 3.0 g of ethyl alcohol was 0.95 g of ethyl alpha(6-methoxynaphth-2-yl) propionate, and 1.0 g of water and 0.16 g of sodium hydroxide were added thereto. The mixture was refluxed under heating for 15 minutes. Then, 2 g of water and 5 g of toluene were added and phase separation was conducted. To the water layer thereby obtained, 15 g of toluene and 1.35 g of concentrated hydrochloric acid were added, and phase separation was conducted at 70 C. After washing with water, the organic layer was concentrated under reduced pressure, whereupon 0.80 g of almost colourless crystals were obtained. The yield was 95%. These crystals were recrystallized once from toluene to obtain a test sample for analyses. The analytical values of this product was as indicated below, and corresponded pretty well to those of the standard sample of alpha-(6-methoxynaphth-2-yl) propionic acid. Melting point: 156.8 to 157.3 C. NMR (CDCl3): delta1.57 (3H, d, 7 Hz), 3.83 (1H, q, 7 Hz), 3.86 (3H, s), 6.9~8.05 (6H, m), 8.0 (1H, broad, s). IR (KBr): 2930, 1690, 1595, 1380, 1260, 1223, 1027, 920, 853, 820, 673, 480 cm-1.

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1982,p. 2575 - 2582
[2]Tetrahedron,2012,vol. 68,p. 2113 - 2120
[3]Tetrahedron Letters,1983,vol. 24,p. 1531 - 1534
[4]Patent: US4577025,1986,A
[5]Organic Letters,2012,vol. 14,p. 3268 - 3271

11
[ 76145-94-3 ]
[ 2700-47-2 ]
[ 23981-80-8 ]
[ 146805-96-1 ]

Reference： [1]Tetrahedron,1994,vol. 50,p. 1243 - 1260

12
[ 23981-80-8 ]
[ 22204-53-1 ]
[ 23979-41-1 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium acetate;Resolution of racemate;Purification / work up;	Enantiomers of test racemates TR 19-23, of known drugs from the non-steroidal antiinflammatory group, were separated on analytical HPLC columns (250 mm x 4,6 mm), filled with CSP-4 or CSP-3. Since these compounds are structurally free carboxyl acids, it was necessary to use a polar mobile phase containing a certain amount of ammonium acetate. Results obtained by the enantioselective separation of these compounds are shown in Table 5 and the chromatogram achieved for the enantiomers of naproxen is shown in Figure 8. <n="20"/>TABLE 5 Enantiomer separations for test racemate TR 20-23 on the column filled withCSP-3 (250 mm x 4.6 mm ID), with hexane : 2-PrOH = 8:2 + lg/L NH4OAc as the mobile phase, 1 ml/min, 254 nm.

Reference： [1]Tetrahedron Asymmetry,2001,vol. 12,p. 3015 - 3018
[2]Analytical chemistry,1995,vol. 67,p. 2088 - 2095
[3]Patent: WO2009/109792,2009,A1 .Location in patent: Page/Page column 18; Figure 8
[4]Chirality,2010,vol. 22,p. 479 - 485
[5]Chemistry Letters,2011,vol. 40,p. 266 - 267
[6]RSC Advances,2016,vol. 6,p. 24835 - 24842
[7]Chemical Communications,2017,vol. 53,p. 1470 - 1473
[8]Chemical Communications,2017,vol. 53,p. 509 - 512
[9]Angewandte Chemie - International Edition,2019,vol. 58,p. 11479 - 11482
Angew. Chem.,2019,vol. 131,p. 11603 - 11606,4

13
[ 23981-47-7 ]
[ 74-88-4 ]
[ 23981-80-8 ]

Reference： [1]Journal of medicinal chemistry,1970,vol. 13,p. 203 - 205
[2]Journal of the American Chemical Society,2011,vol. 133,p. 11936 - 11939

14
[ 23981-80-8 ]
[ 23979-41-1 ]

Reference： [1]Chemistry Letters,1997,p. 555 - 556
[2]Tetrahedron Asymmetry,1995,vol. 6,p. 991 - 1000
[3]Gazzetta Chimica Italiana,1988,vol. 118,p. 451 - 456
[4]Collection of Czechoslovak Chemical Communications,1987,vol. 52,p. 766 - 774
[5]ACS Medicinal Chemistry Letters,2012,vol. 3,p. 759 - 763

15
[ 201230-82-2 ]
[ 63444-51-9 ]
[ 23981-80-8 ]
[ 3453-40-5 ]

Reference： [1]Chemical Communications,2000,p. 1239 - 1240

16
[ 201230-82-2 ]
[ 63444-51-9 ]
[ 23981-80-8 ]

Yield	Reaction Conditions	Operation in experiment
98.8%	With water; toluene-4-sulfonic acid; triphenylphosphine; lithium chloride;1% Rh/C; In butanone; at 115℃; under 41372.9 Torr;	EXAMPLE 70 [00485] A 50 ml stirred autoclave was charged with the following reactants [00486] <strong>[63444-51-9]1-(6-methoxy-2-naphthyl)ethene</strong>: 2.5 g [00487] 1% Rh/C: 0.1 g [00488] triphenyl phosphine: 0.08165 g [00489] p-toluene sulphonic acid: 1.065 g [00490] LiCl: 0.2365 g [00491] H2O: 1.2 ml [00492] Methyl ethyl ketone: 21.5 ml. [00493] The contents of the autoclave were flushed with nitrogen and then many times with carbon monoxide. Thereafter, the contents were heated to 115 C. After the temperature is attained, the autoclave was pressurised to 800 psig with carbon monoxide, stirring started and it was observed that gas absorption commenced immediately. For synthesis of naproxen, the pressure in the autoclave was maintained constant using carbon monoxide and the progress of the reaction was monitored by observing the pressure drop and by liquid sampling. The reaction was continued until the pressure drop was too low. The reactor was then cooled and the liquid phase analyzed by gas chromatography. [00494] The GC analysis showed TOF of 120 h-1 and 98% conversion of <strong>[63444-51-9]1-(6-methoxy-2-naphthyl)ethene</strong> with naproxen selectivity of 98.8%. The catalyst was filtered out and the solvent evaporated and the reaction mixture re-dissolved in toluene. The precipitated solid portion, which is a mixture of LiCl and lithium salt of p-toluene sulphonic acid was filtered out. The filtrate was treated with saturated solution of sodium bicarbonate two-three times and the aqueous phase separated to obtain the sodium salt of naproxen, which on hydrolysis with acid and extraction with dichloromethane, evaporation and vacuum distillation gives the pure product.
	With toluene-4-sulfonic acid; lithium chloride;bis-triphenylphosphine-palladium(II) chloride; In water; butanone; at 115℃; under 42133 Torr;Product distribution / selectivity;	A 20 ml stirred autoclave was charged with the following reactants 6-methoxynaphthyl ethene: 0.02808 mol PdCl2(PPh3)2: 5.6×10-5 mol p-toluene sulphonic acid: 0.0056 LiCl: 0.0056 mol H2O: 1.25 mL Methyl ethyl ketone: 19 mL The contents of the autoclave were flushed with nitrogen and then many times with carbon monoxide. Thereafter, the contents were heated to 115 C. After the temperature is attained, the autoclave was pressurized to 800 psig with carbon monoxide, stirring started and it was observed that gas absorption commenced immediately. For synthesis of naproxen, the pressure in the autoclave was maintained constant using carbon monoxide and the progress of the reaction was monitored by observing the pressure drop and by liquid sampling. The reaction was continued until the pressure drop was too low. The reactor was then cooled and the final reaction mixture analyzed by gas chromatography. The GC analysis showed TOF of 150 h-1 and 99% conversion of 6-methoxynaphthyl ethene with naproxen selectivity of 98% and n/iso ratio of 0.0204. The solvent was evaporated and the reaction mixture was re-dissolved in toluene. The solid portion, which is a mixture of LiCl and lithium salt of p-toluene sulphonic acid was filtered out. The filtrate is treated with saturated solution of sodium bicarbonate two to three times and the aqueous phase was separated which on hydrolysis with acid and extraction with dichloromethane and column separation gave pure naproxen product.

Reference： [1]Patent: US6660883,2003,B1 .Location in patent: Page column 31-32
[2]Organic Letters,1999,vol. 1,p. 459 - 461
[3]Journal of Molecular Catalysis A: Chemical,2010,vol. 330,p. 18 - 25
[4]Patent: US2005/283020,2005,A1 .Location in patent: Page/Page column 8-9

17
[ 63444-51-9 ]
[ 23981-80-8 ]

Reference： [1]Journal of Organic Chemistry,1985,vol. 50,p. 5370 - 5372
[2]Organic Letters,2015,vol. 17,p. 3544 - 3547

18
[ 2700-47-2 ]
[ 23981-80-8 ]

Yield	Reaction Conditions	Operation in experiment
51.5 g		(1) Chlorination reaction:Into a 1000 ml reactor, put 60 g of 6-methoxy-2-propanoylnaphthalene and 500 g of methanol.150g copper chloride and 50g water, heated to 60C for 15 hours,follow up to the end of the reaction, add 200 water, and recover the methanol by distillation.Add 100 g of hydrochloric acid and 450 g of toluene, stir to dissolve, and separate the layers.The water layer is deoxidized to recover copper chloride, and the organic layer is directly used for the next synthesis;(2) Ketal reaction: Add the toluene solution obtained in the previous step, 45g of neopentyl glycol and 2g of p-toluenesulfonic acid into a 1000ml reactor, heat up to reflux for 6 hours, sample and track until the end of the reaction, cool to room temperature, and wash to obtain ketal toluene solution;(3) Rearrangement reaction: Add a ketal toluene solution to a 1000 ml reactor, and heat and reflux with water, add 2 g of zinc oxide, and then heat and reflux for 10 hours.Sampling and tracking until the end of the reaction, cooling and washing with water to obtain a rearranged toluene solution;(4) Hydrolysis and acidification: Add a rearranged toluene solution to a 1000ml reactor, add 100g of water, heat up and remove toluene, cool down, add 40% sodium hydroxide solution, react for 2 hours, pour into 3000ml water, and acidify by adding dropwise hydrochloric acid. Adjust pH = 1-2, suction filter, wash with water, and dry to obtain 51.5g of D,L-naproxen with a content of 95.8%.

Reference： [1]Chemical and Pharmaceutical Bulletin,1983,vol. 31,p. 3139 - 3148
[2]Chemical and Pharmaceutical Bulletin,1983,vol. 31,p. 3139 - 3148
[3]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1990,vol. 29,p. 304 - 309
[4]Patent: CN109485561,2019,A
[5]Patent: CN109485561,2019,A
[6]Patent: CN110183323,2019,A
[7]Patent: CN110256228,2019,A .Location in patent: Paragraph 0025-0029

19
[ 201230-82-2 ]
[ 108781-65-3 ]
[ 23981-80-8 ]

Yield	Reaction Conditions	Operation in experiment
99%	With water; toluene-4-sulfonic acid; triphenylphosphine; lithium chloride;1% Rh/C; In butanone; at 115℃; under 41372.9 Torr;	[01047] A 50 ml stirred autoclave was charged with the following reactants [01048] 1-(6-methoxy-2-naphthyl)ethanol: 1 g [01049] 1% Rh/C: 0.1 g [01050] triphenyl phosphine: 0.08165 g [01051] p-toluene sulphonic acid: 0.5 g [01052] LiCl: 0.1 g [01053] H2O: 1.2 ml [01054] Methyl ethyl ketone: 21.5 ml. [01055] The contents of the autoclave were flushed with nitrogen and then many times with carbon monoxide. Thereafter, the contents were heated to 115 C. After the temperature is attained, the autoclave was pressurised to 800 psig with carbon monoxide, stirring started and it was observed that gas absorption commenced immediately. For synthesis of naproxen, the pressure in the autoclave was maintained constant using carbon monoxide and the progress of the reaction was monitored by observing the pressure drop and by liquid sampling. The reaction was continued until the pressure drop was too low. The reactor was then cooled and the liquid phase analyzed by gas chromatography. [01056] The GC analysis showed TOF of 100 h-1 and 96% conversion of 6 methoxy naphthyl ethanol with naproxen selectivity of 99%. The catalyst was filtered out and the solvent evaporated and the reaction mixture re-dissolved in toluene. The precipitated solid portion, which is a mixture of LiCl and lithium salt of p-toluene sulphonic acid was filtered out. The filtrate was treated with saturated solution of sodium bicarbonate two-three times and the aqueous phase separated, which on hydrolysis and extraction with dichloromethane gives the pure product.
98.9%	With water; toluene-4-sulfonic acid; triphenylphosphine; lithium chloride;1% Pd/C; In butanone; at 115℃; under 41372.9 Torr;	[00959] A 50 ml stirred autoclave was charged with the following reactants [00960] 1-(6-methoxy-2-naphthyl)ethanol: 1 g [00961] 1% Ru/C: 0.1 g [00962] triphenyl phosphine: 0.08165 g [00963] p-toluene sulphonic acid: 1.065 g [00964] LiCl: 0.2365 g [00965] H2O: 1.2 ml [00966] Methyl ethyl ketone: 21.5 ml. [00967] The contents of the autoclave were flushed with nitrogen and then many times with carbon monoxide. Thereafter, the contents were heated to 115 C. After the temperature is attained, the autoclave was pressurised to 800 psig with carbon monoxide, stirring started and it was observed that gas absorption commenced immediately. For synthesis of naproxen, the pressure in the autoclave was maintained constant using carbon monoxide and the progress of the reaction was monitored by observing the pressure drop and by liquid sampling. The reaction was continued until the pressure drop was too low. The reactor was then cooled and the liquid phase analyzed by gas chromatography. [00968] The GC analysis showed TOF of 130 h-1 and 99% conversion of 6 methoxy naphthyl ethanol with naproxen selectivity of 98.9%. The catalyst was filtered out and the solvent evaporated and the reaction mixture re-dissolved in toluene. The precipitated solid portion, which is a mixture of LiCl and lithium salt of p-toluene sulphonic acid was filtered out. The filtrate was treated with saturated solution of sodium bicarbonate two-three times and the aqueous phase separated, which on hydrolysis and extraction with dichloromethane gives the pure product.
97%	With toluene-4-sulfonic acid; triphenylphosphine; lithium chloride;1% Pd/C; In water; butanone; at 115℃; under 41372.9 Torr;	EXAMPLE 26 [00113] A 50 ml stirred autoclave was charged with the following reactants [00114] 1-(6 methoxy-2-naphthyl)ethanol: 1 g [00115] 1% Pd/C: 0.1 g [00116] triphenyl phosphine: 0.08165g [00117] p-toluene sulphonic acid: 1.065 g [00118] LiCl: 0.2365 g [00119] H2O: 1.2 ml [00120] Methyl ethyl ketone: 21.5 ml. [00121] The contents of the autoclave were flushed with nitrogen and then many times with carbon monoxide. Thereafter, the contents were heated to 115 C. After the temperature is attained, the autoclave was pressurised to 800 psig with carbon monoxide, stirring started and it was observed that gas absorption commenced immediately. For synthesis of naproxen, the pressure in the autoclave was maintained constant using carbon monoxide and the progress of the reaction was monitored by observing the pressure drop and by liquid sampling. The reaction was continued until the pressure drop was too low. The reaction was then cooled and the liquid phase analysed by gas chromatography. [00122] The GC analysis showed TOF of 300 h-1 and 99% conversion of 1-(6-methoxy-2-naphthyl)ethanol with naproxen selectivity of 97%. The catalyst was filtered out and the solvent evaporated and the reaction mixture re-dissolved in toluene. The precipitated solid portion, which is a mixture of LiCl and lithium salt of p-toluene sulphonic acid was filtered out. The filtrate is treated with a saturated solution of sodium bicarbonate two-three times and the aqueous phase is separated to obtain the sodium salt of naproxen.

With toluene-4-sulfonic acid; lithium chloride;bis-triphenylphosphine-palladium(II) chloride; In water; butanone; at 115℃; under 42133.0 Torr;Product distribution / selectivity;

A 50 ml stirred autoclave was charged with the following reactants 1-(6'-methoxynaphthyl)ethanol: 0.02808 mol PdCl2(PPh3)2: 5.6×10-5 mol p-toluene sulphonic acid: 0.0056 LiCl: 0.0056 mol H2O: 1.25 mL Methyl ethyl ketone: 19 mL The contents of the autoclave were flushed with nitrogen and then many times with carbon monoxide. Thereafter, the contents were heated to 115 C. After the temperature is attained, the autoclave was pressurized to 800 psig with carbon monoxide, stirring started and it was observed that gas absorption commenced immediately. For synthesis of naproxen, the pressure in the autoclave was maintained constant using carbon monoxide and the progress of the reaction was monitored by observing the pressure drop and by liquid sampling. The reaction was continued until the pressure drop was too low. The reactor was then cooled and the final reaction mixture analyzed by gas chromatography. The GC analysis showed TOF of 425 h-1 and 99% conversion of 1-(6'-methoxynaphthyl) ethanol with naproxen selectivity of 97.5% and n/iso ratio of 0.025. The solvent was evaporated and the reaction mixture was re-dissolved in toluene. The solid portion, which is a mixture of LiCl and lithium salt of p-toluene sulphonic acid was filtered out. The filtrate is treated with saturated solution of sodium bicarbonate two to three times and the aqueous phase was separated which on hydrolysis with acid and extraction with dichloromethane and column separation gave pure naproxen product.

Reference： [1]Patent: US6660883,2003,B1 .Location in patent: Page column 62
[2]Patent: US6660883,2003,B1 .Location in patent: Page column 57-58
[3]Patent: US6660883,2003,B1 .Location in patent: Page column 11
[4]Patent: US2005/283020,2005,A1 .Location in patent: Page/Page column 7

20
racemic 2-(6-methoxy-2-naphthyl)propionic acid [ No CAS ]
[ 23981-80-8 ]
[ 26159-34-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water; toluene;	EXAMPLE 7 The following were charged to a 12-liter, jacketed, and 3-neck reactor equipped with a mechanical agitator, a thermometer, and a condenser: 500.47 grams of 2-(6-methoxy-2-naphthyl)propionic acid assaying 88.10% S-enantiomer, 649.33 grams of 2-(6-methoxy-2-naphthyl)propionic acid assaying 99.17% S-enantiomer, 224.87 grams of 2-(6-methoxy-2-naphthyl)propionic acid assaying 99.57% S-enantiomer, 105.06 grams of racemic 2-(6-methoxy-2-naphthyl)propionic acid, 6744.25 grams of fresh toluene, and 21.64 grams of water. The mixture was heated to 85 C. to dissolve the solids. The composite solution was analyzed for chiral purity (result: 91.95% S-enantiomer). A total of 391.73 grams of 49.22 wt % NaOH was then added with the temperature being maintained below 87.5 C. Water (102.06 grams) was also added. Two clear liquid phases were obtained. Water was stripped to 94.0 C. in 369 minutes. The total amount of water collected during the strip was 293.90 grams and the amount of toluene removed was 25.07 grams. The batch was agitated at 92.9-94.0 C. for 15 minutes and cooled to 75 C. in 75 minutes. It was then held at 75 C. for 30 minutes. Solids in the slurry settled well throughout the 30-minute 75 C. ride. A total of 1840 grams of 75 C. toluene was used to rinse the reactor and to wash the wet centrifuge cake (sodium (S)-2-(6-methoxy-2-naphthyl)propionate monohydrate). Totals of 6224.1 and 1225.15 grams of mother liquor and wash liquor were recovered, respectively. An undetermined amount of product remained in the reactor and was not accounted for in the calculations of yields. The wet centrifuge cake weighed 994.74 grams which after drying for 4 hours at ambient temperature and under full vacuum yielded 959.89 grams of product. The product was dried further for 12 hours at 80-90 C. and under full vacuum. A total of 892.57 grams of dry final product (anhydrous sodium (S)-2-(6-methoxy-2-naphthyl)propionate) was obtained. Chiral purities for the product and the mother liquor were found by analysis to be 99.28% S-enantiomer and 81.40% S-enantiomer, respectively.

Reference： [1]Patent: US5874614,1999,A

21
[ 23981-80-8 ]
[ 26159-34-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In toluene;	EXAMPLE 1 A 943.08 gm solution of 14.85 wt % 2-(6-methoxy-2-naphthyl)propionic acid in toluene was charged to a 2000 mL round-bottom flask equipped with a stirrer. The stirred solution was heated to a temperature of 75-85 C. During a 10 minute period thereafter, an aqueous solution of NaOH (427.24 gm, 5.41 wt %) was slowly fed into the naproxen-toluene solution. The 2-liquid phase solution was then aged at 80 C. for 30 minutes and cooled to 40 C. over an additional 50 minute period. The phases then were allowed to separate by settling for 5 minutes. The aqueous phase (an aqueous solution of sodium naproxen) was recovered and determined to weight 562.31 gm, to contain 25.48 wt % sodium naproxen, and to have an S(+)-isomer purity of 98.15%.

Reference： [1]Patent: US5936118,1999,A

22
[ 23981-80-8 ]
[ 5394-59-2 ]
N-[1-(3,4-dichlorobenzyl)pyrrolidin-3-(RS)-ylmethyl]-2-(6-methoxynaphth-2-yl)propionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Other Examples Proceeding as described above but substituting 4-(2,5-dimethylphenyl)-4-oxobutyric acid with 2-(6-methoxynaphth-2-yl)-2-methylacetic acid gave N-[1-(3,4-dichlorobenzyl)pyrrolidin-3-(RS)-ylmethyl]-2-(6-methoxynaphth-2-yl)propionamide.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US6166015, 2000, A

23
[ 2700-47-2 ]
[ 149-73-5 ]
[ 23981-80-8 ]

Yield	Reaction Conditions	Operation in experiment
80%	With potassium hydroxide; iodine; In methanol; water;	(b) To a solution of trimethylorthoformate (14.4 ml; 0.14 mole) in methanol (40 ml; 0.99 mole) was added 0.1 ml of a 48% solution of hydrochloric in methanol and the 1-(6'-methoxy-2'-naphthyl)-1-propanone (10 g; 0.047 mole). After 10 minutes the solution became homogeneous and was maintained under reflux for 2 hours. It was then cooled to 40 C. and iodine (11.85 g; 0.047 mole) was added. The reaction mixture was refluxed for 30 hours, the solvent was removed by distillation and the residue was treated with potassium hydroxide in methanol (0.20 mole in 40 ml) at boiling for 2 hours. The reaction mixture was evaporated to dryness, dissolved in water and extracted with ethyl ether. The aqueous layer was acidified to precipitate the dl 2-(6'-methoxy-2'-naphthyl)-propionic acid weighing (after drying) 8.65 g; m.p. 154-155 C. (yield, 80%).

Reference： [1]Patent: US4608441,1986,A

24
(CHCl₃) [ No CAS ]
[ 30012-51-2 ]
[ 23981-80-8 ]

Yield	Reaction Conditions	Operation in experiment
63%	With hydrogenchloride In 1,2-dimethoxyethane; water	9 EXAMPLE 9 STR23 EXAMPLE 9 STR23 A mixture of 90 mg (0.37 mmol) of methyl (+)-α-(6-methoxy-2-naphthyl)propionate having a 100% optical purity [α]D20 +78.2° (CHCl3)], 1 ml of 12N aqueous hydrochloric acid and 1 ml of dimethoxyethane was stirred at 50° C. for 23 hours. After adding 10 ml of water, the mixture was extracted with diethyl ether (8 ml*3), and the extract was washed with water (3 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by column chromatography [silica gel, hexane+ethyl acetate (1:2)] to obtain 49 mg of (+)-α-(6-methoxy-2-naphthyl)propionic acid as colorless crystals. Yield, 63%. Melting Point: 155°-157° C. [α]D20 +67.2° (c=1.10, CHCl3).

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US4496755, 1985, A

25
[ 23981-80-8 ]
[ 61495-42-9 ]

Yield	Reaction Conditions	Operation in experiment
70%	With boron tribromide In methanol; dichloromethane; water	1 1A Methyl 2-(6-hydroxy-2-naphthyl)propionate 1A Methyl 2-(6-hydroxy-2-naphthyl)propionate Boron tribromide (70 ml, 737 mmol) was added at -78°C to a solution of 2-(6-methoxy-2-naphthyl)propionic acid (10 g, 43.4 mmol) in dry methylene chloride (130 ml). The reaction mixture was stirred at room temperature for 5 h, then 136 ml of methanol were added and stirred for 18 hours. After this time, the mixture was evaporated to dryness, water (250 ml) was added and extracted with ethyl ether (4x100 ml). The combined ether phases were dried and the solvent was evaporated off, to obtain a crude which was purified by flash chromatography through a silica gel column. Eluding with petroleum ether:ethyl ether, 9:1, 6.9 g of the title compound were obtained as a white solid with melting point 184-186°C (70% yield). 1H N.M.R. (300 MHz, CDCl3) δ ppm: 1.56 (d, 3H); 3.70 (s, 3H); 3.87 (q, 1H); 5.75 (s, 1H); 7.08 (m, 2H); 7.38 (dd, 1H); 7.60 (d, 1H); 7.66 (m, 2H).
	Multi-step reaction with 2 steps 1: hydrogen bromide / water / 2 h / Reflux; Green chemistry 2: sulfuric acid / 4 h / Reflux

Reference： [1]Current Patent Assignee: A. MENARINI - INDUSTRIE FARMACEUTICHE RIUNITE - S.R.L. - EP775133, 2001, B1
[2]Bomon, Jeroen; Bal, Mathias; Achar, Tapas Kumar; Sergeyev, Sergey; Wu, Xian; Wambacq, Ben; Lemière, Filip; Sels, Bert F.; Maes, Bert U. W. [Green Chemistry, 2021, vol. 23, # 5, p. 1995 - 2009]

26
[ 23981-80-8 ]
[ 30012-51-2 ]

Yield	Reaction Conditions	Operation in experiment
93.3%	With hydrogenchloride; sodium hydrogencarbonate;aluminium trichloride; In dichloromethane; water; 1,3,5-trimethyl-benzene;	EXAMPLE 15 d-2-(6-Methoxy-2-naphthyl)propionic acid, methyl ester 20.8 Ml of mesitylene are added to a solution of 32.3 g of the methyl ester of the d-2-(6-methoxy-2-naphthyl) propionic acid dissolved in 130 ml of methylene chloride. 20 Grams of anhydrous aluminum chloride are added portionwise under stirring to the reaction mixture cooled to -5C, while keeping the temperature at about 10C. The reaction mixture is kept under stirring for one hour at about 10C and then is poured into a mixture made of 100 g of crushed ice and of 15 ml of a 35% (w/v) aqueous solution of hydrochloric acid. The layers are separated after 15 minutes of stirring, the aqueous phase is discarded while the organic layer is twice washed with 100 ml of a 1 N aqueous solution of hydrochloric acid, once with 100 ml of water and once with 100 ml of a 8% (w/v) aqueous solution of sodium bicarbonate. The organic solution is dried over anhydrous sodium sulfate and concentrated to dryness under vacuum. The residue is crystallized by n-hexane obtaining 22.8 g of pure product having (C = 1% in chloroform) with a yield equal to 93.3%.

Reference： [1]Patent: EP440930,1991,A2

27
[ 23981-80-8 ]
[ 62784-66-1 ]
(R)-naproxen di(1-naphthyl)methyl ester [ No CAS ]
[ 1116086-50-0 ]
[ 22204-53-1 ]
[ 23979-41-1 ]

Yield	Reaction Conditions	Operation in experiment
	With benzoic acid anhydride; N-ethyl-N,N-diisopropylamine;(R)-(+)-2-phenyl-2,3-dihydrobenzo[d]imidazo[2,1-b]thiazole; In dichloromethane; at 20℃; for 6h;Resolution of racemate;Product distribution / selectivity;	Experimental Example 8Production of Optically Active Ester and Optically Active Carboxylic Acid Using Naproxen (Optical Resolution of Naproxen) As shown by the above reaction equation, an optically active ester and optically active carboxylic acid are obtained by reacting 1,1-di(1-naphthyl)methanol or 1,1-di(9-phenanthryl)methanol and racemic naproxen. The results are shown in Table 8.; Entry 53(R)-naproxen di(1-naphthyl)methylesterHPLC (CHIRALPAK AD-H, i-PrOH/hexane=1/9, flow rate=1.0 mL/ml): tR=13.7 min (10.6%), tR=17.4 min (89.4%);IR (neat): 3034, 1733, 1604, 1508, 782, 679 cm-1;1H NMR (CDCl3): delta8.29 (s, 1H, 1'-H), 8.00-7.90 (m, 1H, Ph), 7.82-6.96 (m, 17H, Ph), 6.95-6.81 (m, 2H, Ph), 3.86 (q, J=7.0 Hz, 1H, 2-H), 3.79 (s, 3H, OMe), 1.49 (d, J=7.0 Hz, 3H, 3-H);13C NMR (CDCl3): delta173.6, 157.6, 135.1, 134.7, 134.5, 133.8, 133.7, 133.6, 131.2, 130.8, 129.3, 129.1, 128.9, 128.8, 128.7, 128.6, 128.3, 127.1, 126.7, 126.5, 126.3, 126.2, 125.8, 125.6, 125.3, 125.2, 125.0, 123.4, 123.3, 118.9, 105.5, 71.2, 55.2, 45.5, 18.3;HR MS: calculated for C35H28O3Na (M+Na+)=519.1931; found 519.1932.

Reference： [1]European Journal of Organic Chemistry,2008,p. 5887 - 5890
[2]Journal of the American Chemical Society,2010,vol. 132,p. 11629 - 11641
[3]Journal of the American Chemical Society,2010,vol. 132,p. 11629 - 11641
[4]Patent: US2010/234610,2010,A1 .Location in patent: Page/Page column 13-14

28
[ 23981-80-8 ]
[ 62784-66-1 ]
[ 1116086-50-0 ]
[ 22204-53-1 ]
[ 23979-41-1 ]

Reference： [1]European Journal of Organic Chemistry,2008,p. 5887 - 5890
[2]Journal of the American Chemical Society,2010,vol. 132,p. 11629 - 11641

29
[ 23981-80-8 ]
potassium 4-acetylphenyltrifluoroborate [ No CAS ]
C₂₂H₂₀O₄ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2008,vol. 130,p. 17676 - 17677

30
[ 23981-80-8 ]
[ 18107-18-1 ]
[ 30012-51-2 ]

Yield	Reaction Conditions	Operation in experiment
	With methanol In hexane; benzene at 20℃; for 0.166667h;

Reference： [1]Location in patent: experimental part Noji, Masahiro; Sunahara, Haruka; Tsuchiya, Ken-Ichi; Mukai, Toru; Komasaka, Ayako; Ishii, Keitaro [Synthesis, 2008, # 23, p. 3835 - 3845]

31
[ 107-35-7 ]
[ 23981-80-8 ]
[ 1191076-35-3 ]

Yield	Reaction Conditions	Operation in experiment
90%		Example 2: 2-{ [2- (6-methoxy-2-naphthyl) propanoyl] amide} ethanesulfonic acid (Compound 63) synthesisOne gram of <strong>[23981-80-8]naproxen</strong> is solubilized in DMF previously dried out under molecular screen cleaner. Sequentially, an ice bath, 0.8 mL of diethylcyanophosphonate (DEPC), 1.085 g of taurine and 7.0 mL of previously dried out under molecular screen cleaner triethylamine are added. The reaction is kept for 2 hours shaking at room temperature.At end of the reaction, the base excess is removed through nitrogen pull-down, and the remaining solvent is eliminated through evaporation at reduced pressure. The obtained residue is added, in small portions, to a saturated aqueous cold NaHCO3 solution. The formed precipitated is collected by filtration, washed with a small portion of cold water and dried out under phosphorus pentoxide. The obtained dry mass is grinded under THF, with the solid residue being filtrated and dried out and calculated yield of around 90% (analyzed by HPLC) .After the purification of the product, the study of structural confirmation led to the result of Table 3.Table 3: Structural characterization of the resulting Compound from the reaction between taurine and <strong>[23981-80-8]naproxen</strong> (Compound 63) <n="54"/>

Reference： [1]Patent: WO2009/124371,2009,A2 .Location in patent: Page/Page column 51

32
[ 26117-28-2 ]
[ 23981-80-8 ]
(S,S)-N-acetyl-S-(6-methoxy-α-methyl-2-naphthalen acetyl)cisteine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: naproxen With 1,1'-carbonyldiimidazole In DMF (N,N-dimethyl-formamide); chloroform for 0.25h; Stage #2: (S)-N-acetylcysteine In DMF (N,N-dimethyl-formamide); chloroform at 20℃; for 12h;	1.a To a solution of 6-methoxy-α-methyl-2-naphthalenacetic acid (10 g, 43.4 mmoles) in chloroform (100 ml) and N,N-dimethylformamide (6 ml), 1,1'-carbonyldiimidazole (CDI) (7.04 g, 43.4 mmoles) is added. After 15 minutes the obtained solution is treated with (S)-N-acetylcisteine (7.08 g, 43.4 mmoles) and left at room temperature for 12 hours. The reaction mixture is washed with HCl 5%, then with water and lastly with brine. The organic phase is anhydrified with sodium sulphate and then evaporated at reduced pressure. The obtained residue is purified by chromatography on silica gel eluting with ethyl acetate. 11.66 g of the expected product in the form of a white solid m.p.: 122°-1260° C., is obtained.1H-NMR (CDCl3): 7.71-7.65 (3H, m), 7.34, (1H, dd), 7.16-7.09 (2H, m), 6.36 (1H, d), 4.67 (1H, m), 4.00 (1H, q), 3.90 (3H, s) 3.32 (2H, t), 1.84 (3H, s), 1.59 (3H, d).

Reference： [1]Current Patent Assignee: NICOX S.A. - US6869974, 2005, B1 Location in patent: Page/Page column 33-34

33
[ 23981-80-8 ]
[ 110282-71-8 ]
[ 1187670-15-0 ]
(S)-naproxen di(9-phenanthryl)methyl ester [ No CAS ]
[ 22204-53-1 ]
[ 23979-41-1 ]

Yield	Reaction Conditions	Operation in experiment
	With benzoic acid anhydride; N-ethyl-N,N-diisopropylamine;(R)-(+)-2-phenyl-2,3-dihydrobenzo[d]imidazo[2,1-b]thiazole; In dichloromethane; at 20℃; for 6h;Resolution of racemate;Product distribution / selectivity;	Entry 55To a dichloromethane solution (2.0 mL) containing benzoic anhydride (54.3 mg, 0.240 mmol) and racemic naproxen (46.1 mg, 0.200 mmol); diisopropylethylamine (62.7 muL, 0.360 mmol), benzotetramisole (2.5 mg, 0.010 mmol), and 1,1-di(9-phenanthryl)methanol (38.4 mg, 0.100 mmol) were added in order at room temperature. After stirring the reaction mixture solution at room temperature for 6 hr, the reaction was stopped with saturated ammonium chloride water. After fractionating the organic layer, the aqueous layer was extracted 4 times with dichloromethane. After combining the organic layers, they were dried with anhydrous sodium sulfate. After filtering the solution, it was vacuum concentrated, and the obtained mixture was fractionated by thin layer silica gel chromatography to obtain the corresponding optically active naproxen ester (59.7 mg, 50%, 88% ee) and the unreacted optically active naproxen (12.6 mg, 27%, 61% ee).(R)-naproxen di(9-phenanthryl)methylesterHPLC (CHIRALCELL OD-H, i-PrOH/hexane=1/4, flow rate=0.75 mL/mi): tR=23.7 min (94.1%), tR=41.1 min (5.9%);IR (KBr): 3063, 1731, 1605, 1265, 1028, 749, 727 cm-1;1H NMR (CDCl3): delta8.84-8.50 (m, 4H, Ph), 8.43 (s, 1H, 1'-H), 8.25-8.12 (m, 1H, Ph), 7.80-7.08 (m, 18H, Ph), 6.83-6.75 (m, 1H, Ph), 4.03 (q, J=7.1 Hz, 1H, 2-H), 3.96 (s, 3H, OMe), 1.64 (d, J=7.1 Hz, 3H, 3-H);13C NMR (CDCl3): delta173.5, 157.9, 135.2, 134.0, 132.9, 132.6, 131.0, 130.9, 130.6, 130.6, 130.3, 130.2, 129.8, 129.5, 129.1, 129.0, 128.9, 128.3, 128.0, 127.4, 127.3, 127.2, 126.8, 126.6, 126.6, 126.5, 126.4, 126.3, 126.2, 124.2, 123.9, 123.4, 123.1, 122.4, 122.2, 119.0, 105.6, 71.0, 55.4, 45.7, 18.0.(S)-naproxenHPLC (CHIRALPAK AD-H, i-PrOH/hexane/TFA=1/10/0.01, flow rate=1.0 mL/min); tR=13.8 min (18.9%), tR=15.8 min (81.1%);1H NMR (CDCl3): delta9.42 (br s, 1H, COOH), 7.68-7.55 (m, 3H, Ph), 7.33-7.28 (m, 1H, Ph), 7.13-6.99 (m, 2H, Ph), 3.83 (s, 3H, OMe), 3.79 (q, J=7.2 Hz, 1H, 2-H), 1.50 (d, J=7.2 Hz, 3H, 3-H).

Reference： [1]Patent: US2010/234610,2010,A1 .Location in patent: Page/Page column 13-14
[2]Tetrahedron Letters,2010,vol. 51,p. 5666 - 5669

34
[ 67-56-1 ]
[ 23981-80-8 ]
[ 22204-53-1 ]
[ 23979-41-1 ]
[ 81623-44-1 ]
[ 26159-35-3 ]

Reference： [1]Journal of Molecular Catalysis B: Enzymatic,2010,vol. 65,p. 49 - 51
[2]Journal of Molecular Catalysis B: Enzymatic,2010,vol. 65,p. 49 - 51

35
[ 23981-80-8 ]
[ 19408-84-5 ]
[ 1224428-91-4 ]

Yield	Reaction Conditions	Operation in experiment
65.1%	With dmap; dicyclohexyl-carbodiimide In dichloromethane at 30 - 35℃;

Reference： [1]Location in patent: experimental part Qian, Hai; Fu, Zhixian; Zhang, Huibin; Zhou, Jinpei; Huang, Wenlong; Jin, Jing; Chen, Wei; Dai, Dongyan [Letters in drug design and discovery, 2010, vol. 7, # 2, p. 122 - 127]

36
[ 1443679-54-6 ]
[ 23981-80-8 ]

Yield	Reaction Conditions	Operation in experiment
78%	With acetic acid; sodium nitrite; In dimethyl sulfoxide; at 90 - 100℃;	A mixture of2-methoxy-6-(1-nitropropan-2-yl) naphthalene (20 g, 0.081 mol), sodium nitrite(16.8 g, 0.245 mol), and acetic acid (49 g, 0.81 mol) in DMSO (160 mL) was heated to 90 to 100 C for 22-24 h. On the completion of the reaction (TLC),the reaction mass was quenched into 10% hydrochloric acid (200 mL), stirredabout 15 min, product was extracted into toluene (3 X 100 mL), The mixture of above organic layer and water (100mL), stirred about 15 min at 25 to 35 C, adjusted pH 13-14 with caustic lye(30 mL), separated the toluene and washed with toluene (50 mL). The aqueous layer was separated, adjusted thepH to 3-4 with concentrated sulfuric acid (14 mL), and stirred about 30 min at 60-65 C. the solid material was filtered, washed with water (40 mL), and driedat 80 C to constant weight to afford RS(+) 2-(6-methoxynaphthalen-2-yl) propionic acid (2, 14.6 g, 78%) after crystallization from toluene. MP:155 to 158 C; 1HNMR (400 MHz, DMSO-d6) delta 7.66 - 7.68 (d,3H, J=8.8Hz), 7.39 (dd, 1H, J=1.5Hz, J=8.3Hz), 7.08 - 7.13 (m, 2H), 3.8 (s, 3H), 3.82 - 3.86 ( m, 1H),1.56 (d, 3H, J=6.8); 13CNMR (400 MHz, CDCl3): delta 180.91, 157.65, 134.83, 133.77,129.27, 128.84, 127.20, 126.16, 126.11, 119.01, 105.52, 55.27, 45.21, 18.10;MS: calcd for C14H14O3 230 (M+),found 231(MH+); IR (KBr) 3201.02 cm-1 (OH), 1728cm-1 (C=O), 3002.9 cm-1 (aromatic CH),855.66 cm-1 (C=C), 1264.69 cm-1 (CO).

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 3911 - 3915

37
[ 3453-33-6 ]
[ 23981-80-8 ]

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 3911 - 3915
[2]Journal of Organic Chemistry,2018,vol. 83,p. 11860 - 11872

38
[ 6340-03-0 ]
[ 23981-80-8 ]
2-(1H-benzo[d]imidazol-1-yl)ethyl 2-(6-methoxynaphthalen-2-yl)propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88.8%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In tetrahydrofuran; at 20℃; for 62.5h;Inert atmosphere; Cooling with ice;	Example 17: DPX-2-0006 (JBX017) 2-(1H-benzo[d]imidazol-1-yl)ethyl 2-(6-methoxynaphthaen-2-yl)propanoate. 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide-HCI (EDC-HCI) (2.20 g, 11.5 mmol) was added solid all at once to a magnetically stirred solution of <strong>[23981-80-8]naproxen</strong> (2.30 g, 10.0 mmol), 2-(1 H-benzo[d]imidazol-1 -yl)ethanol (1.62 g, 10.0 mmol) and 4- Dimethylaminopyridine (68 mg, 0.5 mmol) in dry tetrahydronfuran (50 mL) cooled in an ice bath and kept under nitrogen. The reaction mixture (slurry - EDC-HCI failed to dissolve) was stirred in an ice bath for 30 min and at ambient temperature. More EDC-HCI (400 mg, 2 mmol) was added after 3, 5 and 6 hours. After stirring for 48 hours the mixture was concentrated and the residue partitioned between water (50 mL), saturated NH4CI (20 mL) and EtOAc (120 mL). The organic layer was washed with 50 % saturated NH4CI (2 x 50 mL), 50 % saturated NaHC03 (50 mL) and brine (50 mL). The organic layer was dried and concentrated. Flash Chromatography using ethyl acetate and heptanes as eluent afforded the title compound as a colourless solid (3.33 g, 88.8 % yield ). Mp. 125.0 -125.7 C. 1H NMR (400 MHz, DMSO) delta 8.09 (s, 1 H), 7.75 (d, J = 9.0 Hz, 1 H), 7.71 (d, J = 8.5 Hz, 1 H), 7.69 - 7.63 (m, 1 H), 7.61 - 7.54 (m, 2H), 7.28 (d, J = 2.5 Hz, 1 H), 7.26 - 7.18 (m, 3H), 7.16 (dd, J = 9, 2.5 Hz, 1 H), 4.58 - 4.32 (m, 4H), 3.87 (s, 3H), 3.83 (q, J = 7 Hz, 1 H), 1.37 (d, J = 7 Hz, 3H). 13C NMR (101 MHz, DMSO) delta 173.52, 157.18, 144.13, 143.29, 135.19, 133.83, 133.29, 129.13, 128.32, 126.93, 126.09, 125.58, 122.25, 121.46, 1 19.38, 1 18.69, 1 10.37, 105.67, 63.03, 55.15, 44.36, 43.10, 18.12. DEPT 13C NMR (101 MHz, DMSO) delta 144.12, 129.13, 126.93, 126.09, 125.58, 122.25, 121.45, 1 19.37, 118.69, 1 10.36, 105.67, 63.03 (CH2), 55.14, 44.36, 43.10 (CH2), 18.12.

Reference： [1]Patent: WO2013/64153,2013,A1 .Location in patent: Page/Page column 30; 31

39
[ 1615-14-1 ]
[ 23981-80-8 ]
2-(1H-imidazol-1-yl)ethyl 2-(6-methoxynaphthalen-2-yl)propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68.3%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In tetrahydrofuran; at 20℃; for 39.5h;Inert atmosphere; Cooling with ice;	Example 16: DPX-2-0005 (JBX019) 2-( 1 H-benzo[d]imidazol- 1 -yl)ethyl 2-( 6-methoxynaphthalen-2-yl)propanoate 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide-HCI (EDC-HCI) (2.20 g, 1 1.5 mmol) was added solid all at once to a magnetically stirred solution of naproxen (2.30 g, 10.0 mmol), 1 -(2-hydroxyethyl)imidazole (1.12 g, 10.0 mmol) and 4- Dimethylaminopyridine (61 mg, 0.5 mmol) in dry tetrahydrofuran (50 mL) cooled in an ice bath and kept under nitrogen. The reaction mixture was stirred in an ice bath for 30 min and at ambient temperature. More EDC-HCI (400 mg, 2 mmol) was added after 13 hrs, 17 hrs . After stirring for 22 hrs at room temperature the mixture was concentrated and the residue partitioned between water (50 mL), saturated NH4CI (20 mL) and EtOAc (120 mL). The organic layer was washed with 50 % saturated NH4CI (2 x 50 mL), 50 % saturated NaHC03 (50 mL) and brine (50 mL). The organic layer was dried and concentrated. The oily residue was purified by Flash Chromatography using ethyl acetate and heptanes as eluent afforded a colourless oil (2.74 g, 84 %) after drying in high vacuum. The oil was crystallised from ether and recrystallised from Tert-butylmethylether (~20 mL, seeded) to afford the title compound as a colourless solid (2.21 g, 68.3 %). Mp. 60.6-61.3 C. H N R (400 MHz, DMSO) delta 7.80 (d, J = 9.0 Hz, 1 H), 7.77 (d, J = 8.5 Hz, 1 H), 7.68 (d, J = 1 Hz, 1 H), 7.51 (s, 1 H), 7.33 (dt, J = 5.5, 3 Hz, 1 H), 7.30 (d, J = 2.5 Hz, 1 H), 7.17 (dd, J = 9, 2.5 Hz, 1 H), 6.98 (t, J = 1 Hz, 1 H), 6.78 (t, J = 1 Hz, 1 H), 4.34 - 4.12 (m, 4H), 3.92 (q, J = 7 Hz, 1 H), 3.88 (s, 3H), 1.45 (d, J = 7 Hz, 3H). 3C NMR (101 MHz, DMSO) delta 173.52, 157.19, 137.40, 135.30, 133.33, 129.15, 128.37, 128.25, 126.99, 126.20, 125.63, 1 19.46, 1 18.73, 105.69, 63.74, 55.15, 44.94, 44.35, 18.19

Reference： [1]Patent: WO2013/64153,2013,A1 .Location in patent: Page/Page column 29; 30

40
[ 1558014-41-7 ]
[ 23981-80-8 ]
[ 151213-40-0 ]

Reference： [1]Asian Journal of Chemistry,2013,vol. 25,p. 8701 - 8707

41
[ 1558014-42-8 ]
[ 23981-80-8 ]
[ 151213-40-0 ]

Reference： [1]Asian Journal of Chemistry,2013,vol. 25,p. 8701 - 8707

42
[ 1558079-66-5 ]
[ 23981-80-8 ]
[ 151213-40-0 ]

Reference： [1]Asian Journal of Chemistry,2013,vol. 25,p. 8701 - 8707

43
[ 23981-80-8 ]
[ 2567-29-5 ]
(±)-3-(biphenyl-4-yl)-2-(6-methoxynaphthalen-2-yl)-2-methylpropanoic acid [ No CAS ]

Reference： [1]Archiv der Pharmazie,2015,vol. 348,p. 55 - 61

44
[ 23981-80-8 ]
[ 508-02-1 ]
oleanoyl naproxenate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With dmap; dicyclohexyl-carbodiimide; In chloroform; at 0 - 20℃;	General procedure: Oleanolic acid (1) or oleanolic acid methyl ester (2) (1 mmol), DCC (1.03 g, 5 mmol), DMAP (0.37 g,3 mmol) and anti-inflammatory drugs: ibuprofen, aspirin, <strong>[23981-80-8]naproxen</strong>, or ketoprofen (4 mmol) weremixed at 0 C and then stirred at room temperature in dry CHCl3 (12 mL) for 2 h. Hexane (8 mL)was added to the reaction mixture and cooled. Next, the resulting precipitate of dicyclohexylureawas filtered. The organic phase was washed with 5% aqueous hydrochloric acid, 5% aqueous sodiumbicarbonate and water and dried over anhydrous sodium sulfate. After removal of the drying agentand solvent evaporation, the crude new esters (11-18) were purified with column chromatography onsilica gel using a hexane-ethyl acetate (4:1, v/v) mixture as an eluent.

Reference： [1]Molecules,2016,vol. 21

45
[ 23981-80-8 ]
[ 1724-17-0 ]
oleanoyl naproxenate methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With dmap; dicyclohexyl-carbodiimide; In chloroform; at 0 - 20℃;	General procedure: Oleanolic acid (1) or oleanolic acid methyl ester (2) (1 mmol), DCC (1.03 g, 5 mmol), DMAP (0.37 g,3 mmol) and anti-inflammatory drugs: ibuprofen, aspirin, <strong>[23981-80-8]naproxen</strong>, or ketoprofen (4 mmol) weremixed at 0 C and then stirred at room temperature in dry CHCl3 (12 mL) for 2 h. Hexane (8 mL)was added to the reaction mixture and cooled. Next, the resulting precipitate of dicyclohexylureawas filtered. The organic phase was washed with 5% aqueous hydrochloric acid, 5% aqueous sodiumbicarbonate and water and dried over anhydrous sodium sulfate. After removal of the drying agentand solvent evaporation, the crude new esters (11-18) were purified with column chromatography onsilica gel using a hexane-ethyl acetate (4:1, v/v) mixture as an eluent.

Reference： [1]Molecules,2016,vol. 21

46
[ 23981-80-8 ]
[ 49815-49-8 ]
oleanoyl oxime naproxenate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With dicyclohexyl-carbodiimide; In chloroform; at 0 - 20℃; for 2h;	General procedure: Oleanolic acid oxime (5) or its methyl ester (6) (1 mmol), DCC (1.03 g, 5 mmol) andanti-inflammatory drugs: ibuprofen, aspirin, <strong>[23981-80-8]naproxen</strong>, or ketoprofen (4 mmol), were mixed at 0 Cand then stirred at room temperature in dry CHCl3 (12 mL) for 2 h. Hexane (8 mL) was added tothe reaction mixture and cooled. Next, the resulting precipitate of dicyclohexylurea was filtered. Theorganic phase was washed with 5% aqueous hydrochloric acid, 5% aqueous sodium bicarbonateand water and dried over anhydrous sodium sulfate. After removal of the drying agent and solventevaporation, the crude new iminoesters 19-26 were purified with column chromatography on silicagel using hexane-ethyl acetate (4:1, v/v) mixture as a eluent.

Reference： [1]Molecules,2016,vol. 21

47
[ 23981-80-8 ]
[ 35137-30-5 ]
oleanoyl oxime naproxenate methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With dicyclohexyl-carbodiimide; In chloroform; at 0 - 20℃; for 2h;	General procedure: Oleanolic acid oxime (5) or its methyl ester (6) (1 mmol), DCC (1.03 g, 5 mmol) andanti-inflammatory drugs: ibuprofen, aspirin, <strong>[23981-80-8]naproxen</strong>, or ketoprofen (4 mmol), were mixed at 0 Cand then stirred at room temperature in dry CHCl3 (12 mL) for 2 h. Hexane (8 mL) was added tothe reaction mixture and cooled. Next, the resulting precipitate of dicyclohexylurea was filtered. Theorganic phase was washed with 5% aqueous hydrochloric acid, 5% aqueous sodium bicarbonateand water and dried over anhydrous sodium sulfate. After removal of the drying agent and solventevaporation, the crude new iminoesters 19-26 were purified with column chromatography on silicagel using hexane-ethyl acetate (4:1, v/v) mixture as a eluent.

Reference： [1]Molecules,2016,vol. 21

48
[ 42088-91-5 ]
[ 23981-80-8 ]
C₂₁H₂₂N₂O₂ [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2016,vol. 14,p. 5511 - 5515

49
[ 42088-91-5 ]
[ 23981-80-8 ]
C₂₉H₂₈N₂O₄ [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2016,vol. 14,p. 5511 - 5515

50
[ 23981-80-8 ]
[ 22204-53-1 ]
[ 23979-41-1 ]
[ 81623-44-1 ]

Reference： [1]Tetrahedron Asymmetry,2017,vol. 28,p. 433 - 441

51
[ 64-18-6 ]
[ 63444-51-9 ]
[ 23981-80-8 ]

Reference： [1]Organic Letters,2017,vol. 19,p. 1748 - 1751

52
[ 23981-80-8 ]
(S)-4-(3-minopiperidin-1-yl)coumarin [ No CAS ]
C₂₈H₂₈N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With dicyclohexyl-carbodiimide; In dichloromethane; at 20℃; for 0.5h;	General procedure: Method A: CDA (1, 4, or 7) and carboxylic acid dissolved in DCM were stirred for 15 min at roomtemperature. N,N?-Dicyclohexylcarbodiimide (DCC) was then added, and the mixture was stirred for 30min at room temperature

Reference： [1]Heterocycles,2017,vol. 94,p. 964 - 978

53
[ 23981-80-8 ]
(S)-4-(3-aminoazepan-1-yl)coumarin [ No CAS ]
C₂₉H₃₀N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With dicyclohexyl-carbodiimide; In dichloromethane; at 20℃; for 0.5h;	General procedure: Method A: CDA (1, 4, or 7) and carboxylic acid dissolved in DCM were stirred for 15 min at roomtemperature. N,N?-Dicyclohexylcarbodiimide (DCC) was then added, and the mixture was stirred for 30min at room temperature

Reference： [1]Heterocycles,2017,vol. 94,p. 964 - 978

54
[ 23981-80-8 ]
(S)-4-(3-aminopyrrolidin-1-yl)coumarin [ No CAS ]
C₂₇H₂₆N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 0.5h;	General procedure: Method C: CDA and carboxylic acid dissolved in DCM were stirred for 10 min at room temperature.EDC was added, and the mixture was stirred for 30 min at room temperature.Then, additional DCM was added, and the solution was washed with 10% aq. HCl, saturated aq. Na2CO3,and brine, and then dried over anhydrous MgSO4, and the solvent was removed in vacuo. The crudeproduct was purified by silica gel preparative thin layer chromatography eluting with EtOAc to give thedesired product

Reference： [1]Heterocycles,2017,vol. 94,p. 964 - 978

55
[ 528-43-8 ]
[ 23981-80-8 ]
C₃₂H₃₀O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With dmap; In dichloromethane; at 25 - 30℃;	General procedure: 1 mmol of magnolol and 1.0 mmol to 2.0 mmol of <strong>[23981-80-8]naproxen</strong> were placed in a round bottom flask and 50 mL of dichloromethane and 0.01 mmol of DMAP (N, N-4-dimethylaminopyridine) A solution of 2 to 3 mmol of EDCI (1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride) or DCC (dicyclohexylcarbodiimide) in dichloromethane was slowly added dropwise at room temperature (25 ~ 30 ) under stirring for 1 ~ 4h, the product by column chromatography separation and purification.Column chromatography separation and purification of the eluent ethyl acetate: petroleum ether = 1:10 ~ 1: 2, spin dry solvent,Dried in vacuo to give a white oily liquid,I.e., compound 5 and compound 6.The yields were 97% and 70%, respectively

Reference： [1]Patent: CN105884614,2016,A .Location in patent: Paragraph 0035-0037

56
[ 528-43-8 ]
[ 23981-80-8 ]
C₄₆H₄₂O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With dmap; In dichloromethane; at 25 - 30℃;	General procedure: 1 mmol of magnolol and 1.0 mmol to 2.0 mmol of naproxen were placed in a round bottom flask and 50 mL of dichloromethane and 0.01 mmol of DMAP (N, N-4-dimethylaminopyridine) A solution of 2 to 3 mmol of EDCI (1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride) or DCC (dicyclohexylcarbodiimide) in dichloromethane was slowly added dropwise at room temperature (25 ~ 30 ) under stirring for 1 ~ 4h, the product by column chromatography separation and purification.Column chromatography separation and purification of the eluent ethyl acetate: petroleum ether = 1:10 ~ 1: 2, spin dry solvent,Dried in vacuo to give a white oily liquid,I.e., compound 5 and compound 6.The yields were 97% and 70%, respectively

Reference： [1]Patent: CN105884614,2016,A .Location in patent: Paragraph 0035-0037

57
[ 124-38-9 ]
[ 63444-51-9 ]
[ 23981-80-8 ]

Reference： [1]Journal of the American Chemical Society,2017,vol. 139,p. 12161 - 12164

58
[ 23981-47-7 ]
[ 23981-80-8 ]

Reference： [1]Organic Letters,2019,vol. 21,p. 3299 - 3303

59
[ 23981-80-8 ]
[ 3900-45-6 ]

Yield	Reaction Conditions	Operation in experiment
72%	With (4s,6s)-2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile; N,N,N',N'-tetramethylguanidine; In acetonitrile; at 20℃; for 6h;Irradiation;	General procedure: To a 25 mL reaction tube, arylacetic acid (0.2 mmol), 4CzIPN (1 mol%), TMG (50 mol%) were dissolved in CH3CN (1.5 mL), and then the tube was stirred in air at room temperature for 6 h with the irradiation of 25 W blue LEDs. After reaction, the mixture was collected, and the residue was purified by column chromatography on silica gel to afford the desired products.

Reference： [1]Chinese Chemical Letters,2019
[2]Green Chemistry,2019,vol. 21,p. 1907 - 1911

60
[ 23981-80-8 ]
[ 700-63-0 ]
C₁₄H₁₄O₃*C₈H₁₀N₂O [ No CAS ]
C₁₄H₁₄O₃*C₈H₁₀N₂O [ No CAS ]

Reference： [1]Crystal Growth and Design,2019,vol. 19,p. 3652 - 3659

61
[ 23981-80-8 ]
[ 81787-62-4 ]
2-[(trimethylsilyl)ethynyl]phenyl 2-(6-methoxynaphthalen-2-yl)propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With dmap; dicyclohexyl-carbodiimide In dichloromethane for 2.5h; Inert atmosphere;

Reference： [1]Fernández-Canelas, Paula; Rubio, Eduardo; González, José M. [Organic Letters, 2019, vol. 21, # 16, p. 6566 - 6569]

62
[ 21388-17-0 ]
[ 124-38-9 ]
[ 23981-80-8 ]

Reference： [1]Journal of the American Chemical Society,2019,vol. 141,p. 11393 - 11397

63
[ 23981-80-8 ]
2-(5,5-difluoro-6-oxo-5,6-dihydronaphthalen-2-yl)propionic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With Selectfluor; In water; acetonitrile; at 20℃; for 23h;	A mixture of <strong>[23981-80-8]naproxen</strong> (200 mg, 0.87 mmol), F-TEDA-BF4 (680 mg, 1.92 mmol), CH3CN (26.6 mL) and water (1.4 mL) was stirred at room temperature for 23 h. Then the solvents were removed under reduced pressure. The yellow solid obtained was shaken with ether (50 mL), filtrated, the organic solution was evaporated under reduced pressure. The yellow-brown oil obtained gradually solidified. Yellow-brownish solid, yield - 0.192 g (87 %). The crystals of compound 3 suitable for X-ray analysis were obtained by recrystallization from n-hexane-CHCl3. White needles, mp 88-90 C. FT-IR (CHCl3): 1703 (two overlapping signals of C=O groups), 1603, 1576, 1458 cm-1. 1H NMR (300 MHz, CDCl3): 11.20 (br s, 1H, COOH), 7.77 (d, J = 8 Hz, 1H), 7.46 (dd, J = 8, 1.3 Hz, 1H), 7.40 (d, J = 10.1 Hz, 1H), 7.32 (d, J = 0.8 Hz), 6.22 (dt, J = 10.1, 2.7 Hz, 1H), 3.80 (q, J = 7.2 Hz, 1H), 1.55 (d, J = 7.2 Hz, 3H, CH3). 13C NMR (125 MHz, CDCl3): 187.2 (t, J = 24.8 Hz, C6'=O), 179.3 (C=O), 145.2, 143.9, 132.2 (t, J = 23.7 Hz), 130.6 (t, J = 5.7 Hz), 130.1, 129.1, 128.0 (t, J = 3 Hz), 123.8, 105.3 (t, 1JCF = 245 Hz, C-5'), 44.9 (C-2), 17.8 (CH3). 19F NMR (282 MHz, CDCl3): -102.06 (s, 2F, 5'-CF2). HRMS (DFS), m/z: calcd for C13H10O3F2+ 252.0593; found 252.0592.

Reference： [1]Journal of Fluorine Chemistry,2019,vol. 228
[2]Journal of Fluorine Chemistry,2019,vol. 228

64
[ 23981-80-8 ]
[ 15965-30-7 ]
4,5-dichloro-1-(1-(6-methoxynaphthalen-2-yl)ethyl)-1H-imidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With tris-(4,4’-di-tert-butyl-2,2’-bipyridine)ruthenium(II) hexafluorophosphate; 3-oxo-2-tosyl-2,3-dihydro-1H-1λ³-benzo[d][1,2]iodazol-1-yl acetate In 1,2-dichloro-ethane at 20℃; for 20h; Sealed tube; Inert atmosphere; Irradiation;

Reference： [1]Li, Peijun; Zbieg, Jason R.; Terrett, Jack A. [Organic Letters, 2021, vol. 23, # 24, p. 9563 - 9568]

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CAS No. :	23981-80-8	MDL No. :	MFCD00439456
Formula :	C₁₄H₁₄O₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	CMWTZPSULFXXJA-UHFFFAOYSA-N
M.W :	230.26	Pubchem ID :	1302
Synonyms :	(Rac)-Naproxen	Chemical Name :	2-(6-Methoxynaphthalen-2-yl)propanoic acid

Num. heavy atoms :	17
Num. arom. heavy atoms :	10
Fraction Csp3 :	0.21
Num. rotatable bonds :	3
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	66.79
TPSA :	46.53 Å²

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

Log Po/w (iLOGP) :	2.06
Log Po/w (XLOGP3) :	3.34
Log Po/w (WLOGP) :	3.04
Log Po/w (MLOGP) :	2.57
Log Po/w (SILICOS-IT) :	2.9
Consensus Log Po/w :	2.78

[ CAS No. 23981-80-8 ] {[proInfo.proName]}

Quality Control of [ 23981-80-8 ]

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[ 23981-80-8 ] Synthesis Path-Upstream 1~2

[ 23981-80-8 ] Synthesis Path-Downstream 1~64

Related Functional Groups of
[ 23981-80-8 ]

Aryls

Ethers

Carboxylic Acids

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

Log S (ESOL) :	-3.61
Solubility :	0.0566 mg/ml ; 0.000246 mol/l
Class :	Soluble
Log S (Ali) :	-3.99
Solubility :	0.0233 mg/ml ; 0.000101 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.02
Solubility :	0.0221 mg/ml ; 0.0000962 mol/l
Class :	Moderately soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.85

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:

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
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P331	Do NOT induce vomiting.
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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
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P413
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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. 23981-80-8 ] {[proInfo.proName]}

Quality Control of [ 23981-80-8 ]

Related Doc. of [ 23981-80-8 ]

Product Details of [ 23981-80-8 ]

Calculated chemistry of [ 23981-80-8 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 23981-80-8 ]

Application In Synthesis of [ 23981-80-8 ]

[ 23981-80-8 ] Synthesis Path-Upstream 1~2

[ 23981-80-8 ] Synthesis Path-Downstream 1~64

Related Functional Groups of [ 23981-80-8 ]

Aryls

Ethers

Carboxylic Acids

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 23981-80-8 ]