Name: 114772-34-8|Methyl 4'-methyl-[1,1'-biphenyl]-2-carboxylate|98%
Brand: Ambeed
SKU: A773072
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1
[ 67-56-1 ]
[ 7148-03-0 ]
[ 114772-34-8 ]

Yield	Reaction Conditions	Operation in experiment
98.05%	With dmap; dicyclohexyl-carbodiimide; at 25℃; for 3h;Large scale;	To the kettle was added 5.30 kg4 & ' -methyl-2-carboxylic acid biphenyl,Anhydrous methanol 10. 60 kg,5. 83 kg DCC,0. 09 kg DMAP,25 C reaction for 3 hours,After filtration, the filtrate into another reactor, adding 50. 00kg of water, stirring crystallization, and then centrifuged, washed to neutral, 40 C vacuum drying 24 hours to get 5. 54kg4 '- methyl -2-- Formate biphenyl,Melting point 55 ~ 57 C, yield 98. 05%, purity 99. 06%.
94%	With sulfuric acid; for 5h;Reflux;	General procedure: 4?-Methyl-[1,1?-biphenyl]-carboxylicacid (0.25 g, 1.18 mmol) was suspended with stirring in10 ml of abs. methanol. Subsequently, 0.13 ml of conc. H2SO4were added and the mixture was heated to reflux for 5h. After cooling to RT, 10ml of water were added and the product was extracted with methylene chloride.The combined organic layers dried over sodium sulfate and the solvent wasevaporated in vacuo. The crude product was purified by column chromatography onsilica gel with methylene chloride/methanol (95:5).
13.9 g	With sulfuric acid; for 5h;Reflux;	A 250 ml four-necked flask was charged with 20.3 g of 4?-methylbiphenyl-2-carboxylic acid methyl ester residue (main content: 73%), 12.0 g of sodium hydroxide, and 58.1 g of drinking water, and heated to 80 C. for 10 hours for hydrolysis. The remaining 4'-methyl biphenyl-2-carboxylic acid methyl ester was detected by HPLC by 0.31%; the temperature was lowered to below 30 C, 40.5 g of dichloromethane was added, stirred for 30 minutes, and left for 30 minutes. The lower solvent layer was separated, and the upper water layer was added. 41.0 g of methylene chloride, 39.2 g of 31% hydrochloric acid was added dropwise with stirring, and the pH was adjusted to 1.Continue to stir for 30min, and let stand for 30min. Separate the lower dichloromethane layer (HPLC detected 4?-methylbiphenyl-2-carboxylic acid content is 98.8%) and evaporate to dryness, then add 11.0g of methanol and continue to evaporate to dryness; evaporate to dryness After that, 30.7 g of methanol and 10.0 g of sulfuric acid were added, and the reaction was stirred at reflux for 5 hours. The content of methyl 4?-methylbiphenyl-2-carboxylic acid was 98.3% by HPLC, and the temperature was lowered to 0-5 C., followed by crystallization with stirring for 1 hour. , 13.9 g of dry product 4?-methylbiphenyl-2-carboxylic acid methyl ester was obtained by suction filtration, and the content of HPLC was 99.6%.

Reference： [1]Patent: CN105399627,2016,A .Location in patent: Paragraph 0056; 0057
[2]European Journal of Medicinal Chemistry,2016,vol. 124,p. 138 - 152
[3]Journal of Medicinal Chemistry,1991,vol. 34,p. 2525 - 2547
[4]Patent: CN110372511,2019,A .Location in patent: Paragraph 0022-0033

2
[ 624-31-7 ]
[ 610-97-9 ]
[ 114772-34-8 ]

Yield	Reaction Conditions	Operation in experiment
11%	With copper at 210℃; for 1h;
	With bis-triphenylphosphine-palladium(II) chloride; tributyltin chloride; iodine; magnesium; lithium chloride 1.) THF, reflux, 30 min; THF, reflux, 20 h, 2.) DMF, 98 deg C, 24 h; Yield given. Multistep reaction;

Reference： [1]Carini, David J.; Duncia, John V.; Aldrich, Paul E.; Chiu, Andrew T.; Johnson, Alexander L.; et al. [Journal of Medicinal Chemistry, 1991, vol. 34, # 8, p. 2525 - 2547]
[2]Delgado; Pastor; Garcia-Navio; Vaquero; Alvarez-Builla; Sunkel; De Casa-Juana; Priego; Santos; Statkow; Straumann [Il Farmaco, 1997, vol. 52, # 3, p. 147 - 155]

3
[ 114772-34-8 ]
[ 7148-03-0 ]

Yield	Reaction Conditions	Operation in experiment
510 g (100%)	With sodium hydroxide; In ethanol;	Step 3: Preparation of N-triphenylmethyl-5-[2-(4'-bromomethylbiphen-2-yl]tetrazole. A 542.5 g (2.4 mol) sample of methyl 2-(p-tolyl) benzoate (Chemo Dynamics Inc.) was dissolved in 5.5 L of ethanol and treated with 3 L (7.5 mol) of 2.5 N sodium hydroxide. The reaction was stirred overnight at ambient temperature and treated with an additional 480 mL (6.0 mol) of sodium hydroxide; stirring was continued for an additional 24 h and the ethanol removed in vacuo. The remaining solution was cooled in ice and acidified to pH 1 with hydrochloric acid which caused the product to precipitate; filtration and drying in vacuo gave 510 g (100%) of crude 2-(p-tolyl)benzoic acid: mp 145.0-147.5 C.; NMR (CDCl3) delta 2.40 (s, 3H), 7.17-7.28 (m, 4H), 7.35-7.45 (m, 2H), 7.51-7.59 (m, 1H), 7.90-7.97 (m, 1H).
510 g (100%)	With sodium hydroxide; In ethanol;	Step 1: Preparation of N-Triphenylmethyl-5-[2-(4'-bromomethylbiphen -2-yl]tetrazole. A 542.5 g (2.4 mol) sample of methyl 2-(p-tolyl)benzoate (Chemo Dynamics Inc.) was dissolved in 5.5 L of ethanol and treated with 3 L (7.5 mol) of 2.5 N sodium hydroxide. The reaction was stirred overnight at ambient temperature and treated with an additional 480 ml (6.0 mol) of sodium hydroxide; stirring was continued for an additional 24 h and the ethanol removed in vacuo. The remaining solution was cooled in ice and acidified to pH 1 with hydrochloric acid which caused the product to precipitate; filtration and drying in vacuo gave 510 g (100%) of crude 2-(p-tolyl)benzoic acid: mp 145.0-147.5 C.; NMR (CDCl3) delta2.40 (s, 3H), 7.17-7.28 (m, 4H), 7.35-7.45 (m, 2H), 7.51-7.59 (m, 1H), 7.90-7.97 (m, 1H).
	With potassium hydroxide; In methanol; water; ethyl acetate;	Step A Preparation of 4'-methylbiphenyl-2-carboxylic acid Methyl 4'-methylbiphenyl-2-carboxylate (10.0 g, 44.2 mmol, 1 eq), 0.5 N KOH in methanol (265.5 mL, 133 mmol, 3 eq), and water (50 mL) were mixed and refluxed under N2. After 5 hours, the solvent was removed in vacuo and water (200 mL) and ethyl acetate (200 mL) added. The aqueous layer was acidified with concentrated hydrochloric acid to a pH of 3 and the layers were separated. The aqueous phase was extracted with ethyl acetate (2*200 mL), the organic layers collected, dried (MgSO4) and the solvent removed in vacuo to yield 8.71 g of a white solid; m.p. 140.0-145.0. NMR (200 MHz, DMSO-d6) delta 7.72 (d, 1H, J=7 Hz); 7.56 (t, 1H, J=7 Hz); 7.45 (d, 1H, J=7 Hz); 7.40 (t, 1H, J=7 Hz); 7.25 (s, 4H); 2.36 (s, 3H). Anal Calcd. for C14 H12 O2; C, 79.23; H, 5.70. Found: C, 79.22; H, 5.47.

510 g (100%)	With sodium hydroxide; In ethanol;	Step 1: Preparation of N-Triphenylmethyl-5-2-(4'-bromomethylbipen-2-yl]tetrazole A 542.5 g (2.4 mol) sample of methyl 2-(p-tolyl)benzoate (Chemo Dynamics Inc.) was dissolved in 5.5 L of ethanol and treated with 3 L (7.5 mol) of 2.5N sodium hydroxide. The reaction was stirred overnight at ambient temperature and treated with an additional 480 ml (6.0 mol) of sodium hydroxide; stirring was continued for an additional 24 h and the ethanol removed in vacuo. The remaining solution was cooled in ice and acidified to pH 1 with hydrochloric acid which caused the product to precipitate; filtration and drying in vacuo gave 510 g (100%) of crude 2-(p-tolyl)benzoic acid: mp 145.0-147.5 C.; NMR (CDCl3) delta2.40 (s, 3H), 7.17-7.28 (m, 4H), 7.35-7.45 (m, 2H), 7.51-7.59 (m, 1H), 7.90-7.97 (m, 1H).
	With potassium hydroxide; In methanol; water; ethyl acetate;	Step A Preparation 4'- methylbiphenyl-2-carboxylic acid Methyl 4'-methylbiphenyl-2-carboxylate (10.0 g, 44.2 mmol, 1 eq), 0.5N KOH in methanol (265.5 mL, 133 mmol, 3 eq), and water (50 mL) were mixed and refluxed under N2. After 5 hours, the solvent was removed in vacuo and water (200 mL) and ethyl acetate (200 mL) added. The aqueous layer was acidified with concentrated hydrochloric acid to a pH of 3 and the layers were separated. The aqueous phase was extracted with ethyl acetate (2*200 mL), the organic layers collected, dried (MgSO4) and the solvent removed in vacuo to yield 8.71 g of a white solid; m.p. 140.0-145.0. NMR (200 MHz, DMSO-d6)delta7.72 (d, 1H, J=7 Hz); 7.56 (t, 1H, J=7 Hz); 7.45 (d, 1H, J=7 Hz); 7.40 (t, 1H, J=7 Hz); 7.25 (s, 4H); 2.36 (s, 3H). Anal Calcd. for C14 H12 O2; C, 79.23; H, 5.70. Found: C, 79.22; H, 5.47.
510 g (100%)	With sodium hydroxide; In ethanol;	Step 1 Preparation of N-Triphenylmethyl-5-[2-(4'-bromomethylbiphen-2-yl]tetrazole A 542.5 g (2.4 mol) sample of methyl 2-(p-tolyl)benzoate (Chemo Dynamics Inc.) was dissolved in 5.5 L of ethanol and treated with 3 L (7.5 mol) of 2.5 N sodium hydroxide. The reaction was stirred overnight at ambient temperature and treated with an additional 480 ml (6.0 mol) of sodium hydroxide; stirring was continued for an additional 24 h and the ethanol removed in vacuo. The remaining solution was cooled in ice and acidified to pH 1 with hydrochloric acid which caused the product to precipitate; filtration and drying in vacuo gave 510 g (100%) of crude 2-(p-tolyl)benzoic acid: mp 145.0-147.5 C.; NMR (CDCl3) delta 2.40 (s, 3H), 7.17-7.28 (m, 4H), 7.35-7.45 (m, 2H), 7.51-7.59 (m, 1H), 7.90-7.97 (m, 1H).
	With potassium hydroxide; In methanol; water; ethyl acetate;	Part A Preparation of 4'-methylbiphenyl-2-carboxylic acid Methyl 4'-methylbiphenyl-2-carboxylate (10.0 g, 44.2 mmol, 1 eq), 0.5N KOH in methanol (265.5 mL, 133 mmol, 3 eq), and water (50 mL) were mixed and refluxed under N2. After 5 hours, the solvent was removed in vacuo and water (200 mL) and ethyl acetate (200 mL) added. The aqueous layer was acidified with concentrated hydrochloric acid to a pH of 3 and the layers were separated. The aqueous phase was extracted with ethyl acetate (2*200 mL), the organic layers collected, dried (MgSO4) and the solvent removed in vacuo to yield 8.71 g of a white solid; m.p. 140.0-145.0. NMR (200 MHz, DMSO-d6) delta7.72 (d, 1H, J=7 Hz); 7.56 (t, 1H, J=7 Hz); 7.45 (d, 1H, J=7 Hz); 7.40 (t, 1H, J=7 Hz); 7.25 (s, 4H); 2.36 (s, 3H). Anal. Calcd. for C14 H12 O2; C, 79.23; H, 5.70. Found: C, 79.22; H, 5.47.
510 g (100%)	With sodium hydroxide; In ethanol;	Step 1: Preparation of N-Triphenylmethyl-5-[2-(4'-bromemethylbiphen-2-yl]tetrazole A 542 5 g (2.4 mol) sample of methyl 2-(p-tolyl)benzoate (Chemo Dynamics Inc.) was dissolved in 5.5 L of ethanol and treated with 3 L (7.5 mol) of 2.5 N sodium hydroxide. The reaction was stirred overnight at ambient temperature and treated with an additional 480 ml (6.0 mol) of sodium hydroxide; stirring was continued for an additional 24 h and the ethanol removed in vacuo. The remaining solution was cooled in ice and acidified to pH 1 with hydrochloric acid which caused the product to precipitate; filtration and drying in vacuo gave 510 g (100%) of crude 2-(p-tolyl)benzoic acid: mp 145.0-147.5 C.; NMR (CDCl3) delta 2.40 (s, 3H), 7.17-7.28 (m, 4H), 7.35-7.45 (m, 2H), 7.51-7.59 (m, 1H), 7.90-7.97 (m, 1H).
	With potassium hydroxide; In methanol; water; ethyl acetate;	Step A Preparation of 4'-methylbiphenyl-2-carboxylic acid Methyl 4'-methylbiphenyl-2-carboxylate (10.0 g, 44.2 mmol, 1 eq), 0.5N KOH in methanol (265.5 mL, 133 mmol, 3 eq), and water (50 mL) were mixed and refluxed under N2. After 5 hours, the solvent was removed in vacuo and water (200 mL) and ethyl acetate (200 mL) added. The aqueous layer was acidified with concentrated hydrochloric acid to a pH of 3 and the layers were separated. The aqueous phase was extracted with ethyl acetate (2*200 mL), the organic layers collected, dried (MgSO4) and the solvent removed in vacuo to yield 8.71 g of a white solid; m.p. 140.0-145.0. NMR (200 MHz, DMSO-d6) delta 7.72 (d, 1H, J=7Hz); 7.56 (t, 1H, J=7 Hz); 7.45 (d, 1H, J=7 Hz); 7.40 (t, 1H, J=7 Hz); 7.25 (s, 4H); 2.36 (s, 3H). Anal Calcd. for C14 H12 O2; C, 79.23; H, 5.70. Found: C, 79.22; H, 5.47.
	With potassium hydroxide; In methanol; water; ethyl acetate;	Part A: Preparation of 4'-methylbiphenyl-2-carboxylic acid Methyl 4'-methylbiphenyl-2-carboxylate (10.0 g, 44.2 mmol, 1 eq), 0.5N KOH in methanol (265.5 mL, 133 mmol, 3 eq), and water (50 mL) were mixed and refluxed under N2. After 5 hours, the solvent was removed in vacuo and water (200 mL) and ethyl acetate (200 mL) added. The aqueous layer was acidified with concentrated hydrochloric acid to a pH of 3 and the layers were separated. The aqueous phase was extracted with ethyl acetate (2*200 mL), the organic layers collected, dried (MgSO4) and the solvent removed in vacuo to yield 8.71 g of a white solid; m.p. 140.0-145.0. NMR (200 MHz, DMSO-d6) delta 7.72 (d, 1H, J=7Hz); 7.56 (t, 1H, J=7Hz); 7.45 (d, 1H, J=7Hz); 7.40 (t, 1H, J=7Hz); 7.25 (s, 4H); 2.36 (s, 3H). Anal. Calcd. for C14 H12 O2; C, 79.23; H, 5.70. Found: C, 79.22; H, 5.47.
	With water; sodium hydroxide; at 80℃; for 10h;	A 250 ml four-necked flask was charged with 20.3 g of 4?-methylbiphenyl-2-carboxylic acid methyl ester residue (main content: 73%), 12.0 g of sodium hydroxide, and 58.1 g of drinking water, and heated to 80 C. for 10 hours for hydrolysis. The remaining 4'-methyl biphenyl-2-carboxylic acid methyl ester was detected by HPLC by 0.31%; the temperature was lowered to below 30 C, 40.5 g of dichloromethane was added, stirred for 30 minutes, and left for 30 minutes. The lower solvent layer was separated, and the upper water layer was added. 41.0 g of methylene chloride, 39.2 g of 31% hydrochloric acid was added dropwise with stirring, and the pH was adjusted to 1.Continue to stir for 30min, and let stand for 30min. Separate the lower dichloromethane layer (HPLC detected 4?-methylbiphenyl-2-carboxylic acid content is 98.8%) and evaporate to dryness, then add 11.0g of methanol and continue to evaporate to dryness; evaporate to dryness After that, 30.7 g of methanol and 10.0 g of sulfuric acid were added, and the reaction was stirred at reflux for 5 hours. The content of methyl 4?-methylbiphenyl-2-carboxylic acid was 98.3% by HPLC, and the temperature was lowered to 0-5 C., followed by crystallization with stirring for 1 hour. , 13.9 g of dry product 4?-methylbiphenyl-2-carboxylic acid methyl ester was obtained by suction filtration, and the content of HPLC was 99.6%.

Reference： [1]Journal of Medicinal Chemistry,1993,vol. 36,p. 2172 - 2181
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[5]Bioorganic and Medicinal Chemistry,2006,vol. 14,p. 4490 - 4518
[6]Patent: US2001/20100,2001,A1
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[13]Patent: US5098920,1992,A
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[19]Patent: US5128355,1992,A
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[21]Patent: CN110372511,2019,A .Location in patent: Paragraph 0022-0033
[22]Organic Letters,2020,vol. 22,p. 4129 - 4134

4
[ 114772-34-8 ]
[ 114772-78-0 ]

Yield	Reaction Conditions	Operation in experiment
42.55 g	With diisobutylaluminium hydride In toluene at -78 - -70℃; for 0.25h;

Reference： [1]Carini, David J.; Duncia, John V.; Aldrich, Paul E.; Chiu, Andrew T.; Johnson, Alexander L.; et al. [Journal of Medicinal Chemistry, 1991, vol. 34, # 8, p. 2525 - 2547]

5
[ 114772-34-8 ]
[ 114772-38-2 ]

Yield	Reaction Conditions	Operation in experiment
90%	With N-Bromosuccinimide; In dichloromethane; at 25℃; for 5h;Irradiation; Large scale;	To the reactor were added5. 54 kg of 4'-methyl-2-formate biphenyl, methylene chloride 27. 70 kg, 4.80 kg NBS,Under the condition of 180001chi light,25 C for 5 hours. The reaction solution was gradually changed from brownish red to pale yellow, washed with 20% aqueous sodium bisulfite solution (20.00 kg) and saturated brine (20.00 g) and water (20.00%), and finally dried over anhydrous sodium sulfate The organic layer was filtered, filtered and dried at 50 C to concentrate methylene chloride to dryness, then 5.50 kg of methanol,Quickly cooled to 0 C stirring crystallization for 5 hours, filtration.The mixture was vacuum dried at 35 C for 8 hours to obtain 6. 72 kg of 4 '-bromomethylbiphenyl-2-carboxylate in a yield of about 90% and a purity of 99.13%
83%	With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 4h;Reflux;	General procedure: 4'-Methyl-[1,1'-biphenyl]-carboxylate (0.15 g, 0.66 mmol)was dissolved in 10 ml of carbon tetrachloride. N-Bromosuccinimide (0.13 g, 0.73 mmol) and benzoyl peroxide (9 mg, 0.04 mmol)were added with stirring. The mixture was heated to reflux for 4 h andfiltered. The solvent was evaporated in vacuo. The crude product waspurified by column chromatography on silica gel with petrol ether/diethyl ether(5:1).
50.0 g (78%)	With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); azobisisobutyronitrile; In tetrachloromethane;	Step 1: Preparation of 4-bromomethyl-2'-methoxycarbonylbiphenyl A 47.46 g (210 mmol) sample of methyl 2-(p-tolyl)benzoate (Chemo Dynamics Inc.) was dissolved in 3L of carbon tetrachloride and treated with 37.33 g (209 mmol) of N-bromosuccinimide (NBS) and 1.17 g (7.13 mmol) of azobisisobutyronitrile (AIBN) at reflux under nitrogen for 24 hours. The reaction mixture was treated again with 1.0 g (6.1 mmol) of AIBN and stirred at reflux for an additional 24 hours. The reaction was filtered and the solvent removed in in vacuo. Purification by silica gel chromatography (Waters Prep-500A) using ethyl acetate/hexane (5:95) as eluent provided 50.0 g (78%) of a colorless solid: mp 48-51 C.; NMR (CDCl3) delta3.64 (s, 3H), 4.54 (s, 2H), 7.23-7.63 (m, 7H), 7.81-7.89 (m, 1H). NMR indicated that this material was only 91% pure; it contained 9% of the corresponding dibromocompound (delta6.70); however, no further attempts at purification were made and this mixture was used in all subsequent alkylation reactions.

50.0 g (78%)	With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); azobisisobutyronitrile; In tetrachloromethane;	Step 1: Preparation of 4-bromomethyl-2'-methoxycarbonylbiphenyl A 47.46 g (210 mmol) sample of methyl 2-(p-tolyl)benzoate (Chemo Dynamics Inc.) was dissolved in 3 L of carbon tetrachloride and treated with 37.33 g (209 mmol) of N-bromosuccinimide (NBS) and 1.17 g (7.13 mmol) of azobisisobutyronitrile (AIBN) at reflux under nitrogen for 24 hours. The reaction mixture was treated again with 1.0 g (6.1 mmol) of AIBN and stirred at reflux for an additional 24 hours. The reaction was filtered and the solvent removed in in vacuo. Purification by silica gel chromatography (Waters Prep-500A) using ethyl acetate/hexane (5:95) as eluent provided 50.0 g (78%) of a colorless solid: mp 48-51 C.; NMR (CDCl3) delta 3.64 (s, 3H), 4.54 (s, 2H), 7.23-7.63 (m, 7H), 7.81-7.89 (m, 1H). NMR indicated that this material was only 91% pure; it contained 9% of the corresponding dibromocompound (delta 6.70); however, no further attempts at purification were made and this mixture was used in all subsequent alkylation reactions.
	With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; at 80℃; for 6h;	[0189] A mixture of the carboxylate (1.92 g, 8.50 mmol), N-bromosuccinimide (1.67 g, 9.37 mmol), and 2,2'-azobisisobutyronitrile (0.039, 0.24 mmol) was suspended in 80 mL carbon tetrachloride, and heated at 80 C. for 6 hours. The mixture was filtered, the solvent was evaporated at reduced pressure, and the residue was dissolved in ethyl acetate and washed with NaHCO3, H2O, saturated NaCl, and dried over MgSO4. The solvent was evaporated and residue was purified on a silica gel column eluted with 10% ethyl acetate in hexanes to afford 1.70 g of methyl 4'-(bromomethyl)biphenyl-2-carboxylate as an oil with a mass ion (ES+) of 305.0 for M+H+.
	With N-Bromosuccinimide;2,2'-azobis(isobutyronitrile); In tetrachloromethane; for 6h;Heating / reflux;	EXAMPLE 1 Method A Methyl 4'-[({3-[(3-cyanopropanoyl)amino]pyridin-2-yl}amino)methyl]-1,1'-biphenyl-2-carboxylate: [0185] [CHEMMOL-00015] [0186] A solution of 4'-methyl-2-biphenylcarboxylic acid (2.0 g, 9.43 mmol) in 25 mL of methanol was treated with trimethylsilyldiazomethane (7.5 ml of a 2.0 M solution in hexane, 15 mmol). The resulting mixture was stirred for 4 hr at rt. The solvent was evaporated at reduced pressure and the residue was dissolved in CH2Cl2 and washed with NaHCO3, H2O, saturated NaCl, and dried over MgSO4. The solvent was evaporated to give crude 1.92 g (97%) methyl 4'-methyl-biphenyl-2-carboxylate as a white solid with a mass ion (ES+) of 227.1 for M+H+. A mixture of the carboxylate (1.92 g, 8.50 mmol), N-bromosuccinimide (1.67 g, 9.37 mmol), and 2,2'-azobisisobutyronitrile (0.039, 0.24 mmol) was suspended in 80 mL carbon tetrachloride, and heated to reflux for 6 hours. The reaction mixture was filtered, concentrated, and the residue was dissolved in ethyl acetate and washed with NaHCO3, H2O, saturated NaCl, and dried over MgSO4. The solvent was evaporated and residue was eluted with 10% ethyl acetate in hexanes on a silica gel column to afford 1.70 g of methyl 4'-(bromomethyl)biphenyl-2-carboxylate as a yellow oil with a mass ion (ES+) of 305.0 for M+H+. [0187] To a stirred solution of 2-amino-3-nitropyridine (0.278 g, 2.0 mmol) in DMF (2 mL) at 0 C., sodium hydride (80% dispersion in mineral oil, 0.066 g, 2.1 mmol) was added, and stirred at 0 C. for 30 minutes. A solution of methyl 4'-(bromomethyl)biphenyl-2-carboxylate (0.610 g, 2 mmol) in DMF (0.5 ml) was added, and stirring continued at 0 C. for another 2 hr. The reaction was quenched by saturated NH4Cl and partitioned between ethyl acetate and water. The organic extract was washed with brine, dried over MgSO4, filtered and concentrated under vacuum. The residue was eluted on silica gel with 25% ethyl acetate in hexanes to provide 0.305 g methyl 4'-[(3-nitropyridin-2-yl)amino]methyl}-biphenyl-2-carboxylate as a yellow solid with a mass ion (ES+) of 364.1 for M+H+. [0188] To a solution of the above product (0.676 g, 1.0 mmol) in ethyl acetate (10 mL) and ethanol (190 ml), Raney 2800 nickel (slurry in water) was added and stirred under H2 (balloon) for 1 hr. The black suspension was filtered and the filtrate was concentrated under vacuum. The residue was subjected to silica gel chromatography eluted with 50% ethyl acetate in hexanes to give 0.27 g methyl 4'-[(3-aminopyridin-2-yl)amino]methyl}-biphenyl-2-carboxylate as a yellow solid with a mass ion (ES+) of 334.1 for M+H+. [0189] A solution of beta-CN-propionic methyl ester (226 mg, 2.0 mmol) in MeOH (3 mL), 4 N NaOH (1 ml) and water (4 ml) was stirred 7 hr at rt and neutralized with 6N HCl. The solvent was concentrated under vacuum to give a white residue. The white residue was added to a solution of methyl 4'-[(3-amino-4-pyridin-2-yl)amino)methyl]biphenyl-2-carboxylate (0.167 g, 0.5 mmol) in DMF (1 ml), and 1-ethyl-(3-dimethylaminopropyl)carbodimide hydrochloride (134 mg, 0.7 mmol), 1-hydroxy-7-azabenzotriazole (68 mg, 0.5 mmol), N,N-diisopropylethylamine was added until pH=9.5. The resulting solution was stirred for 3 hr at rt and the reaction mixture was partitioned between ethyl acetate and water. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under vacuum. Purification was achieved by preparative HPLC with a small amount or trifluoroacetic acid to give the title compound as the trifluoracetic acid salt that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 415.3 for M+H+: 1H NMR (400 MHz, DMSO-d6) delta 2.77 (t, J=7.33 Hz, 2H), 2.84 (t, J=7.44 Hz, 2H), 3.62 (s, 3H), 4.79(s, 2H). 6.89 (br s, 1H), 7.28 (d, J=7.57, 2H), 7.46 (m, 4H), 7.62(dd, J=7.57 Hz, 1H), 7.74 (d, J=7.6 Hz, 1H), 7.82 (d, J=7.2 Hz, 1H), 7.91 (s, 1H), 9.3 (br s, 1H)
	With N-Bromosuccinimide; 2,2'-azobis-(2,4-dimethylvaleronitrile); In tetrachloromethane; for 6h;Heating / reflux;	2, 2-azobisisobutyronitrile(6.91g) and N-bromosuccinimide (302mg) were added to methyl 4'-methlbiphenyl-2-carboxylate(8.78g) in carbon tetrachloride(500mL) solution. The mixture was refluxed for 6 hours under argon gas and filtered after being cooled to room temperature, and then concentrated. The titled compound(9.30g) having the following physical data was obtained by purifying the obtained residue by silica gel column chromatography(ethyl acetate:hexane=1:5). TLC: Rf 0.59 (ethyl acetate:hexane=1:4); NMR (CDCl3): delta 7.89-7.82 (m, 1H), 7.63-7.26 (m, 7H), 4.55 (s, 2H), 3.65 (s, 2H).

Reference： [1]Patent: CN105399627,2016,A .Location in patent: Paragraph 0058; 0059
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[4]European Journal of Medicinal Chemistry,2016,vol. 124,p. 138 - 152
[5]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 2370 - 2378
[6]Journal of Medicinal Chemistry,1991,vol. 34,p. 2525 - 2547
[7]Il Farmaco,1997,vol. 52,p. 147 - 155
[8]Bioorganic and Medicinal Chemistry Letters,2000,vol. 10,p. 2149 - 2152
[9]Journal of Medicinal Chemistry,2001,vol. 44,p. 703 - 714
[10]Patent: US5217985,1993,A
[11]Patent: US5098920,1992,A
[12]Patent: US2004/34064,2004,A1 .Location in patent: Page/Page column 14
[13]Patent: US2004/44041,2004,A1 .Location in patent: Page/Page column 14
[14]Patent: EP1745800,2007,A1 .Location in patent: Page/Page column 35
[15]Journal of Chemical Sciences,2014,vol. 126,p. 205 - 212

6
[ 610-96-8 ]
[ 5720-05-8 ]
[ 114772-34-8 ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium fluoride In toluene at 80℃; for 2h;
83%	With potassium phosphate; triphenylphosphine In toluene at 100℃; for 2h;

Reference： [1]Suzuki, Ken; Fontaine, Arnaud; Hori, Yoji; Kobayashi, Tohru [Synlett, 2007, # 20, p. 3206 - 3208]
[2]Inada, Kaoru; Miyaura, Norio [Tetrahedron, 2000, vol. 56, # 44, p. 8657 - 8660]

7
[ 7148-03-0 ]
[ 18107-18-1 ]
[ 114772-34-8 ]

Yield	Reaction Conditions	Operation in experiment
97%	In methanol; for 4h;	[0188] To a solution of 4'-methyl-2-biphenylcarboxylic acid (2.0 g, 9.43 mmol) in methanol (25 ml) was added trimethylsilyl-diazomethane (7.5 ml, 15 mmole). The resulting mixture was stirred for 4 hours. The solvent was evaporated at reduced pressure and the residue was dissolved in CH2Cl2 and washed with NaHCO3, H2O, saturated NaCl, and dried over MgSO4. The solvent was evaporated to give 1.92 g (97%) of crude methyl 4'-methyl-biphenyl-2-carboxylate as a white solid with a mass ion (ES+) of 227.1 for M+H+.
97%	In methanol; hexane; at 20℃; for 4h;	EXAMPLE 1 Method A Methyl 4'-[({3-[(3-cyanopropanoyl)amino]pyridin-2-yl}amino)methyl]-1,1'-biphenyl-2-carboxylate: [0185] [CHEMMOL-00015] [0186] A solution of 4'-methyl-2-biphenylcarboxylic acid (2.0 g, 9.43 mmol) in 25 mL of methanol was treated with trimethylsilyldiazomethane (7.5 ml of a 2.0 M solution in hexane, 15 mmol). The resulting mixture was stirred for 4 hr at rt. The solvent was evaporated at reduced pressure and the residue was dissolved in CH2Cl2 and washed with NaHCO3, H2O, saturated NaCl, and dried over MgSO4. The solvent was evaporated to give crude 1.92 g (97%) methyl 4'-methyl-biphenyl-2-carboxylate as a white solid with a mass ion (ES+) of 227.1 for M+H+. A mixture of the carboxylate (1.92 g, 8.50 mmol), N-bromosuccinimide (1.67 g, 9.37 mmol), and 2,2'-azobisisobutyronitrile (0.039, 0.24 mmol) was suspended in 80 mL carbon tetrachloride, and heated to reflux for 6 hours. The reaction mixture was filtered, concentrated, and the residue was dissolved in ethyl acetate and washed with NaHCO3, H2O, saturated NaCl, and dried over MgSO4. The solvent was evaporated and residue was eluted with 10% ethyl acetate in hexanes on a silica gel column to afford 1.70 g of methyl 4'-(bromomethyl)biphenyl-2-carboxylate as a yellow oil with a mass ion (ES+) of 305.0 for M+H+. [0187] To a stirred solution of 2-amino-3-nitropyridine (0.278 g, 2.0 mmol) in DMF (2 mL) at 0 C., sodium hydride (80% dispersion in mineral oil, 0.066 g, 2.1 mmol) was added, and stirred at 0 C. for 30 minutes. A solution of methyl 4'-(bromomethyl)biphenyl-2-carboxylate (0.610 g, 2 mmol) in DMF (0.5 ml) was added, and stirring continued at 0 C. for another 2 hr. The reaction was quenched by saturated NH4Cl and partitioned between ethyl acetate and water. The organic extract was washed with brine, dried over MgSO4, filtered and concentrated under vacuum. The residue was eluted on silica gel with 25% ethyl acetate in hexanes to provide 0.305 g methyl 4'-[(3-nitropyridin-2-yl)amino]methyl}-biphenyl-2-carboxylate as a yellow solid with a mass ion (ES+) of 364.1 for M+H+. [0188] To a solution of the above product (0.676 g, 1.0 mmol) in ethyl acetate (10 mL) and ethanol (190 ml), Raney 2800 nickel (slurry in water) was added and stirred under H2 (balloon) for 1 hr. The black suspension was filtered and the filtrate was concentrated under vacuum. The residue was subjected to silica gel chromatography eluted with 50% ethyl acetate in hexanes to give 0.27 g methyl 4'-[(3-aminopyridin-2-yl)amino]methyl}-biphenyl-2-carboxylate as a yellow solid with a mass ion (ES+) of 334.1 for M+H+. [0189] A solution of beta-CN-propionic methyl ester (226 mg, 2.0 mmol) in MeOH (3 mL), 4 N NaOH (1 ml) and water (4 ml) was stirred 7 hr at rt and neutralized with 6N HCl. The solvent was concentrated under vacuum to give a white residue. The white residue was added to a solution of methyl 4'-[(3-amino-4-pyridin-2-yl)amino)methyl]biphenyl-2-carboxylate (0.167 g, 0.5 mmol) in DMF (1 ml), and 1-ethyl-(3-dimethylaminopropyl)carbodimide hydrochloride (134 mg, 0.7 mmol), 1-hydroxy-7-azabenzotriazole (68 mg, 0.5 mmol), N,N-diisopropylethylamine was added until pH=9.5. The resulting solution was stirred for 3 hr at rt and the reaction mixture was partitioned between ethyl acetate and water. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under vacuum. Purification was achieved by preparative HPLC with a small amount or trifluoroacetic acid to give the title compound as the trifluoracetic acid salt that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 415.3 for M+H+: 1H NMR (400 MHz, DMSO-d6) delta 2.77 (t, J=7.33 Hz, 2H), 2.84 (t, J=7.44 Hz, 2H), 3.62 (s, 3H), 4.79(s, 2H). 6.89 (br s, 1H), 7.28 (d, J=7.57, 2H), 7.46 (m, 4H), 7.62(dd, J=7.57 Hz, 1H), 7.74 (d, J=7.6 Hz, 1H), 7.82 (d, J=7.2 Hz, 1H), 7.91 (s, 1H), 9.3 (br s, 1H)

Reference： [1]Patent: US2004/34064,2004,A1 .Location in patent: Page/Page column 14
[2]Patent: US2004/44041,2004,A1 .Location in patent: Page/Page column 14
[3]Bioorganic and Medicinal Chemistry Letters,2000,vol. 10,p. 2149 - 2152
[4]Journal of Medicinal Chemistry,2001,vol. 44,p. 703 - 714

8
MeO-PEG₅₀₀₀-[2-(4-methylphenyl)benzoate] [ No CAS ]
[ 114772-34-8 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium cyanide In methanol at 20℃;

Reference： [1]Sieber, Frank; Wentworth Jr., Paul; Janda, Kim D. [Molecules, 2000, vol. 5, # 8, p. 1018 - 1032]

9
[ 610-94-6 ]
[ 5720-05-8 ]
[ 114772-34-8 ]

Yield	Reaction Conditions	Operation in experiment
98%	With tetra-butylammonium acetate In ethanol at 120℃; for 0.166667h; microwave irradiation;
93%	With potassium fluoride In toluene at 80℃; for 1h;
62%	With sodium carbonate In tetrahydrofuran; water at 60℃; for 10h;

57%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; sodium carbonate In water; acetonitrile Reflux;
52%	With sodium carbonate In tetrahydrofuran at 60℃; for 4h;
	With potassium fluoride; johnphos In tetrahydrofuran at 20℃; for 24h;

Reference： [1]Baxendale, Ian R.; Griffiths-Jones, Charlotte M.; Ley, Steven V.; Tranmer, Geoffrey K. [Chemistry - A European Journal, 2006, vol. 12, # 16, p. 4407 - 4416]
[2]Suzuki, Ken; Fontaine, Arnaud; Hori, Yoji; Kobayashi, Tohru [Synlett, 2007, # 20, p. 3206 - 3208]
[3]Fairlamb, Ian J.S.; Kapdi, Anant R.; Lynam, Jason M.; Taylor, Richard J.K.; Whitwood, Adrian C. [Tetrahedron, 2004, vol. 60, # 27, p. 5711 - 5718]
[4]George, Stephen R. D.; Elton, Timothy E.; Harper, Jason B. [Organic and Biomolecular Chemistry, 2015, vol. 13, # 43, p. 10745 - 10750]
[5]Beeby, Andrew; Bettington, Sylvia; Fairlamb, Ian J. S.; Goeta, Andres E.; Kapdi, Anant R.; Niemelae, Elina H.; Thompson, Amber L. [New Journal of Chemistry, 2004, vol. 28, # 5, p. 600 - 605]
[6]Charton, Julie; Girault-Mizzi, Sophie; Debreu-Fontaine, Marie-Ange; Foufelle, Fabienne; Hainault, Isabelle; Bizot-Espiard, Jean-Guy; Caignard, Daniel-Henri; Sergheraert, Christian [Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 13, p. 4490 - 4518]

10
[ 610-97-9 ]
[ 5720-05-8 ]
[ 114772-34-8 ]

Yield	Reaction Conditions	Operation in experiment
27%	With tris(dibenzylideneacetone)dipalladium⁽⁰⁾ chloroform complex; potassium carbonate; N-benzyl-N-(1-octynyl)-p-toluenesulfonamide In water; acetonitrile at 0 - 70℃; for 18h; Inert atmosphere;
	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In tetrahydrofuran; water at 20 - 80℃; Schlenk technique; Inert atmosphere;
	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In tetrahydrofuran; water at 60℃; Schlenk technique;

	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In tetrahydrofuran; water at 80℃; for 12h; Inert atmosphere;
	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In tetrahydrofuran; water at 60℃; Schlenk technique;
	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In tetrahydrofuran at 65℃; for 12h; Inert atmosphere;
	With potassium phosphate; palladium diacetate; triphenylphosphine In toluene at 80℃; Inert atmosphere; Schlenk technique;	2. Preparation of starting materials^[1][2] General procedure: To a 50 mL oven-dried Schlenk flask equipped with a magnetic stir bar, were added methyl 2-iodobenzoate (2.62 g, 10 mmol), arylboronic acid (15 mmol),Pd(OAc)2 (22 mg, 1 mol%), PPh3 (52 mg, 2 mol%) and K3PO4 (4.24 g, 20 mmol).The Schlenk flask was evacuated and backfilled with N2 for 3 times. Then toluene (20mL) was added. The reaction mixture was heated at 80 C. The reaction progress wasmonitored by thin-layer chromatography (TLC) analysis. After the reaction was completed, the mixture was cooled to room temperature. Then the reaction mixture was concentrated on a rotary evaporator, and purified by column chromatography(PE/EtOAc = 50/1) to give the desired ester.KOH (3.0 g, 75 mmol), MeOH (20 mL) and the desired ester were added to a50-mL of flask, and the mixture was heated at 80 oC for 2-12 h (TLC monitored). The reaction mixture was cooled to room temperature. Then the reaction mixture was acidified and extracted with DCM (3 x 30 mL). Combined organic extract was dried with Na2SO4, concentrated on a rotary evaporator and the residue was purified bycolumn chromatography on silica gel using PE/EtOAc = 5/1 as eluent to afford theproduct. To a 50 mL oven-dried Schlenk flask equipped with a magnetic stir bar, were added methyl 2-iodobenzoate (10 mmol), phenylboronic acid (15 mmol), Pd(OAc)2(112 mg, 5 mol%), DPPF (338 mg, 6 mol%) and K3PO4 (20 mmol). The Schlenk flask was evacuated and backfilled with N2 for 3 times. Then 1,2-dimethoxyethane (30 mL)was added. The reaction mixture was heated at 80 C. The reaction progress was monitored by thin-layer chromatography (TLC) analysis. After the reaction was completed, the mixture was cooled to room temperature. Then the reaction mixture was concentrated on a rotary evaporator, and purified by column chromatography(PE/EtOAc = 50/1) to give the desired ester.KOH (3.0 g, 75 mmol), MeOH (20 mL) and the desired ester were added to a 50-mL of flask, and the mixture was heated at 80 oC for 2-12 h (TLC monitored). The reaction mixture was cooled to room temperature. Then the reaction mixture was acidified and extracted with DCM (3 x 30 mL). Combined organic extract was dried with Na2SO4, concentrated on a rotary evaporator and the residue was purified by column chromatography on silica gel using PE/EtOAc = 5/1 as eluent to afford theproduct.Other reagents and solvents were purchased from commercial supplier and used without any further treatment.
	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In tetrahydrofuran; water at 80℃; Inert atmosphere;	General Procedure for the Preparation of 2-Arylbenzoic Acids (Precursors to 1a-d5, 1b-1f, 1i-1p,1s, or 1t) General procedure: Based on a modified literature procedure,24 a round bottom flask was charged with methyl 2-iodobenzoate (2.6 g, 10mmol), arylboronic acid (10.5mmol), PdCl2(PPh3)2 (0.18 g, 0.25mmol), Na2CO3 (2.1 g, 20mmol) in THF (25 mL) and H2O (25 mL) under nitrogen atmosphere. The mixture was stirred at 80 °C overnight. The resulting reaction mixture was cooled to room temperature before H2O was added, and the mixture was extracted with EtOAc. The organic layer was dried over anhydrous Na2SO4, and the filtrate was evaporated under reduced pressure. The crude material was purified by column chromatography on silica gel (hexane/EtOAc) to afford the corresponding methyl 2-arylbenzoate as a colorless liquid. Next, to a solution of the methyl 2-arylbenzoate (8mmol) in MeOH (32 mL), 1M NaOH in H2O (32 mL) was added slowly. The resultant mixture was stirred at 50 °C overnight. The resulting reaction mixture was then acidified using an aqueous solution of HCl (1 M) and extracted with CH2Cl2. The combined organic layer was dried over anhydrous Na2SO4, and the filtrate was evaporated under reduced pressure. The crude material was purified by recrystallization from hexane/EtOAc to afford the desired 2-arylbenzoic acid as a white solid.
	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In 1,4-dioxane; water at 100℃; for 12h; Inert atmosphere;

Reference： [1]Wakamatsu, Hideaki; Takahashi, Ayano; Ishii, Ayaka; Kikuchi, Youhei; Sasaki, Madoka; Saito, Yukako; Natori, Yoshihiro; Yoshimura, Yuichi [Organic Letters, 2020, vol. 22, # 14, p. 5299 - 5303]
[2]Zhao, Jian; Yue, Dawei; Campo, Marino A.; Larock, Richard C. [Journal of the American Chemical Society, 2007, vol. 129, # 16, p. 5288 - 5295]
[3]Wang, Yang; Gulevich, Anton V.; Gevorgyan, Vladimir [Chemistry - A European Journal, 2013, vol. 19, # 47, p. 15836 - 15840]
[4]Dai, Jian-Jun; Xu, Wen-Tao; Wu, Ya-Dong; Zhang, Wen-Man; Gong, Ying; He, Xia-Ping; Zhang, Xin-Qing; Xu, Hua-Jian [Journal of Organic Chemistry, 2015, vol. 80, # 2, p. 911 - 919]
[5]Ramirez, Nieves P.; Bosque, Irene; Gonzalez-Gomez, Jose C. [Organic Letters, 2015, vol. 17, # 18, p. 4550 - 4553]
[6]Tao, Xiang-Zhang; Dai, Jian-Jun; Zhou, Jie; Xu, Jun; Xu, Hua-Jian [Chemistry - A European Journal, 2018, vol. 24, # 27, p. 6932 - 6935]
[7]Yang, Dongyan; Zhao, Bin; Fan, Zhijin; Yu, Bin; Zhang, Nailou; Li, Zhengming; Zhu, Yilin; Zhou, Jinghui; Kalinina, Tatiana A.; Glukhareva, Tatiana V. [Journal of Agricultural and Food Chemistry, 2019, vol. 67, # 47, p. 13185 - 13194]
[8]Chen, Bajin; Hu, Baoxiang; Hu, Xinquan; Jin, Liqun; Li, Meichao; Shen, Zhenlu; Sun, Nan; Wang, Shengpeng; Wang, Yiqing [Synlett, 2020, vol. 31, # 3, p. 261 - 266]
[9]Hayakawa, Kazuki; Ikai, Kana; Ogiwara, Yohei; Sakai, Norio; Sakurai, Yuka [Bulletin of the Chemical Society of Japan, 2021, vol. 94, # 7, p. 1882 - 1893]
[10]Bera, Shyamal Kanti; Mal, Prasenjit [Journal of Organic Chemistry, 2021, vol. 86, # 20, p. 14144 - 14159]

11
[ 114772-34-8 ]
C₂₀H₁₅⁽²⁾HIN [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: LiAlD₄ 2: pyridinium chlorochromate 3: MgSO₄ / toluene / 100 °C

Reference： [1]Zhao, Jian; Yue, Dawei; Campo, Marino A.; Larock, Richard C. [Journal of the American Chemical Society, 2007, vol. 129, # 16, p. 5288 - 5295]

12
[ 7335-25-3 ]
[ 114772-34-8 ]

Reference： [1]Tetrahedron,2002,vol. 58,p. 5779 - 5787

13
[ 5720-05-8 ]
[ 114772-34-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: K₃PO₄; 2-(dicyclohexylphosphino)biphenyl based D-gluconamide / Pd(OAc)2 / H₂O / 16 h / 80 °C 2: BF₃*OEt₂ / Heating
	Multi-step reaction with 2 steps 1: PdCl₂; aq. NaOH 2: benzene; methanol; hexane
	Multi-step reaction with 2 steps 1: PdCl₂; aq. NaOH 2: MeOH / hexane; benzene

	Multi-step reaction with 2 steps 1: palladium diacetate; triphenylphosphine / acetonitrile 2: water / Acidic conditions
	Multi-step reaction with 2 steps 1.1: palladium diacetate / water / 0.08 h / 20 °C / Inert atmosphere 1.2: 5 h / Inert atmosphere; Reflux 2.1: sulfuric acid / 5 h / Reflux

Reference： [1]Nishimura, Masato; Ueda, Masato; Miyaura, Norio [Tetrahedron, 2002, vol. 58, # 29, p. 5779 - 5787]
[2]Santhosh; Paul; De Clercq; Pannecouque; Witvrouw; Loftus; Turpin; Buckheit, Jr.; Cushman [Journal of Medicinal Chemistry, 2001, vol. 44, # 5, p. 703 - 714]
[3]Paul, Gitendra C.; De Clercq, Erik; Pannecouque, Christophe; Witvrouw, Myriam; Loftus, Tracy L.; Turpin, Jim A.; Buckheit Jr., Robert W.; Cushman, Mark [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 18, p. 2149 - 2152]
[4]Shashikumar, Nellisara D; Krishnamurthy, Ganganaika; BhojyaNaik, Halehatti S; Lokesh, Mayasandra R; Jithendrakumara, Kaginalli S [Journal of Chemical Sciences, 2014, vol. 126, # 1, p. 205 - 212]
[5]Obermoser, Victoria; Urban, Margarethe E.; Murgueitio, Manuela S.; Wolber, Gerhard; Kintscher, Ulrich; Gust, Ronald [European Journal of Medicinal Chemistry, 2016, vol. 124, p. 138 - 152]

14
[ 88-65-3 ]
[ 114772-34-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: PdCl₂; aq. NaOH 2: benzene; methanol; hexane
	Multi-step reaction with 2 steps 1: PdCl₂; aq. NaOH 2: MeOH / hexane; benzene
	Multi-step reaction with 2 steps 1: sulfuric acid / 5 h / Reflux 2: palladium diacetate; sodium carbonate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane / acetonitrile; water / Reflux

Multi-step reaction with 2 steps 1.1: palladium diacetate / water / 0.08 h / 20 °C / Inert atmosphere 1.2: 5 h / Inert atmosphere; Reflux 2.1: sulfuric acid / 5 h / Reflux

Reference： [1]Santhosh; Paul; De Clercq; Pannecouque; Witvrouw; Loftus; Turpin; Buckheit, Jr.; Cushman [Journal of Medicinal Chemistry, 2001, vol. 44, # 5, p. 703 - 714]
[2]Paul, Gitendra C.; De Clercq, Erik; Pannecouque, Christophe; Witvrouw, Myriam; Loftus, Tracy L.; Turpin, Jim A.; Buckheit Jr., Robert W.; Cushman, Mark [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 18, p. 2149 - 2152]
[3]George, Stephen R. D.; Elton, Timothy E.; Harper, Jason B. [Organic and Biomolecular Chemistry, 2015, vol. 13, # 43, p. 10745 - 10750]
[4]Obermoser, Victoria; Urban, Margarethe E.; Murgueitio, Manuela S.; Wolber, Gerhard; Kintscher, Ulrich; Gust, Ronald [European Journal of Medicinal Chemistry, 2016, vol. 124, p. 138 - 152]

15
[ 114772-34-8 ]
[ 114772-35-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 47 percent / 1 N NaOH / ethanol / 18 h / Ambient temperature 2: (COCl)2 / CH₂Cl₂; dimethylformamide / 1 h
	Multi-step reaction with 2 steps 1: sodium hydroxide / ethanol / 5 h / Reflux 2: thionyl chloride / 4 h
	Multi-step reaction with 2 steps 1: sodium hydroxide; water / tetrahydrofuran / 80 °C 2: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 2 h / 20 °C / Cooling with ice

Multi-step reaction with 2 steps 1: lithium hydroxide; water / tetrahydrofuran; methanol / 8 h / 70 °C 2: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 8 h / 0 - 20 °C / Inert atmosphere

Reference： [1]Matsuhisa, Akira; Tanaka, Akihiro; Kikuchi, Kazumi; Shimada, Yoshiaki; Yatsu, Takeyuki; Yanagisawa, Isao [Chemical and Pharmaceutical Bulletin, 1997, vol. 45, # 11, p. 1870 - 1874]
[2]George, Stephen R. D.; Elton, Timothy E.; Harper, Jason B. [Organic and Biomolecular Chemistry, 2015, vol. 13, # 43, p. 10745 - 10750]
[3]Yang, Dongyan; Zhao, Bin; Fan, Zhijin; Yu, Bin; Zhang, Nailou; Li, Zhengming; Zhu, Yilin; Zhou, Jinghui; Kalinina, Tatiana A.; Glukhareva, Tatiana V. [Journal of Agricultural and Food Chemistry, 2019, vol. 67, # 47, p. 13185 - 13194]
[4]Bera, Shyamal Kanti; Mal, Prasenjit [Journal of Organic Chemistry, 2021, vol. 86, # 20, p. 14144 - 14159]

16
[ 114772-34-8 ]
[ 133690-73-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: 99 percent / NaOH / H₂O; methanol / Heating 2: 94 percent / sulfuric acid / diethyl ether / 25 °C 3: NBS, AIBN / CCl₄ / Heating 4: 100 percent / NaN₃ / dimethylformamide / 24 h / Ambient temperature 5: 100 percent / H₂ / 10percent Pd/C / ethanol / 20 h / 2068.6 Torr

Reference： [1]Huang, Horng-Chih; Reitz, David B.; Chamberlain, Timothy S.; Olins, Gillian M.; Corpus. Valerie M.; et al. [Journal of Medicinal Chemistry, 1993, vol. 36, # 15, p. 2172 - 2181]

17
[ 114772-34-8 ]
4'-Isocyanatomethyl-biphenyl-2-carboxylic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: 99 percent / NaOH / H₂O; methanol / Heating 2: 94 percent / sulfuric acid / diethyl ether / 25 °C 3: NBS, AIBN / CCl₄ / Heating 4: 100 percent / NaN₃ / dimethylformamide / 24 h / Ambient temperature 5: 100 percent / H₂ / 10percent Pd/C / ethanol / 20 h / 2068.6 Torr 6: pyridine / toluene; CH₂Cl₂ / 1 h / 0 °C

Reference： [1]Huang, Horng-Chih; Reitz, David B.; Chamberlain, Timothy S.; Olins, Gillian M.; Corpus. Valerie M.; et al. [Journal of Medicinal Chemistry, 1993, vol. 36, # 15, p. 2172 - 2181]

18
[ 114772-34-8 ]
4'-<(3-butyl-4,5-dihydro-5-oxo-1,2,4-triazol-4-yl)methyl><1,1'-biphenyl>-2-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1: 99 percent / NaOH / H₂O; methanol / Heating 2: 94 percent / sulfuric acid / diethyl ether / 25 °C 3: NBS, AIBN / CCl₄ / Heating 4: 100 percent / NaN₃ / dimethylformamide / 24 h / Ambient temperature 5: 100 percent / H₂ / 10percent Pd/C / ethanol / 20 h / 2068.6 Torr 6: pyridine / toluene; CH₂Cl₂ / 1 h / 0 °C 7: pyridine / toluene; CH₂Cl₂ / 20 h / Ambient temperature 8: NaOCH₃ / methanol / 30 h / Heating 9: 87 percent / trifluoroacetic acid / CHCl₃ / 20 h / Ambient temperature

Reference： [1]Huang, Horng-Chih; Reitz, David B.; Chamberlain, Timothy S.; Olins, Gillian M.; Corpus. Valerie M.; et al. [Journal of Medicinal Chemistry, 1993, vol. 36, # 15, p. 2172 - 2181]

19
[ 114772-34-8 ]
4'-<(1,3-dibutyl-4,5-dihydro-5-oxo-1H-1,2,4-triazol-4-yl)methyl><1,1'-biphenyl>-2-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 10 steps 1: 99 percent / NaOH / H₂O; methanol / Heating 2: 94 percent / sulfuric acid / diethyl ether / 25 °C 3: NBS, AIBN / CCl₄ / Heating 4: 100 percent / NaN₃ / dimethylformamide / 24 h / Ambient temperature 5: 100 percent / H₂ / 10percent Pd/C / ethanol / 20 h / 2068.6 Torr 6: pyridine / toluene; CH₂Cl₂ / 1 h / 0 °C 7: pyridine / toluene; CH₂Cl₂ / 20 h / Ambient temperature 8: NaOCH₃ / methanol / 30 h / Heating 9: t-BuOK / dimethylformamide; tetrahydrofuran / 17 h / 25 °C 10: 100 percent / trifluoroacetic acid / CHCl₃ / 15 h / Ambient temperature

Reference： [1]Huang, Horng-Chih; Reitz, David B.; Chamberlain, Timothy S.; Olins, Gillian M.; Corpus. Valerie M.; et al. [Journal of Medicinal Chemistry, 1993, vol. 36, # 15, p. 2172 - 2181]

20
[ 114772-34-8 ]
[ 139476-14-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1: 99 percent / NaOH / H₂O; methanol / Heating 2: 94 percent / sulfuric acid / diethyl ether / 25 °C 3: NBS, AIBN / CCl₄ / Heating 4: 100 percent / NaN₃ / dimethylformamide / 24 h / Ambient temperature 5: 100 percent / H₂ / 10percent Pd/C / ethanol / 20 h / 2068.6 Torr 6: pyridine / toluene; CH₂Cl₂ / 1 h / 0 °C 7: pyridine / toluene; CH₂Cl₂ / 20 h / Ambient temperature 8: NaOCH₃ / methanol / 30 h / Heating

Reference： [1]Huang, Horng-Chih; Reitz, David B.; Chamberlain, Timothy S.; Olins, Gillian M.; Corpus. Valerie M.; et al. [Journal of Medicinal Chemistry, 1993, vol. 36, # 15, p. 2172 - 2181]

21
[ 114772-34-8 ]
[ 139476-13-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: 99 percent / NaOH / H₂O; methanol / Heating 2: 94 percent / sulfuric acid / diethyl ether / 25 °C 3: NBS, AIBN / CCl₄ / Heating 4: 100 percent / NaN₃ / dimethylformamide / 24 h / Ambient temperature 5: 100 percent / H₂ / 10percent Pd/C / ethanol / 20 h / 2068.6 Torr 6: pyridine / toluene; CH₂Cl₂ / 1 h / 0 °C 7: pyridine / toluene; CH₂Cl₂ / 20 h / Ambient temperature

Reference： [1]Huang, Horng-Chih; Reitz, David B.; Chamberlain, Timothy S.; Olins, Gillian M.; Corpus. Valerie M.; et al. [Journal of Medicinal Chemistry, 1993, vol. 36, # 15, p. 2172 - 2181]

22
[ 114772-34-8 ]
[ 139476-15-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1: 99 percent / NaOH / H₂O; methanol / Heating 2: 94 percent / sulfuric acid / diethyl ether / 25 °C 3: NBS, AIBN / CCl₄ / Heating 4: 100 percent / NaN₃ / dimethylformamide / 24 h / Ambient temperature 5: 100 percent / H₂ / 10percent Pd/C / ethanol / 20 h / 2068.6 Torr 6: pyridine / toluene; CH₂Cl₂ / 1 h / 0 °C 7: pyridine / toluene; CH₂Cl₂ / 20 h / Ambient temperature 8: NaOCH₃ / methanol / 30 h / Heating 9: t-BuOK / dimethylformamide; tetrahydrofuran / 17 h / 25 °C

Reference： [1]Huang, Horng-Chih; Reitz, David B.; Chamberlain, Timothy S.; Olins, Gillian M.; Corpus. Valerie M.; et al. [Journal of Medicinal Chemistry, 1993, vol. 36, # 15, p. 2172 - 2181]

23
[ 114772-34-8 ]
[ 16191-28-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 42.55 g / diisobutylaluminum hydride / toluene / 0.25 h / -78 - -70 °C 2: pyridinium chlorochromate / CH₂Cl₂ / 0.5 h / 25 °C
	With diisobutylaluminium hydride In methanol; water; toluene	177.A Preparation of 4'-Methylbiphenyl-2-carboxaldehyde Part A Preparation of 4'-Methylbiphenyl-2-carboxaldehyde Methyl 4'-methylbiphenyl-2-carboxylate (20.00 g, 88 mmol, 1 eq) was dissolved in dry toluene (250 mL) and cooled to -78°: Diisobutylaluminum hydride (1.0M in toluene, 220.0 mL, 220 mmol, 2.2 eq) was then dripped in slowly over 25 minutes keeping the temperature under -70°. When the addition was complete, the mixture was stirred at -78° for 15 minutes and then methanol (10 mL) was added cautiously. When gas evolution was complete, the mixture was poured into a solution of Rochelle salt (100 mL of saturated solution plus 600 mL water). The mixture was stirred or shaken until an extractable solution was obtained. The layers were separated and the aqueous layer extracted with ether (2*200 mL). The organic layers were combined, dried (MgSO4) and the solvent removed in vacuo to yield 16.7 g of a light yellow oil. NMR (200 MHz, CDCl3)δ7.56-7.16 (m, 8H); 4.59 (s, 2H); 2.40 (s, 3H); 1.74 (s, 1H). This oil (16.7 g, 84 mmol, 1 eq) was subsequently oxidized by dissolving in methylene chloride (100 mL) and stirring with manganese dioxide (7.34 g, 84 mmol, 1 eq). After stirring for one day at room temperature, more manganese dioxide (14.68 g, 168 mmol, 2 eq) was added. The next day, 14.68 g more of manganese dioxide was again added. After another day of stirring, the reaction was filtered through Celite and the filtrate evaporated to an oil. The oil was chromatographed in 9:1 hexane/ethyl acetate over silica gel to yield 13.4 g of a light yellow opaque oil.
	With diisobutylaluminium hydride In methanol; water; toluene	177.A PART A: PART A: Preparation of 4'-Methylbiphenyl-2-carboxaldehyde Methyl 4'-methylbiphenyl-2-carboxylate (20.00 g, 88 mmol, 1 eq) was dissolved in dry toluene (250 mL) and cooled to -78°: Diisobutylaluminum hydride (1.0M in toluene, 220.0 mL, 220 mmol, 2.2 eq) was then dripped in slowly over 25 minutes keeping the temperature under -70°. When the addition was complete, the mixture as stirred at -78° for 15 minutes and then methanol (10 mL) was added cautiously. When gas evolution was complete, the mixture was poured into a solution of Rochelle salt (100 mL of saturated solution plug 600 mL water). The mixture as stirred or shaken until an extractable solution was obtained. The layers were separated and the aqueous layer extracted with ether (2*200 mL). The organic layers were combined, dried (MgSO4) and the solvent removed in vacuo to yield 16.7 g of a light yellow oil. NMR (200 MHz, CDCl3) δ 7.56-7.16 (m, 8H); 4.59 (s, 2H); 2.40 (s, 3H); 1.74 (s, 1H). This oil (16.7 g, 84 mmol, 1 eq) was subsequently oxidized by dissolving in methylene chloride (100 mL) and stirring with manganese dioxide (7.34 g, 84 mmol, 1 eq). After stirring for one day at room temperature, more manganese dioxide (14.68 g, 168 mmol, 2 eq) was added. The next day, 14.68 g more of manganese dioxide was again added. After another day of stirring, the reaction was filtered through Celite and the filtrate evaporated to an oil. The oil was chromatographed in 9:1 hexane/ethyl acetate over silica gel to yield 13.4 g of a light yellow opaque oil.

Reference： [1]Carini, David J.; Duncia, John V.; Aldrich, Paul E.; Chiu, Andrew T.; Johnson, Alexander L.; et al. [Journal of Medicinal Chemistry, 1991, vol. 34, # 8, p. 2525 - 2547]
[2]Current Patent Assignee: DUPONT DE NEMOURS INC - US5138069, 1992, A
[3]Current Patent Assignee: DUPONT DE NEMOURS INC - US5128355, 1992, A

24
[ 114772-34-8 ]
[ 114799-00-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: N-bromosuccinimide, dibenzoyl peroxide / CCl₄ / 3 h / Heating 2: 1.) sodium methoxide / 1.) DMF, 25 deg C, 0.25 h, 2.) DMF, 40 deg C, 4 h 3: 79 percent / H₂ / 10percent Pd/C / methanol / 3.5 h / 25 °C / 760 Torr 4: 69 percent / 10percent aq. NaOH / ethanol / 5 h / Heating

Reference： [1]Carini, David J.; Duncia, John V.; Aldrich, Paul E.; Chiu, Andrew T.; Johnson, Alexander L.; et al. [Journal of Medicinal Chemistry, 1991, vol. 34, # 8, p. 2525 - 2547]

25
[ 114772-34-8 ]
[ 114772-45-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: N-bromosuccinimide, dibenzoyl peroxide / CCl₄ / 3 h / Heating 2: 1.) sodium methoxide / 1.) DMF, 25 deg C, 0.25 h, 2.) DMF, 40 deg C, 4 h 3: 79 percent / H₂ / 10percent Pd/C / methanol / 3.5 h / 25 °C / 760 Torr

Reference： [1]Carini, David J.; Duncia, John V.; Aldrich, Paul E.; Chiu, Andrew T.; Johnson, Alexander L.; et al. [Journal of Medicinal Chemistry, 1991, vol. 34, # 8, p. 2525 - 2547]

26
[ 114772-34-8 ]
[ 114799-97-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: N-bromosuccinimide, dibenzoyl peroxide / CCl₄ / 3 h / Heating 2: 1.) sodium methoxide / 1.) DMF, 25 deg C, 0.25 h, 2.) DMF, 40 deg C, 4 h 3: 97 percent / thionyl chloride / CHCl₃ / 4 h / 25 °C 4: sodium azide / dimethylsulfoxide / 16 h / 25 °C 5: H₂ / 10percent Pd/C / methanol / 1 h / 25 °C / 760 Torr 6: 1.76 g / 0.5 N methanolic KOH / H₂O / 18 h / Heating

Reference： [1]Carini, David J.; Duncia, John V.; Aldrich, Paul E.; Chiu, Andrew T.; Johnson, Alexander L.; et al. [Journal of Medicinal Chemistry, 1991, vol. 34, # 8, p. 2525 - 2547]

27
[ 114772-34-8 ]
[ 114772-73-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: N-bromosuccinimide, dibenzoyl peroxide / CCl₄ / 3 h / Heating 2: 1.) sodium methoxide / 1.) DMF, 25 deg C, 0.25 h, 2.) DMF, 40 deg C, 4 h 3: 97 percent / thionyl chloride / CHCl₃ / 4 h / 25 °C 4: sodium azide / dimethylsulfoxide / 16 h / 25 °C 5: H₂ / 10percent Pd/C / methanol / 1 h / 25 °C / 760 Torr

Reference： [1]Carini, David J.; Duncia, John V.; Aldrich, Paul E.; Chiu, Andrew T.; Johnson, Alexander L.; et al. [Journal of Medicinal Chemistry, 1991, vol. 34, # 8, p. 2525 - 2547]

28
[ 114772-34-8 ]
[ 114799-23-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: N-bromosuccinimide, dibenzoyl peroxide / CCl₄ / 3 h / Heating 2: 1.) sodium methoxide / 1.) DMF, 25 deg C, 0.25 h, 2.) DMF, 40 deg C, 4 h 3: 97 percent / thionyl chloride / CHCl₃ / 4 h / 25 °C 4: sodium azide / dimethylsulfoxide / 16 h / 25 °C 5: H₂ / 10percent Pd/C / methanol / 1 h / 25 °C / 760 Torr 6: 1.76 g / 0.5 N methanolic KOH / H₂O / 18 h / Heating 7: 1.000 N aq. NaOH / tetrahydrofuran / 16 h / 25 °C

Reference： [1]Carini, David J.; Duncia, John V.; Aldrich, Paul E.; Chiu, Andrew T.; Johnson, Alexander L.; et al. [Journal of Medicinal Chemistry, 1991, vol. 34, # 8, p. 2525 - 2547]

29
[ 114772-34-8 ]
[ 114799-31-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: N-bromosuccinimide, dibenzoyl peroxide / CCl₄ / 3 h / Heating 2: 1.) sodium methoxide / 1.) DMF, 25 deg C, 0.25 h, 2.) DMF, 40 deg C, 4 h 3: 97 percent / thionyl chloride / CHCl₃ / 4 h / 25 °C 4: sodium azide / dimethylsulfoxide / 16 h / 25 °C 5: H₂ / 10percent Pd/C / methanol / 1 h / 25 °C / 760 Torr 6: 55 percent / CHCl₃ / 72 h / 25 °C 7: 0.5 N methanolic KOH / H₂O / 18 h / Heating

Reference： [1]Carini, David J.; Duncia, John V.; Aldrich, Paul E.; Chiu, Andrew T.; Johnson, Alexander L.; et al. [Journal of Medicinal Chemistry, 1991, vol. 34, # 8, p. 2525 - 2547]

30
[ 114772-34-8 ]
[ 124750-41-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: N-bromosuccinimide, dibenzoyl peroxide / CCl₄ / 3 h / Heating 2: 1.) sodium methoxide / 1.) DMF, 25 deg C, 0.25 h, 2.) DMF, 40 deg C, 4 h 3: 97 percent / thionyl chloride / CHCl₃ / 4 h / 25 °C 4: sodium azide / dimethylsulfoxide / 16 h / 25 °C 5: H₂ / 10percent Pd/C / methanol / 1 h / 25 °C / 760 Torr 6: 55 percent / CHCl₃ / 72 h / 25 °C

Reference： [1]Carini, David J.; Duncia, John V.; Aldrich, Paul E.; Chiu, Andrew T.; Johnson, Alexander L.; et al. [Journal of Medicinal Chemistry, 1991, vol. 34, # 8, p. 2525 - 2547]

31
[ 114772-34-8 ]
[ 128764-56-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: N-bromosuccinimide, dibenzoyl peroxide / CCl₄ / 3 h / Heating 2: 1.) sodium methoxide / 1.) DMF, 25 deg C, 0.25 h, 2.) DMF, 40 deg C, 4 h 3: 97 percent / thionyl chloride / CHCl₃ / 4 h / 25 °C 4: sodium azide / dimethylsulfoxide / 16 h / 25 °C 5: H₂ / 10percent Pd/C / methanol / 1 h / 25 °C / 760 Torr 6: 75 percent / 1-hydroxybenzotriazole, dicyclohexylcarbodiimide, dicyclohexylcarbodiimide / 96 h / 0 °C 7: 1.68 g / anisole, trifluoroacetic acid / tetrahydrofuran; H₂O / 7 h / 25 °C

Reference： [1]Carini, David J.; Duncia, John V.; Aldrich, Paul E.; Chiu, Andrew T.; Johnson, Alexander L.; et al. [Journal of Medicinal Chemistry, 1991, vol. 34, # 8, p. 2525 - 2547]

32
[ 114772-34-8 ]
[ 128764-55-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: N-bromosuccinimide, dibenzoyl peroxide / CCl₄ / 3 h / Heating 2: 1.) sodium methoxide / 1.) DMF, 25 deg C, 0.25 h, 2.) DMF, 40 deg C, 4 h 3: 97 percent / thionyl chloride / CHCl₃ / 4 h / 25 °C 4: sodium azide / dimethylsulfoxide / 16 h / 25 °C 5: H₂ / 10percent Pd/C / methanol / 1 h / 25 °C / 760 Torr 6: 75 percent / 1-hydroxybenzotriazole, dicyclohexylcarbodiimide, dicyclohexylcarbodiimide / 96 h / 0 °C

Reference： [1]Carini, David J.; Duncia, John V.; Aldrich, Paul E.; Chiu, Andrew T.; Johnson, Alexander L.; et al. [Journal of Medicinal Chemistry, 1991, vol. 34, # 8, p. 2525 - 2547]

33
[ 114772-34-8 ]
[ 128764-54-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1: N-bromosuccinimide, dibenzoyl peroxide / CCl₄ / 3 h / Heating 2: 1.) sodium methoxide / 1.) DMF, 25 deg C, 0.25 h, 2.) DMF, 40 deg C, 4 h 3: 97 percent / thionyl chloride / CHCl₃ / 4 h / 25 °C 4: sodium azide / dimethylsulfoxide / 16 h / 25 °C 5: H₂ / 10percent Pd/C / methanol / 1 h / 25 °C / 760 Torr 6: 75 percent / 1-hydroxybenzotriazole, dicyclohexylcarbodiimide, dicyclohexylcarbodiimide / 96 h / 0 °C 7: 1.68 g / anisole, trifluoroacetic acid / tetrahydrofuran; H₂O / 7 h / 25 °C 8: 1.000 N aq. NaOH / tetrahydrofuran; methanol / 24 h / 50 °C

Reference： [1]Carini, David J.; Duncia, John V.; Aldrich, Paul E.; Chiu, Andrew T.; Johnson, Alexander L.; et al. [Journal of Medicinal Chemistry, 1991, vol. 34, # 8, p. 2525 - 2547]

34
[ 95667-98-4 ]
[ 126403-71-2 ]
[ 114772-34-8 ]

Yield	Reaction Conditions	Operation in experiment
82%	With hydrogenchloride; n-butyllithium; triphenylphosphine; lithium chloride In tetrahydrofuran; water	7 Preparation of methyl 2-(4-methylphenyl)benzoate EXAMPLE 7 Preparation of methyl 2-(4-methylphenyl)benzoate A mixture of nickel chloride (0.11 g, 0.85 mmoles), triphenylphosphine (0.44 g, 1.7 mmoles), and dry tetrahydrofuran (25 ml), at room temperature and under inert atmosphere (nitrogen), is added with 1.6 M n-butyllithium (1.1 ml; 1.7 mmoles); the mixture is kept under stirring for 15', then added with methyl 2-(methanesulfonyloxy)benzoate (10.1 g, 44 mmoles, prepared as described in Example 3) dissolved in dry tetrahydrofuran (10 ml). After further 15' under stirring, the resulting mixture is added to a suspension of p-tolylzinc bromide prepared as described in Example 1, previously added with lithium chloride (2.3 g, 54 mmoles). The resulting mixture is kept at room temperature for 12 hours, then poured into a solution of water (100 ml) and 37% hydrochloric acid (25 ml); the phases are separated, the organic phase is extracted with a water-dichloromethane mixture (50 ml; 50:50); the phases are separated again and the organic one is dried over sodium sulfate and evaporated under vacuum to a residue, to obtain methyl 2-(4-methylphenyl)benzoate as an oil (8.2 g, yield 82%).
82%	With hydrogenchloride; n-butyllithium; triphenylphosphine; lithium chloride In tetrahydrofuran; water	7 Example 7 Example 7 preparation of methyl 2-(4-methylphenyl)benzoate A mixture of nickel chloride (0.11 g, 0.85 mmoles), triphenylphosphine (0.44 g, 1.7 mmoles), and dry tetrahydrofuran (25 ml), at room temperature and under inert atmosphere (nitrogen), is added with 1.6 M n-butyllithium (1.1 ml; 1.7 mmoles); the mixture is kept under stirring for 15', then added with methyl 2-(methanesulfonyloxy)benzoate (10.1 g, 44 mmoles, prepared as described in Example 3) dissolved in dry tetrahydrofuran (10 ml). After further 15' under stirring, the resulting mixture is added to a suspension of p-tolylzinc bromide prepared as described in Example 1, previously added with lithium chloride (2.3 g, 54 mmoles). The resulting mixture is kept at room temperature for 12 hours, then poured into a solution of water (100 ml) and 37% hydrochloric acid (25 ml); the phases are separated, the organic phase is extracted with a water-dichloromethane mixture (50 ml; 50:50); the phases are separated again and the organic one is dried over sodium sulfate and evaporated under vacuum to a residue, to obtain methyl 2-(4-methylphenyl)benzoate as an oil (8.2 g, yield 82%).

Reference： [1]Current Patent Assignee: DIPHARMA FRANCIS S.R.L. - US6433214, 2002, B1
[2]Current Patent Assignee: DIPHARMA FRANCIS S.R.L. - EP1044956, 2000, A1

35
ethylene diaminetetracetic acid [ No CAS ]
[ 106-38-7 ]
[ 610-97-9 ]
[ 114772-34-8 ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium In tetrahydrofuran; hexane; chloroform; water	5.i EXAMPLE 5 (i) A 1.6M solution of butyllithium in hexane (24.0 ml) was added dropwise to a stirred solution of 4-bromotoluene (6.0 g) in dry tetrahydrofuran (THF) (50 ml) at -78° C. under an atmosphere of argon. The temperature was maintained at -78° C. for 20 minutes and then a 1M solution of anhydrous zinc chloride in ether (38.6 ml) was added. The solution was kept at -78° C. for 15 minutes, and then tetrakis (triphenylphosphine)palladium (60 mg) in THF (5 ml) was added, followed by methyl-2-iodobenzoate (6.1 g) in THF (10 ml). The solution was allowed to reach ambient temperature over 1 hour, then heated under reflux for 5 hours. The solvent was removed by evaporation and the residue was dissolved in chloroform (150 ml). The solution was washed with a solution of ethylene diaminetetracetic acid (10 g) in water (100 ml) and the aqueous layer was re-extracted with chloroform (100 ml). The combined organic extracts were dried (MgSO4) and the solvent removed by evaporation. The residue was purified by flash chromatography, eluding with ethyl acetate/hexane (1:9 v/v) to give methyl 4'-methylbiphenyl-2-carboxylate (B) as a colourless oil (4.4 g); NMR: 2.4(s,3H), 3.65(s,3H), 7.2(s,4H), 7.35(m,3H), 7.5(m,1H), 7.8(d,1H).
	With n-butyllithium In tetrahydrofuran; hexane; chloroform; water	1.i EXAMPLE 1 (i) A 1.6M solution of butyllithium in hexane (24.0 ml) was added dropwise to a stirred solution of 4-bromotoluene (6.0 g) in dry tetrahydrofuran (THF) (50 ml) at -78° C. under an atmosphere of argon. The temperature was maintained at -78° C. for 20 minutes and then a 1M solution of anhydrous zinc chloride in ether (38.6 ml) was added. The solution was kept at -78° C. for 15 minutes, and then tetrakis (triphenylphosphine)palladium (60 mg) in THF (5 ml) was added, followed by methyl-2-iodobenzoate (6.1 g) in THF (10 ml). The solution was allowed to reach ambient temperature over 1 hour, then heated under reflux for 5 hours. The solvent was removed by evaporation and the residue was dissolved in chloroform (150 ml). The solution was washed with a solution of ethylene diaminetetracetic acid (10 g) in water (100 ml) and the aqueous layer was re-extracted with chloroform (100 ml). The combined organic extracts were dried (MgSO4) and the solvent removed by evaporation. The residue was purified by flash chromatography, eluding with ethyl acetate/hexane (1:9 v/v) to give methyl 4'-methylbiphenyl-2-carboxylate (B) as a colourless oil (4.4 g); NMR: 2.4(s,3H), 3.65(s,3H), 7.2(s,4H), 7.35(m,3H), 7.5(m,1H), 7.8(d,1H).

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - US5236937, 1993, A
[2]Current Patent Assignee: ASTRAZENECA PLC - US5444071, 1995, A

36
[ 610-96-8 ]
[ 106-38-7 ]
[ 7440-66-6 ]
[ 114772-34-8 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; triphenylphosphine	2 Preparation of methyl 4'-methyl-1,1'-biphenyl-2-carboxylate EXAMPLE 2 Preparation of methyl 4'-methyl-1,1'-biphenyl-2-carboxylate Into a 100 ml flask, 50 ml of dry pyridine, 4.28 g (0.025 mol) of 4-bromotoluene, 4.26 g (0.025 mol) of methyl 2-chlorobenzoate, 0.32 g (0.0025 mol) of anhydrous nickel chloride, 1.31 g (0.005 mol) of triphenylphosphine and 4.90 g (0.075 mol) of zinc powder were charged under a nitrogen atmosphere and stirred at room temperature for 30 minutes. The mixture was heated by an oil bath and reacted at 85° C. for 3 hours. The reaction solution was analyzed by gas chromatography. The results are shown in Table 1. The data confirming the structure are shown below. GC-MS: 226(M+), 195(M+ -31) NMR(CDCl3): δ2.36 (3H,s,CH3), 3.62 (3H,s,OCH3), 7.8-7.2 (8H,m,ArH) IR(KBr): 1730, 1600, 1520, 1485, 1450, 1435, 1295, 1280, 1250, 1190, 1130, 1090, 1050, 820 cm-1

Reference： [1]Current Patent Assignee: KUMIAI CHEMICAL INDUSTRY CO LTD - US5380910, 1995, A

37
[ 34241-39-9 ]
[ 114772-34-8 ]
[ 114772-38-2 ]

Yield	Reaction Conditions	Operation in experiment
59%	With N-Bromosuccinimide; In tetrachloromethane;	EXAMPLE 19 Synthesis of methyl 2-(4'-bromomethylphenyl)benzoate 2.0 g (8.8 mmol) of methyl 2-(4'-methylphenyl)benzoate, 1.6 g (9.0 mmol) of N-bromosuccinimide and 0.05 g of alpha,alpha'-azobis(isobutyronitrile) [another name; 2,2'-azobis(isobutyronitrile)] were dissolved in carbon tetrachloride (110 ml), followed by heating under reflux for 2 hours. The resultant mixture was filtered to remove insolubles, and then vacuum concentration was effected. The residue was recrystallized from a n-hexane/isopropyl ether mixed solvent to give 1.6 g of the title compound (yield; 59%).
	With N-Bromosuccinimide; In tetrachloromethane;	PREPARATION EXAMPLE 9 Methyl 2-(4-bromomethylphenyl)benzoate STR49 2.0 g of methyl 2-(4-methylphenyl)benzoate, 1.6 g of N-bromosuccinimide and 0.05 g of alpha,alpha'-azobis(isobutyronitrile) were heated in 110 ml of carbon tetrachloride under reflux for 2 hr. The succinimide was filtered off. The filtrate was concentrated, and the residue was recrystallized from a mixed solvent of n-hexane-isopropyl ether to prepare 1.6 g of the title compound.

Reference： [1]Patent: US5554757,1996,A
[2]Patent: US5298518,1994,A

38
[ 7148-03-0 ]
[ 114772-34-8 ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid In methanol	P.8 Methyl 2-(4-methylphenyl)benzoate STR48 PREPARATION EXAMPLE 8 Methyl 2-(4-methylphenyl)benzoate STR48 6 g of sulfuric acid in 12 ml of methanol was added to 3.2 g of 2-(4-methylphenyl)benzoic acid [see A. I. Meyers et al., J. Org. Chem., 43, 1372 (1978)], and the mixture was heated under reflux for 8 hr. The refluxed solution was cooled, poured into ice water, weakly alkalified with aqueous ammonia and extracted with ether. The extract was dried over anhydrous magnesium sulfate. The dried extract was concentrated, and the residue was recrystallized from n-hexane to prepare 2.4 g of the title compound.

Reference： [1]Current Patent Assignee: EISAI CO LTD - US5298518, 1994, A

39
[ 128-08-5 ]
[ 114772-34-8 ]
[ 114772-38-2 ]

Yield	Reaction Conditions	Operation in experiment
30 g (100%)	In tetrachloromethane	8 EXAMPLE 8 EXAMPLE 8 2.3 g of methyl 4'-methyl-(1, 1'-biphenyl)-2-carboxylate was dissolved in 900 ml of tetrachloromethane under a nitrogen flow. Then there were added 17.8 g of 1-bromo-2,5-pyrrolidinedione and a catalytic amount of dibenzoyl peroxide. After stirring for 2.5 hours at reflux temperature under a nitrogen atmosphere, the reaction mixture was cooled and filtered. The flitrate was evaporated, yielding >30 g (100%) of methyl 4'-(bromomethyl)[1,1'-biphenyl]-2-carboxylate as a crude residue (interm. 36).
30 g (100%)	In tetrachloromethane	1.b Example 1 22.3 g of methyl 4'-methyl-(1,1'biphenyl)-2-carboxylate were dissolved in 900 ml of tetrachloromethane under a nitrogen flow. Then there were added 17.8 g of 1-bromo-2,5-pyrrolidinedione and a catalytic amount of dibenzoyl peroxide. After stirring for 2.5 hours at reflux temperature under a nitrogen atmosphere, the reaction mixture was cooled and filtered. The filtrate was evaporated, yielding >30 g (100%) of methyl 4'-(bromomethyl)[1,1'-biphenyl]-2-carboxylate as a crude residue (interm. 44). Example 12

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - US5461050, 1995, A
[2]Current Patent Assignee: JOHNSON & JOHNSON INC - US5468743, 1995, A

40
ethylenediaminetetracetic acid [ No CAS ]
[ 106-38-7 ]
[ 610-97-9 ]
[ 114772-34-8 ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium In tetrahydrofuran; hexane; chloroform; water	1.i EXAMPLE 1 (i) A 1.6M solution of butyllithium in hexane (24.4 ml) was added dropwise to a stirred solution of 4-bromotoluene (6.0 g) in dry tetrahydrofuran (THF, 50 ml) at -78° C. under an atmosphere of argon. The temperature was maintained at -78° C. for 20 minutes, and then a 1M solution of anhydrous zinc chloride in ether (38.6 ml) was added. The solution was kept at -78° C. for 15 minutes and then tetrakis(triphenylphosphine)palladium (60 mg) in THF (5 ml) was added, followed by methyl 2-iodobenzoate (6.1 g) in THF (10 ml). The solution was allowed to reach ambient temperature over 1 hour, then heated under reflux for 5 hours. The solvent was removed by evaporation and the residue was dissolved in chloroform (150 ml). The solution washed with a solution of ethylenediaminetetracetic acid (10 g) in water (100 ml) and the aqueous layer was re-extracted with chloroform (100 ml). The combined organic extracts were dried (MgSO4) and the solvent removed by evaporation. The residue was purified by flash chromatography, eluding with ethyl acetate/hexane (1:9 v/v), to give methyl 4'-methylbiphenyl-2-carboxylate (B) as a colourless oil (4.4 g); NMR (CDCl3): 2.4(s,3H), 3.65(s,3H), 7.2(s,4H, 7.35(m,3H), 7.35(m,3H), 7.5(m,1H), 7.8(d,1H).
	With n-butyllithium In tetrahydrofuran; hexane; chloroform; water	35.i EXAMPLE 35 (i) A 1.6M solution of butyllithium in hexane (24.0 ml) was added dropwise to a stirred solution of 4-bromotoluene (6.0 g) in dry THF (50 ml) at -78° C. under an atmosphere of argon. The temperature was maintained at -78° C. for 20 minutes and then a 1M solution of anhydrous zinc chloride in ether (38.6 ml) was added. The solution was kept at -78° C. for 15 minutes, and then tetrakis(triphenylphosphine)palladium (60 mg) in THF (5 ml) was added, followed by methyl 2-iodobenzoate (6.1 g) in THF (10 ml). The solution was allowed to reach ambient temperature over 1 hour, then heated under reflux for 5 hours. The solvent was removed by evaporation and the residue was dissolved in chloroform (150 ml). The solution was washed with a solution of ethylenediaminetetracetic acid (10 g) in water (100 ml) and the aqueous layer was re-extracted with chloroform (100 ml). The combined organic extracts were dried (MgSO4) and the solvent removed by evaporation. The residue was purified by flash chromatography, eluding with ethyl acetate/hexane (1:9 v/v), to give methyl 4'-methylbiphenyl-2-carboxylate (B) as a colourless oil (4.4 g); NMR: 2.4(s,3H), 3.65(s,3H), 7.2(s,4H), 7.35(m,3H), 7.5(m,1H), 7.8(d,1H).

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - US5171748, 1992, A
[2]Current Patent Assignee: ASTRAZENECA PLC - US5130318, 1992, A

41
[ 7148-03-0 ]
[ 75-36-5 ]
[ 114772-34-8 ]

Yield	Reaction Conditions	Operation in experiment
	In methanol	85 Preparation of methyl 4'-methylbiphenyl-2-carboxylate Preparation of methyl 4'-methylbiphenyl-2-carboxylate To 100 mL of methanol was added dropwise 5 mL of acetyl chloride with ice cooling. After stirring the mixture for 15 minutes, 5 g of the acid from Step 4 was added at once and the mixture was refluxed for 4 hours. The reaction mixture was concentrated to remove the solvent and the desired methyl ester was obtained as a thick liquid, 5 g.
	In methanol	85 Preparation of methyl 4'-methylbiphenyl-2-carboxylate Preparation of methyl 4'-methylbiphenyl-2-carboxylate To 100 mL of methanol was added dropwise 5 mL of acetyl chloride with ice cooling. After stirring the mixture of 15 minutes, 5 g of the acid from Step 4 was added at once and the mixture was refluxed for 4 hours. The reaction mixture was concentrated to remove the solvent and the desired methyl ester was obtained as a thick liquid, 5 g.

Reference： [1]Current Patent Assignee: DUPONT DE NEMOURS INC - US5138069, 1992, A
[2]Current Patent Assignee: DUPONT DE NEMOURS INC - US5128355, 1992, A

42
ethylenediamine Tetraacetic Acid [ No CAS ]
[ 106-38-7 ]
[ 610-97-9 ]
[ 114772-34-8 ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium In tetrahydrofuran; hexane; chloroform; water	1.1 EXAMPLE 1 (1) A 1.6M solution of butyllithium in hexane (24.0 ml) was added dropwise to a stirred solution of 4-bromotoluene (6.0 g) in dry tetrahydrofuran (THF) (50 ml) at -78° C. under an atmosphere of argon. The temperature was maintained at -78° C. for 20 minutes and then a 1M solution of anhydrous zinc chloride in ether (38.6 ml) was added. The solution was kept at -78° C. for 15 minutes, and then tetrakis(triphenylphosphine)palladium (60 mg) in THF (5 ml) was added, followed by methyl 2-iodobenzoate (6.1 g) in THF (10 ml). The solution was allowed to reach ambient temperature over 1 hour, then heated under reflux for 5 hours. The solvent was removed by evaporation and the residue was dissolved in chloroform (150 ml). The solution was washed with a solution of ethylenediamine tetracetic acid (10 g) in water (100 ml) and the aqueous layer was re-extracted with chloroform (100 ml). The combined organic extracts were dried (MgSO4) and the solvent removed by evaporation. The residue was purified by flash chromatography, eluding with ethyl acetate/hexane(1:9 v/v) to give methyl 4'methylbiphenyl-2-carboxylate (B1) as a colourless oil (4.4 g); NMR: 2.4(s,3H), 3.65(s,3H), 7.2(s,4H), 7.35(m,3H), 7.5(m,1H), 7.8(d,1H).

Reference： [1]Current Patent Assignee: AKZO NOBEL NV - US5126344, 1992, A

43
[ 114772-34-8 ]
[ 143573-45-9 ]

Yield	Reaction Conditions	Operation in experiment
17.9 g (85%)	In ethanol	1.1 Step 1: Step 1: Preparation of 4'-cyanomethylbiphenyl-2-carboxylate Under nitrogen, a sodium ethoxide solution was prepared by reacting 4.05 g (176 mmol) of metallic sodium with 400 mL of absolute ethanol. A 20.0 g (88 mmol) sample of methyl 4'-methylbiphenyl-2-carboxylate (Chemo Dynamics Inc.) was added and the reaction was allowed to stir at reflux for 5 days. The reaction was concentrated in vacuo and partitioned between water and ether. The organic layer was dried (MgSO4) and reconcentrated in vacuo to give 17.9 g (85%) of ethyl 4'-methylbiphenyl-2-carboxylate (4 in Scheme I): NMR (CDCl3) δ 1.06 (t, J=7Hz, 3H), 2.52 (s, 3H), 4.14 (q, J=7 Hz, 2H), 7.18-7.27 (m, 4H), 7.35-7.44 (m, 2H), 7.48-7.56 (m, 1H), 7.83 (d, J=8Hz, 1H).

Reference： [1]Current Patent Assignee: PFIZER INC - US5140036, 1992, A

44
[ 7148-03-0 ]
[ 74-88-4 ]
[ 114772-34-8 ]

Yield	Reaction Conditions	Operation in experiment
96%	Stage #1: o-tolylbenzoic acid With potassium carbonate In acetone for 0.25h; Stage #2: methyl iodide In acetone for 24h; Reflux;

Reference： [1]Location in patent: experimental part Catalano, Alessia; Carocci, Alessia; Di Mola, Antonia; Bruno, Claudio; Vanderheyden, Patrick M. L.; Franchini, Carlo [Archiv der Pharmazie, 2011, vol. 344, # 9, p. 617 - 626]

45
[ 610-97-9 ]
[ 31614-66-1 ]
[ 114772-34-8 ]

Yield	Reaction Conditions	Operation in experiment
86%	With bis-triphenylphosphine-palladium(II) chloride; lithium chloride In N,N-dimethyl-formamide Inert atmosphere;

Reference： [1]Sánchez, Ana I.; Martínez-Barrasa, Valentín; Burgos, Carolina; Vaquero, Juan J.; Alvarez-Builla, Julio; Terricabras, Emma; Segarra, Víctor [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 8, p. 2370 - 2378]

46
[ 114772-34-8 ]
C₁₅H₁₂Br₂O₂ [ No CAS ]
[ 114772-38-2 ]

Yield	Reaction Conditions	Operation in experiment
92.6%	With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; 2,2'-azobis(isobutyronitrile) In chloroform at 60 - 65℃;

Reference： [1]Reddy, Kikkuru Srirami; Srinivasan, Neti; Reddy, Chinta Raveendra; Kolla, Naveenkumar; Anjaneyulu, Yerremilli; Venkatraman, Sundaram; Bhattacharya, Apurba; Mathad, Vijayavitthal T. [Organic Process Research and Development, 2007, vol. 11, # 1, p. 81 - 85]

47
[ 114772-34-8 ]
[ 144701-48-4 ]

Reference： [1]Organic Process Research and Development,2007,vol. 11,p. 81 - 85
[2]Patent: CN104768936,2017,B
[3]Patent: CN104768936,2017,B

48
[ 114772-34-8 ]
[ 18110-73-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium hydroxide; water / tetrahydrofuran / 80 °C 2: copper(II) acetate monohydrate; tert-Butyl peroxybenzoate / 1,2-dichloro-ethane / 12 h / 20 - 85 °C
	Multi-step reaction with 2 steps 1: sodium hydroxide; water / methanol / 6 h / 50 °C 2: silver nitrate; potassium acetate; ammonium peroxydisulfate / dichloromethane; water / 24 h / 20 °C
	Multi-step reaction with 2 steps 1: sodium hydroxide; water / methanol / 12 h / 50 °C / Inert atmosphere 2: 9-(2-mesityl)-10-methylacridinium perchlorate; ammonium peroxydisulfate / water; 1,2-dichloro-ethane / 14 h / 20 - 35 °C / Irradiation

Multi-step reaction with 2 steps 1: potassium hydroxide / methanol / 80 °C 2: 2,3-dicyano-5,6-dichloro-p-benzoquinone; tert.-butylnitrite; oxygen / 1,2-dichloro-ethane / 8 h / 20 °C / 750.08 Torr / Irradiation; Sealed tube; Green chemistry

Reference： [1]Wang, Yang; Gulevich, Anton V.; Gevorgyan, Vladimir [Chemistry - A European Journal, 2013, vol. 19, # 47, p. 15836 - 15840]
[2]Dai, Jian-Jun; Xu, Wen-Tao; Wu, Ya-Dong; Zhang, Wen-Man; Gong, Ying; He, Xia-Ping; Zhang, Xin-Qing; Xu, Hua-Jian [Journal of Organic Chemistry, 2015, vol. 80, # 2, p. 911 - 919]
[3]Ramirez, Nieves P.; Bosque, Irene; Gonzalez-Gomez, Jose C. [Organic Letters, 2015, vol. 17, # 18, p. 4550 - 4553]
[4]Chen, Bajin; Hu, Baoxiang; Hu, Xinquan; Jin, Liqun; Li, Meichao; Shen, Zhenlu; Sun, Nan; Wang, Shengpeng; Wang, Yiqing [Synlett, 2020, vol. 31, # 3, p. 261 - 266]

49
[ 394-35-4 ]
[ 90252-89-4 ]
[ 114772-34-8 ]

Yield	Reaction Conditions	Operation in experiment
86%	Stage #1: methyl 2-fluorobenzoate; p-tolylzinc(II) chloride With bis(tricyclohexylphosphine)nickel(II) dichloride In tetrahydrofuran; 1-methyl-pyrrolidin-2-one at 25 - 100℃; for 10h; Schlenk technique; Inert atmosphere; Stage #2: p-tolylzinc(II) chloride In tetrahydrofuran; 1-methyl-pyrrolidin-2-one at 100℃; for 10h; Inert atmosphere; Schlenk technique;

Reference： [1]Zhu, Feng; Wang, Zhong-Xia [Journal of Organic Chemistry, 2014, vol. 79, # 10, p. 4285 - 4292]

50
[ 610-97-9 ]
[ 18412-57-2 ]
[ 114772-34-8 ]

Yield	Reaction Conditions	Operation in experiment
88%	With copper(l) iodide; tetrakis(triphenylphosphine) palladium⁽⁰⁾; tetrabutyl ammonium fluoride In tetrahydrofuran; water at 80℃; for 40h;

Reference： [1]Traficante, Carla I.; Mata, Ernesto G.; Delpiccolo, Carina M. L. [RSC Advances, 2015, vol. 5, # 34, p. 26796 - 26800]

51
methyl 2-((N,N-dimethylsulfamoyl)oxy)benzoate [ No CAS ]
[ 90252-89-4 ]
[ 114772-34-8 ]

Yield	Reaction Conditions	Operation in experiment
62%	With 1-Methylpyrrolidine; C₂₀H₂₀ClN₃Ni In tetrahydrofuran at 50℃; for 12h; Schlenk technique; Inert atmosphere;

Reference： [1]Tao, Jian-Long; Wang, Zhong-Xia [European Journal of Organic Chemistry, 2015, vol. 2015, # 29, p. 6534 - 6540]

52
[ 610-96-8 ]
[ 380481-66-3 ]
[ 114772-34-8 ]

Yield	Reaction Conditions	Operation in experiment
94%	With potassium phosphate tribasic hydrate; NiIICl(1-naphthyl)(tricyclohexylphosphine)2; tricyclohexylphosphine; In tetrahydrofuran; at 23℃; for 4h;Inert atmosphere; Glovebox; Sealed tube;	General procedure: Cross-Coupling of ortho-, meta-, and para-Substituted, Electron-Rich and Electron-Deficient Aryl Halides and Aryl Mesylates with Aryl Neopentylglycolboronates Catalyzed by NiIICl(1-naph-thyl)(PCy3)2/PCy3 in Anhydrous THF at 23 C; General Procedure 2In an oven-dried test tube charged with a Teflon coated stirring barwere added aryl halide or aryl mesylate (0.3 mmol), aryl neopentyl-glycolboronates (0.315 mmol), K3PO4(H2O)3.2 (191.00 ± 1.00 mg, 0.9mmol), and NiIICl(1-naphthyl)(PCy3)2 (11.73 ± 0.0510 mg, 0.015mmol, 5% catalyst loading). The test tube was brought into a N2 filledglove box (moisture level <2 ppm) through three degassing cycles andPCy3 (8.4 mg, 0.03 mmol, 10% loading) ligand was added. Distilled sol-vent (1 mL) was added inside the glove box and the test tube wassealed by a rubber septum and left stirring at 23 C. A sample was tak-en by syringe and transferred outside the glove box. The sample wasdiluted by distilled THF (0.2 mL) and filtered through a short columnof Al2O3. The filtrate was concentrated and the GC analysis was car-ried out. The reaction mixture was diluted with CH2Cl2 (2 mL), filteredthrough a layer of Al2O3, and washed with CH2Cl2 (3 1 mL). The fil-trate was collected and concentrated under vacuum. The crude prod-uct was purified by column chromatography on silica gel with EtO-Ac/hexane mixture as eluent. The reductive elimination side-productwas also isolated and characterized.

Reference： [1]Synthesis,2016,vol. 48,p. 2795 - 2807

53
[ 114772-34-8 ]
4'-chloromethylbiphenyl-2-carboxylic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21 g	With tert.-butylhydroperoxide; thionyl chloride In dichloromethane at 20 - 30℃; for 1.5h;	10 Preparation of 4'-chloromethylbiphenyl-2-carboxylate(II, R = COOCH3, X = Cl) In a 250 ml three-necked flask with a drying tube,4'-methylbiphenyl 2-carboxylate (IV) (22.6 g, 0.1 mol) was added,Dichloromethane (44 mL) was dissolved with stirring. Water bath control temperature 20-30°C ,While slowly adding 65% tert-butoxy hydroperoxide (4.7 g, 0.5 eq)And sulfonyl chloride (19 g, 1.4 eq), exotherm, a large amount of acid gas released,About 30 minutes after the drop finished, 1 hour after sampling,HPLC detection of less than 5% of raw materials, diluted with dichloromethane (10ml),Add saturated sodium sulfite wash, sodium carbonate solution adjusted PH 6-7,Washed 3 times, dried, filtered,Concentrated under reduced pressure to remove dichloromethane to give 24 g of a yellow oil,Add anhydrous ethanol (30ml) stirring, ice bath cooling, precipitation of large amounts of white solid,A white solid (II, R = COOCH3) was removed by filtration to give 23.4 g,HPLC analysis of 95% purity, ethanol (40mL) recrystallization,The product was 21 g and the liquid purity was 98.2%.

Reference： [1]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES; Shanghai Institute of Materia Medica (in: CAS); TOPHARMAN SHANGHAI CO., LTD. - CN104768936, 2017, B Location in patent: Paragraph 0120-0121

54
[ 114772-34-8 ]
[ 152620-34-3 ]

Yield	Reaction Conditions	Operation in experiment
80.5%	With sulfuric acid; sodium bromide In dichloromethane; water at 25℃;	6 [0065] The production method of an explicit 2-R-4-bromomethyl-biphenyl is present, wherein R is methoxycarbonyl, the method provides material: 2_ methoxycarbonyl-4'-methylbiphenyl, bromo sodium, sodium bromide, concentrated sulfuric acid, water and a first organic solvent; wherein the molar ratio of sodium bromate and 2-methoxycarbonyl-biphenyl-4'0.204: 1; sodium bromide with 2- molar ratio of methyl 4'-methoxycarbonyl-biphenyl is 0.95: 1; molar ratio of concentrated sulfuric acid 2-methoxycarbonyl-4-methyl-biphenyl was 0.59: 1; a first organic solvent methoxy 2_ _4'_ weight ratio of carbonyl-biphenyl volume of 6: lml / g; water as a solvent and 2-methoxycarbonyl-4'-methylbiphenyl-volume ratio by weight of 8: lml / g; with dilution volume of concentrated sulfuric acid and concentrated sulfuric acid by weight of water ratio of 7: lml / g, the first organic solvent is methylene chloride. 2_-4'-117g(517.1mmolleq)16g(106.0mmol0.204eq)50.5g(490.8mmol0.95eq)30g (305.8mmol0.59eq)702ml936ml210ml Specific amounts of raw materials was added as follows: 2_ methoxycarbonyl-4'-methyl-biphenyl 117g (517.1mmol, leq), sodium bromate 16g (106.0mmol, 0.204eq), sodium bromide 50.5g (490.8mmol, 0.95 EQ), concentrated sulfuric acid 30g (305.8mmol, 0.59eq), 702 mL dichloromethane, 936ml water as a solvent, concentrated sulfuric acid for dilution water 210ml [0066] 2S1100:2--4'-25°C 25°ClOh;S1200:;S1300:700ml/S13002--4 127g80.5 % [0066] According to the preparation process of the flowchart shown in FIG. 2, first enter bromo Step S1100: The 2-methoxycarbonyl-4'-methylbiphenyl, sodium bromate, sodium bromide, and methylene chloride water as a solvent added to the reactor and stirred uniformly at 25 ° C diluted with water and concentrated sulfuric acid was added dropwise to the stirred reactor, the reaction system was maintained at 25 ° C the reaction product is brominated to give a reaction solution lOh; after entering the processing step S1200: the brominated product of the reaction solution was separated, and the aqueous phase was extracted with dichloromethane, the organic phases were combined, dried and concentrated to give a pale yellow solid; the last to enter the recrystallization step S1300: the crude material was added 700ml of petroleum ether / isopropyl ether mixed solution was heated to reflux for natural cooling after recrystallization completely dissolved; step S1300 to this end, the preparation of 2-methoxycarbonyl-4-bromomethyl-biphenyl is completed, to give 127g white solid, a yield of 80.5%.

Reference： [1]Current Patent Assignee: BEIJING SINEVA TECHNOLOGY CO LTD - CN104744303, 2017, B Location in patent: Paragraph 0065; 0066

55
(S,Z)-1-(2-bromophenyl)-3-iodo-3-(trimethylsilyl)prop-2-en-1-ol [ No CAS ]
[ 114772-34-8 ]
(Ra)-(1-(4'-methyl-[1,1'-biphenyl]-2-yl)naphthalen-2-yl)trimethylsilane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	Stage #1: (S,Z)-1-(2-bromophenyl)-3-iodo-3-(trimethylsilyl)prop-2-en-1-ol With isopropylmagnesium chloride; magnesium; lithium chloride In diethyl ether at 40℃; for 0.75h; Inert atmosphere; Stage #2: methyl 4'-methylbiphenyl-2-carboxylate In diethyl ether at 20℃; for 1h; Inert atmosphere; Stage #3: With titanium tetra-n-propoxide In tetrahydrofuran; diethyl ether at 20℃; for 3h; Inert atmosphere; stereoselective reaction;

Reference： [1]Link, Achim; Sparr, Christof [Angewandte Chemie - International Edition, 2018, vol. 57, # 24, p. 7136 - 7139][Angew. Chem., 2018, vol. 130, # 24, p. 7254 - 7257,4]

56
methyl 2-(((4-methylphenyl)sulfonamido)methyl)benzoate [ No CAS ]
[ 114772-34-8 ]

Yield	Reaction Conditions	Operation in experiment
9.2 mg	In methanol at 20℃; Inert atmosphere; Schlenk technique; UV-irradiation;
9.2 mg	In methanol at 20℃; UV-irradiation; Inert atmosphere; Schlenk technique;	27.b b. Preparation of methyl 4 '-methyl- [l,l'-biphenyl]-2-carboxylate A solution of methyl 2-(((4-methylphenyl)sulfonamido)methyl)benzoate (19.9 mg, 62.3 prnol) in MeOH (10 mL) was loaded on the photo reactor with a flow rate of 2 mL/min (MeOH) and irradiated with UV light at room temperature. The solvent fraction containing the photoproducts was collected and the solvent was removed under vacuum. The residue was purified by open column chromatography to yield the title compound (9.2 mg, 40.7 pmol, 65%).1H NMR (500 MHz; CDCl3): 5 = 2.40 (s, 3H, -C(CH3)), 3.66 (s, 3H, -OCH3), 7.21 (s, 4H, Me-C-CH-CH-), 7.38 (m, 2H, -C(COOMe)-C-CH-CH-CH-), 7.51 (t, 1H, 3JHH = 7.7 Hz, -C(COOMe)-C-CH-CH-), 7.80 (d, 1H, 3JHH = 1.1 Hz, -C(COOMe)-CH-) ppm. 13C NMR (125.8 MHZ; CDCl3): 5 = 21.4 (1C, -C(CH3)-), 52.1 (1C, -OCH3), 127.1 (1C, -C(COOMe)-C-CH-), 128.4 (2C, -C(CH3)-CH-), 129.0 (2C, -C(CH3)-CH-CH-), 129.9 (1C, -C(COOMe)-CH-), 130.9 (1C, -C(COOMe)-CH-CH-), 131.0 (1C, -C(COOMe)-), 131.3 (1C, -C(COOMe)-C-CH-CH-), 137.1 (1C, -C(CH3)-), 138.5 (1C, -C-C-C(COOMe)-), 142.6 (1C, -C-C(COOMe)-), 169.4 (1C, -CO-) ppm. HRMS (ESI+) calcd. for CI 5HI 502+: 227.1067; found: 227.1069.
	at 20℃; Inert atmosphere; Schlenk technique; UV-irradiation;

Reference： [1]Kloss, Florian; Neuwirth, Toni; Haensch, Veit G.; Hertweck, Christian [Angewandte Chemie - International Edition, 2018, vol. 57, # 44, p. 14476 - 14481][Angew. Chem., 2018, vol. 130, p. 14684 - 14689,6]
[2]Current Patent Assignee: Leibniz Association - WO2019/101679, 2019, A1 Location in patent: Page/Page column 39; 45; 46
[3]Haensch, Veit G.; Neuwirth, Toni; Steinmetzer, Johannes; Kloss, Florian; Beckert, Rainer; Gräfe, Stefanie; Kupfer, Stephan; Hertweck, Christian [Chemistry - A European Journal, 2019, vol. 25, # 70, p. 16068 - 16073]

57
[ 849020-92-4 ]
[ 114772-34-8 ]

Reference： [1]Angewandte Chemie - International Edition,2018,vol. 57,p. 14476 - 14481
Angew. Chem.,2018,vol. 130,p. 14684 - 14689,6

58
[ 114772-34-8 ]
methyl 4'-cyano-[1,1'-biphenyl]-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With hydroxylamine hydrochloride; 2,4,6-triphenylpyrylium tetrafluoroborate; oxygen; ammonium bromide In acetonitrile at 40℃; for 24h; Molecular sieve; Irradiation;

Reference： [1]Murugesan, Kathiravan; Donabauer, Karsten; König, Burkhard [Angewandte Chemie - International Edition, 2021, vol. 60, # 5, p. 2439 - 2445][Angewandte Chemie, 2020, vol. 133, # 5, p. 2469 - 2475,7]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	114772-34-8	MDL No. :	MFCD03453661
Formula :	C₁₅H₁₄O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	IHNIAWHITVGYJJ-UHFFFAOYSA-N
M.W :	226.27 g/mol	Pubchem ID :	1393873
Synonyms :

Num. heavy atoms :	17
Num. arom. heavy atoms :	12
Fraction Csp3 :	0.13
Num. rotatable bonds :	3
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	68.12
TPSA :	26.3 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-4.57 cm/s

Log Po/w (iLOGP) :	2.76
Log Po/w (XLOGP3) :	4.38
Log Po/w (WLOGP) :	3.45
Log Po/w (MLOGP) :	3.67
Log Po/w (SILICOS-IT) :	3.91
Consensus Log Po/w :	3.63

[ CAS No. 114772-34-8 ]

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[ 114772-34-8 ] Synthesis Path-Upstream 1~2

[ 114772-34-8 ] Synthesis Path-Downstream 1~58

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[ 114772-34-8 ]

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

Log S (ESOL) :	-4.33
Solubility :	0.0107 mg/ml ; 0.0000471 mol/l
Class :	Moderately soluble
Log S (Ali) :	-4.65
Solubility :	0.00508 mg/ml ; 0.0000225 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-5.38
Solubility :	0.000932 mg/ml ; 0.00000412 mol/l
Class :	Moderately soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	1.97

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

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. 114772-34-8 ]

Quality Control of [ 114772-34-8 ]

Related Doc. of [ 114772-34-8 ]

Product Details of [ 114772-34-8 ]

Calculated chemistry of [ 114772-34-8 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 114772-34-8 ]

Application In Synthesis of [ 114772-34-8 ]

[ 114772-34-8 ] Synthesis Path-Upstream 1~2

[ 114772-34-8 ] Synthesis Path-Downstream 1~58

Related Functional Groups of [ 114772-34-8 ]

Aryls

Esters

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 114772-34-8 ]