[ CAS No. 6317-89-1 ]

Name: 6317-89-1|3-Acetamidophenyl acetate|98%
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Product Details of [ 6317-89-1 ]

CAS No. :	6317-89-1	MDL No. :	MFCD00465580
Formula :	C₁₀H₁₁NO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ONWKGGFEPJUBHK-UHFFFAOYSA-N
M.W :	193.20	Pubchem ID :	231988
Synonyms :

Safety of [ 6317-89-1 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P501-P261-P270-P271-P264-P280-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330-P302+P352+P312-P304+P340+P312	UN#:	N/A
Hazard Statements:	H302+H312+H332-H315-H319	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 6317-89-1 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 6317-89-1 ]
Downstream synthetic route of [ 6317-89-1 ]

[ 6317-89-1 ] Synthesis Path-Upstream 1~4

1
[ 6317-89-1 ]
[ 2476-29-1 ]

Reference： [1] Bulletin de la Societe Chimique de France, 1952, p. 639
[2] Journal of Medicinal Chemistry, 2013, vol. 56, # 15, p. 6033 - 6053

2
[ 6317-89-1 ]
[ 16292-88-9 ]

Reference： [1] Patent: US2012/15962, 2012, A1,

3
[ 6317-89-1 ]
[ 40547-58-8 ]

Yield	Reaction Conditions	Operation in experiment
73%	Stage #1: at 75 - 95℃; Cautiously heating Stage #2: at 20℃;	3-Acetamidophenyl acetate (10.47 g, 54.19 MMOL) WAS ground to a fine powder in a pestle and mortar, then mixed with AIC13 (14.45 g, 108.40 MMOL) in a 250 mL round-bottomed flask equiped with a BUBBLER attached to a nitrogen supply. The mixture was heated cautiously until melting (75 C) and subsequent vigourous reaction (85 C) had occurred (CAUTION : Vigourous exothermic reaction with evolution of gas. Note: The temperature at which these processes occurs shows some variation-the temperature indicated are the lowest observed, and the highest are approximately 30 C higher for each process). The mixture was cooled to room temperature and the brown solid broken to a powder with a spatula. The mixture was then heated at 180 C for 4.25 hours, and cooled to room temperature. The solid mass was broken up with a spatula, and ice-water (100 mL) was added. The mixture was stirred vigourously overnight and the pure product removed by filtration. The product was dried at reduced pressure (45 C, 100 mbar) for 18 hours to give N- (4- acetyl-3-hydroxy-phenyl)-acetamide (7.66g, 73percent) as an off-white powder; (DMSO-D6) 12.32 (1 H, s), 10.28 (1 H, s), 7.83 (1 H, d, J = 8.8 Hz), 7.35 (1 H, d, J = 2.0 Hz), 7.05 (1 H, dd, J = 8.8, 2.0 Hz), 2.56 (3H, s), 2.07 (3H, s); LCMS retention time 1.87 min, M+H 194. 2.

Reference： [1] Patent: WO2004/56782, 2004, A1, . Location in patent: Page 44-45
[2] Journal of Medicinal Chemistry, 2013, vol. 56, # 15, p. 6033 - 6053
[3] Pharmacy and Pharmacology Communications, 1999, vol. 5, # 5, p. 323 - 329
[4] Nippon Kagaku Zasshi, 1955, vol. 76, p. 535,536[5] Chem.Abstr., 1957, p. 17902
[6] Bulletin de la Societe Chimique de France, 1952, p. 639
[7] Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 21, p. 5996 - 6001
[8] Patent: US2007/117823, 2007, A1, . Location in patent: Page/Page column 8
[9] Patent: WO2007/54580, 2007, A1, . Location in patent: Page/Page column 15-16
[10] Journal of Medicinal Chemistry, 2009, vol. 52, # 12, p. 3703 - 3715

4
[ 6317-89-1 ]
[ 60207-18-3 ]

Reference： [1] Bulletin de la Societe Chimique de France, 1952, p. 639
[2] Bulletin de la Societe Chimique de France, 1952, p. 639
[3] Journal of Medicinal Chemistry, 2013, vol. 56, # 15, p. 6033 - 6053

[ 6317-89-1 ] Synthesis Path-Downstream 1~51

1
[ 6317-89-1 ]
[ 712-34-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 42 percent / nitric acid / 3 h / -15 - -10 °C 2: 98 percent / K₂CO₃, methanol / 5 h / Ambient temperature
	Multi-step reaction with 2 steps 1: nitric acid / 3 h / -15 - -10 °C 2: potassium carbonate / methanol / 3 h / 20 °C

Reference： [1]Meldola; Hollely [Journal of the Chemical Society, 1914, vol. 105, p. 987] Reverdin [Chemische Berichte, 1914, vol. 47, p. 2217]
[2]Sundberg; Baxter; Pitts; Ahmed-Schofield; Nishiguchi [Journal of Organic Chemistry, 1988, vol. 53, # 21, p. 5097 - 5107]
[3]Current Patent Assignee: ROCHE HOLDING AG - US2012/15962, 2012, A1

2
[ 6317-89-1 ]
[ 40547-58-8 ]

Yield	Reaction Conditions	Operation in experiment
73%		3-Acetamidophenyl acetate (10.47 g, 54.19 MMOL) WAS ground to a fine powder in a pestle and mortar, then mixed with AIC13 (14.45 g, 108.40 MMOL) in a 250 mL round-bottomed flask equiped with a BUBBLER attached to a nitrogen supply. The mixture was heated cautiously until melting (75 C) and subsequent vigourous reaction (85 C) had occurred (CAUTION : Vigourous exothermic reaction with evolution of gas. Note: The temperature at which these processes occurs shows some variation-the temperature indicated are the lowest observed, and the highest are approximately 30 C higher for each process). The mixture was cooled to room temperature and the brown solid broken to a powder with a spatula. The mixture was then heated at 180 C for 4.25 hours, and cooled to room temperature. The solid mass was broken up with a spatula, and ice-water (100 mL) was added. The mixture was stirred vigourously overnight and the pure product removed by filtration. The product was dried at reduced pressure (45 C, 100 mbar) for 18 hours to give N- (4- acetyl-3-hydroxy-phenyl)-acetamide (7.66g, 73%) as an off-white powder; (DMSO-D6) 12.32 (1 H, s), 10.28 (1 H, s), 7.83 (1 H, d, J = 8.8 Hz), 7.35 (1 H, d, J = 2.0 Hz), 7.05 (1 H, dd, J = 8.8, 2.0 Hz), 2.56 (3H, s), 2.07 (3H, s); LCMS retention time 1.87 min, M+H 194. 2.
	aluminum (III) chloride; at 170 - 180℃; for 8h;	Fries migration was carried out with this compound by heating with anhydrous aluminum chloride at 170-180 C. for 8 hours to obtain the acetophenone derivative, which was hydrolyzed without isolation by refluxing in 2N HCl to obtain the product Vd in 60% yield.
	aluminum (III) chloride; at 170 - 180℃; for 8h;	4. 4-amino-2-hydroxyacetophenone was obtained through the pathway given below. 3-Aminophenol is used as the raw material and condensed with acetic anhydride in the presence of pyridine to get the diacetyl derivative in 80% yield. Fries migration was carried out with this compound by heating with anhydrous aluminium chloride at 170-180 0C for 8 h to get the acetophenone derivative which was hydrolyzed without isolation by refluxing in 2N HCI to get the product Vd in 60% yield <n="17"/>H3O

Reference： [1]Patent: WO2004/56782,2004,A1 .Location in patent: Page 44-45
[2]Journal of Medicinal Chemistry,2013,vol. 56,p. 6033 - 6053
[3]Pharmacy and Pharmacology Communications,1999,vol. 5,p. 323 - 329
[4]Nippon Kagaku Zasshi,1955,vol. 76,p. 535,536
Chem.Abstr.,1957,p. 17902
[5]Bioorganic and Medicinal Chemistry,2005,vol. 13,p. 5996 - 6001
[6]Patent: US2007/117823,2007,A1 .Location in patent: Page/Page column 8
[7]Patent: WO2007/54580,2007,A1 .Location in patent: Page/Page column 15-16
[8]Journal of Medicinal Chemistry,2009,vol. 52,p. 3703 - 3715

3
[ 6317-89-1 ]
[ 621-42-1 ]

Yield	Reaction Conditions	Operation in experiment
80%	In water at 25℃; trypsin, O_.1 M phosphate buffer, pH 8.0;
	With aluminium-chloride-diisopropylate; aluminum isopropoxide
	Stage #1: 3-acetamidophenyl acetate With water; sodium hydrogencarbonate In methanol for 1h; Heating / reflux; Stage #2: With hydrogenchloride In water Acidic aqueous solution;	1 To a stirred mixture of 3-aminophenol (10 g, 91 mmol) and ZnO (8 g) was added acetic anhydride (10 mL, 92 mmol). The reaction mixture was stirred at room temperature for 15 min, dissolved in acetone (50 mL), the precipitate was filtered off, the filtrate was washed with acetone, and the solvent was evaporated in vacuo. The diacyl compound was dissolved in MeOH (130 mL) and after adding saturated solution of NaHCO3 the mixture was heated under reflux for 1 h. The solvent was evaporated in vacuo, the residue was acidified with HCl, and then extracted with EtOAc. The organic solution was dried and evaporation of solvent afforded crude monoacetylated compound (12.7 g) which was recrystallized from a mixture of CH2Cl2 - MeOH (20:1). The precipitate was filtered and washed with CH2Cl2 - MeOH until a white solid. Yield: 11.5 g (83.6%); Rf= 0.6 (CH2Cl2 - MeOH 9:1).

Stage #1: 3-acetamidophenyl acetate With water; sodium hydrogencarbonate In methanol for 1h; Heating / reflux; Stage #2: With hydrogenchloride In water

1 To a stirred mixture of 3-aminophenol (10 g, 91 mmol) and ZnO (8 g) was added acetic anhydride (10 mL, 92 mmol). The reaction mixture was stirred at room temperature for 15 min, dissolved in acetone (50 mL), the precipitate was filtered off, the filtrate was washed with acetone, and the solvent was evaporated in vacuo. The diacyl compound was dissolved in MeOH (130 mL) and after adding saturated solution of NaHCO3 the mixture was heated under reflux for 1 h. The solvent was evaporated in vacuo, the residue was acidified with HCl, and then extracted with EtOAc. The organic solution was dried and evaporation of solvent afforded crude monoacetylated compound (12.7 g) which was recrystallized from a mixture of CH2Cl2-MeOH (20:1). The precipitate was filtered and washed with CH2Cl2-MeOH until a white solid.Yield: 11.5 g (83.6%); Rt 0.6 (CH2Cl2-MeOH 9:1).

Reference： [1]Parmar, V S; Prasad, A K; Tyagi, O D; Gupta, Sandhya; Sinha, Rita; et al. [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1992, vol. 31, # 12, p. 903 - 905]
[2]Gal; Krasznai [Acta Chimica Academiae Scientiarum Hungaricae, 1958, vol. 17, p. 171,176]
[3]Current Patent Assignee: Corporacion Quimico Farmaceutica Esteve SA - EP2016943, 2009, A1 Location in patent: Page/Page column 18-19
[4]Current Patent Assignee: Corporacion Quimico Farmaceutica Esteve SA - US2009/30013, 2009, A1 Location in patent: Page/Page column 10

4
[ 108-24-7 ]
[ 591-27-5 ]
[ 6317-89-1 ]

Yield	Reaction Conditions	Operation in experiment
96%	With C₃₆H₃₀N₄O₄2C₃H₇NO2NO₃^(1-)Zn⁽²⁺⁾2C₂H₃N In dichloromethane at 20℃; for 36h;
96%	With copper(II) ferrite In neat (no solvent) at 20℃; for 0.75h; Green chemistry;
93%	Stage #1: acetic anhydride; m-Hydroxyaniline With pyridine at 80℃; for 2h; Inert atmosphere; Stage #2: With sodium hydrogencarbonate In water Inert atmosphere;	13; 83 3-aminophenol (19 g, 17 mol) was dissolved in Ac2O (162 g, 1.59 mol, 9.5 eq.), and pyridine (4.9 g, 0.062 mol, 0.36 eq.) was added. Then the reaction mixture was stirred at 80 °C over 2h. Ice water (50 mL) was added to the mixture, and added saturated NaHCO3 solution to the mixture until pH=7, then extracted (ethyl acetate), washed (brine), dried (Na2SO4), concentrated to give 3-acetamidophenyl acetate as gray solid (30 g, yield: 93%). ESI-MS: 194 (M+H)+.

93%	In water at 50℃; for 0.166667h;	A general procedure for acetylation of arylamines with Ac2O/F3O4/Cu MNPs system General procedure: In a round-bottom flask (10 mL) equipped with a magnetic stirrer, a mixture of PhNH2(1 mmol, 0.093 g) and H2O(3 mL) in oil bath (50 °C) was prepared. Magnetically recyclable nanoparticles of Fe3O4/Cu (0.05 mmol) was then added, and the mixture was stirred for 1 min under oil bath conditions. Addition of Ac2O(1 mmol, 0.102 g) to the prepared mixture was followed by stirring for 3 min at 50 °C. After completion of the reaction, the copper nanocatalyst was separated by an external magnet and the mixture was extracted with EtOAc (3 × 8 mL). Organic layers were then dried over anhydrous sodium sulfate. Evaporation of the solvent under reduced pressure affords the pure acetanilide in 95% yield (0.128 g, Table 2, entry 1).
80%	With pyridine	4 3-Aminophenol was used as the raw material and condensed with acetic anhydride in the presence of pyridine to obtain the diacetyl derivative in 80% yield.
80%	With pyridine	4 4. 4-amino-2-hydroxyacetophenone was obtained through the pathway given below. 3-Aminophenol is used as the raw material and condensed with acetic anhydride in the presence of pyridine to get the diacetyl derivative in 80% yield. Fries migration was carried out with this compound by heating with anhydrous aluminium chloride at 170-180 0C for 8 h to get the acetophenone derivative which was hydrolyzed without isolation by refluxing in 2N HCI to get the product Vd in 60% yield H3O
75%	With sodium hydroxide In ethyl acetate at 80℃; for 5h;
	at 150 - 160℃;
	at 20℃; for 1.16667h;
	With zinc(II) oxide	1 Example 1 Preparation of 3-acetylaminophenol To a stirred mixture of 3-aminophenol (10 g, 91 mmol) and ZnO (8 g) was added acetic anhydride (10 mL, 92 mmol). The reaction mixture was stirred at room temperature for 15 min, dissolved in acetone (50 mL), the precipitate was filtered off, the filtrate was washed with acetone, and the solvent was evaporated in vacuo. The diacyl compound was dissolved in MeOH (130 mL) and after adding saturated solution of NaHCO3 the mixture was heated under reflux for 1 h. The solvent was evaporated in vacuo, the residue was acidified with HCl, and then extracted with EtOAc. The organic solution was dried and evaporation of solvent afforded crude monoacetylated compound (12.7 g) which was recrystallized from a mixture of CH2Cl2 - MeOH (20:1). The precipitate was filtered and washed with CH2Cl2 - MeOH until a white solid. Yield: 11.5 g (83.6%); Rf= 0.6 (CH2Cl2 - MeOH 9:1).
	With pyridine at 20℃; for 1.5h; Inert atmosphere;
	With pyridine at 0 - 20℃; for 62h;	29.A Acetic anhydride (53 mL, 572.0 mmol) was slowly added to a mixture of 3-aminophenol (25 g, 225.0 mmol) and 4-dimethylaminopyridine (catalytic quantity) in pyridine (100 mL) at 0° C. and the reaction mixture was stirred at room temperature for 62 hours. Water (1 L) was added and the resulting mixture was extracted with ethyl acetate. The organic extracts were washed with an aqueous solution of hydrochloric acid, a saturated aqueous solution of sodium bicarbonate and water, dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to give 21.79 g of acetic acid 3-acetylamino-phenyl ester as a solid without further purifications. A second batch (2.978 g) of this material crashed out of the aqueous layer upon standing and was collected by filtration.
	In ethanol; water at 70℃; for 0.0166667h;	A general procedure for reductive acetylation of nitroarenes General procedure: In a round-bottom flask (25 mL), a solution of nitrobenzene (0.123 g, 1 mmol) in H2O-EtOH (1.5:0.5 mL) was prepared. Magnetically, nanoparticles of NiFe2O4(at)Cu (0.15 g) were added, and the resulting mixture was stirred for 5 min. Afterward,NaBH4 (0.094 g, 2.5 mmol) was added and the resulting mixture was continued to stirring for 1 min at 70 °C. After reduction of nitrobenzene to aniline (monitored by TLC), Ac2O (0.204 g, 2 mmol) was added and the resulting mixture was stirred for 1 min at 70 °C. The nanocatalyst was separated by an external magnet, and the mixture was extracted with EtOAc (3 × 5 mL). The organic layer was dried over anhydrous Na2SO4. Evaporation of the solvent affords the pure acetanilide in 95% yield (0.128 g, Table 3,entry 1).

Reference： [1]Seth, Saona; Venugopalan, Paloth; Moorthy, Jarugu Narasimha [Chemistry - A European Journal, 2015, vol. 21, # 5, p. 2241 - 2249]
[2]Chutia, Rituparna; Chetia, Bolin [New Journal of Chemistry, 2018, vol. 42, # 18, p. 15200 - 15206]
[3]Current Patent Assignee: BIOGEN IDEC INC. - WO2010/51031, 2010, A1 Location in patent: Page/Page column 29; 58
[4]Shokri, Zahra; Zeynizadeh, Behzad [Journal of the Iranian Chemical Society, 2017, vol. 14, # 11, p. 2467 - 2474]
[5]Current Patent Assignee: ABBVIE INC - US2007/117823, 2007, A1 Location in patent: Page/Page column 8
[6]Current Patent Assignee: ABBVIE INC - WO2007/54580, 2007, A1 Location in patent: Page/Page column 15-16
[7]Hu, Yun; Yang, Yaqi; Yu, Yanjun; Wen, Gesi; Shang, Nana; Zhuang, Wei; Lu, Dihan; Zhou, Binhua; Liang, Baoxia; Yue, Xin; Li, Feng; Du, Jun; Bu, Xianzhang [Journal of Medicinal Chemistry, 2013, vol. 56, # 15, p. 6033 - 6053]
[8]Ikuta [American Chemical Journal, 1893, vol. 15, p. 40]
[9]Bhattacharya, Asish K.; Diallo, Mamadou A.; Ganesh, Krishna N. [Synthetic Communications, 2008, vol. 38, # 10, p. 1518 - 1526]
[10]Current Patent Assignee: Corporacion Quimico Farmaceutica Esteve SA - EP2016943, 2009, A1 Location in patent: Page/Page column 18-19
[11]Location in patent: experimental part Suryadevara, Praveen Kumar; Olepu, Srinivas; Lockman, Jeffrey W.; Ohkanda, Junko; Karimi, Mandana; Verlinde, Christophe L. M. J.; Kraus, James M.; Schoepe, Jan; Van Voorhis, Wesley C.; Hamilton, Andrew D.; Buckner, Frederick S.; Gelb, Michael H. [Journal of Medicinal Chemistry, 2009, vol. 52, # 12, p. 3703 - 3715]
[12]Current Patent Assignee: ROCHE HOLDING AG - US2012/15962, 2012, A1 Location in patent: Page/Page column 78
[13]Zeynizadeh, Behzad; Shokri, Zahra; Mohammadzadeh, Iman [Journal of the Iranian Chemical Society, 2020, vol. 17, # 4, p. 859 - 870]

5
[ 30074-98-7 ]
[ 591-27-5 ]
[ 6317-89-1 ]

Yield	Reaction Conditions	Operation in experiment
91%	In dichloromethane Ambient temperature;

Reference： [1]Effenberger, Franz; Bessey, Eberhard [Chemische Berichte, 1980, vol. 113, # 6, p. 2100 - 2109]

6
[ 6317-89-1 ]
[ 89102-03-4 ]
[ 116911-48-9 ]

Yield	Reaction Conditions	Operation in experiment
42%	With nitric acid at -15 - -10℃; for 3h;
42%	With nitric acid at -15 - -10℃; for 3h; Title compound not separated from byproducts;

Reference： [1]Sundberg; Baxter; Pitts; Ahmed-Schofield; Nishiguchi [Journal of Organic Chemistry, 1988, vol. 53, # 21, p. 5097 - 5107]
[2]Sundberg; Baxter; Pitts; Ahmed-Schofield; Nishiguchi [Journal of Organic Chemistry, 1988, vol. 53, # 21, p. 5097 - 5107]

7
[ 75-36-5 ]
[ 591-27-5 ]
[ 6317-89-1 ]

Yield	Reaction Conditions	Operation in experiment
96%	Stage #1: acetyl chloride; m-Hydroxyaniline With pyridine In dichloromethane at 0℃; for 2.5h; Stage #2: at 0℃; for 1h;	Pyridine (46.32 mL, 45.30 g, 572 MMOL) was added to a stirred suspension of 3-aminophenol (25.0 g, 229 MMOL) in DCM (200 mL), and the mixture cooled to 0 C. A solution of acetyl chloride (14.45 mL, 15.95 G, 203.21 MMOL) in DCM (100 mL) was added dropwise (CAUTION : Exotherm) to the mixture from a pressure-equalising dropping funnel over 2.5 hours, and the mixture stirred for a further 1 hour at 0 C. The mixture was poured into HCI (1.0 M in H20 ; 350 mL) and the layers separated. The aqueous layer was extracted with further DCM (150 mL), and the combined organic layers dried (MGS04) and the solvents removed in vacuo. The crude product was further dried for 18 h at 40 C, 150 mbar to give 3-acetamidophenyl acetate (42. 5G, 96%) as a white solid; $ (CI3) 7.83 (1 H, BR S), 7.45 (1 H, t, J = 2. 0 Hz), 7.23 (1 H, t, J = 8.1 Hz), 7.14-7. 11 (1H, m), 6.78-6. 76 (1 H, m), 2.28 (3H, s), 2.06 (3H, s); LCMS retention time 1.76 min, M+H+ 194.2.
94%	In acetonitrile at 20℃; for 12h;
94%	In acetonitrile at 20℃; for 5.5h;

56.49%	With pyridine In dichloromethane at 5℃;
	With pyridine

Reference： [1]Current Patent Assignee: UNIVERSITY OF LONDON; LIGAND PHARMACEUTICALS INC; CANCER RESEARCH UK - WO2004/56782, 2004, A1 Location in patent: Page 44
[2]Ghosh, Rina; Maiti, Swarupananda; Chakraborty, Arijit [Tetrahedron Letters, 2005, vol. 46, # 1, p. 147 - 151]
[3]Ghosh, Rina; Maiti, Swarupananda; Chakraborty, Arijit [Tetrahedron Letters, 2004, vol. 45, # 36, p. 6775 - 6778]
[4]Akamanchi; Padmawar; Thatte; Rege; Dahanukar [Pharmacy and Pharmacology Communications, 1999, vol. 5, # 5, p. 323 - 329]
[5]Bordet, Alexis; Goclik, Lisa; Leitner, Walter; Walschus, Henrik [Green Chemistry, 2022, vol. 24, # 7, p. 2937 - 2945]

8
[ 6317-89-1 ]
[ 33513-42-7 ]
[ 745830-14-2 ]

Yield	Reaction Conditions	Operation in experiment
22%	With trichlorophosphate at 75℃;
10%	Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; for 0.5h; Inert atmosphere; Stage #2: 3-acetamidophenyl acetate at 0 - 65℃; Inert atmosphere; Stage #3: With sodium hydrogencarbonate In water Inert atmosphere;	13; 84 A three-neck flask was charged with DMF (25 mL, 0.325 mol, 3 eq.), then POCl3 (70 mL, 0.758 mol, 7 eq.) was added to the DMF at 0 °C . The solution was stirred at 0 °C for 30 min. Then 3-acetamidophenyl acetate (20.8 g, 0.108 mol) was added to the mixture at 0 0C . After 30 min the mixture heated to 65 °C and stirred for 16 h. Then, the reaction mixture was added ice water (300 mL) and neutralized with saturated NaHCO3 to pH=6 , extracted (ethyl acetate), washed (brine), dried (Na2SO4), filtered and evaporated to dryness to give the crude product, which was purified by silica gel column chromatography (ethyl acetate:pet. ether, 3: 1) to give 2-chloro-3-formylquinolin-7-yl acetate as gray solid (2.67 g, yield 10%). ESI-MS: 250 (M+H)+. 1H NMR (300 MHz, CDCl3) δ: 2.39 (s, 3H), 7.42-7.45 (m, IH), 7.80-7.81 (d, IH), 7.97-8.00 (d, IH), 8.74 (s, lH), 10.54 (s,lH).

Reference： [1]Sato, Itaru; Nakao, Tomohiko; Sugie, Rie; Kawasaki, Tsuneomi; Soai, Kenso [Synthesis, 2004, # 9, p. 1419 - 1428]
[2]Current Patent Assignee: BIOGEN IDEC INC. - WO2010/51031, 2010, A1 Location in patent: Page/Page column 29-30; 58

9
[ 6317-89-1 ]
[ 89102-04-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 42 percent / nitric acid / 3 h / -15 - -10 °C 2: 98 percent / K₂CO₃, methanol / 5 h / Ambient temperature 3: 98 percent / K₂CO₃, KI / dimethylformamide / 4 h / Ambient temperature

Reference： [1]Sundberg; Baxter; Pitts; Ahmed-Schofield; Nishiguchi [Journal of Organic Chemistry, 1988, vol. 53, # 21, p. 5097 - 5107]

10
[ 6317-89-1 ]
[ 89102-05-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 42 percent / nitric acid / 3 h / -15 - -10 °C 2: 98 percent / K₂CO₃, methanol / 5 h / Ambient temperature 3: 98 percent / K₂CO₃, KI / dimethylformamide / 4 h / Ambient temperature 4: 83 percent / potassium tert-butoxide / dimethylformamide / 24 h / Ambient temperature

Reference： [1]Sundberg; Baxter; Pitts; Ahmed-Schofield; Nishiguchi [Journal of Organic Chemistry, 1988, vol. 53, # 21, p. 5097 - 5107]

11
[ 6317-89-1 ]
[ 116911-49-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: 42 percent / nitric acid / 3 h / -15 - -10 °C 2: 98 percent / K₂CO₃, methanol / 5 h / Ambient temperature 3: 98 percent / K₂CO₃, KI / dimethylformamide / 4 h / Ambient temperature 4: 83 percent / potassium tert-butoxide / dimethylformamide / 24 h / Ambient temperature 5: Zn, CaCl₂, C₂H₅OH, H₂O / 1.5 h / Heating

Reference： [1]Sundberg; Baxter; Pitts; Ahmed-Schofield; Nishiguchi [Journal of Organic Chemistry, 1988, vol. 53, # 21, p. 5097 - 5107]

12
[ 6317-89-1 ]
[ 116911-50-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: 42 percent / nitric acid / 3 h / -15 - -10 °C 2: 98 percent / K₂CO₃, methanol / 5 h / Ambient temperature 3: 98 percent / K₂CO₃, KI / dimethylformamide / 4 h / Ambient temperature 4: 83 percent / potassium tert-butoxide / dimethylformamide / 24 h / Ambient temperature 5: Zn, CaCl₂, C₂H₅OH, H₂O / 1.5 h / Heating 6: 1.) NaNO₂, SnCl₂*2H₂O, conc. HCl / 1.) 0 deg C, 2h, 2.) DMF, 0 deg C, 1h

Reference： [1]Sundberg; Baxter; Pitts; Ahmed-Schofield; Nishiguchi [Journal of Organic Chemistry, 1988, vol. 53, # 21, p. 5097 - 5107]

13
[ 6317-89-1 ]
[ 60207-18-3 ]

Reference： [1]Bulletin de la Societe Chimique de France,1952,p. 639
[2]Bulletin de la Societe Chimique de France,1952,p. 639
[3]Journal of Medicinal Chemistry,2013,vol. 56,p. 6033 - 6053

14
[ 6317-89-1 ]
[ 51410-08-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: AlCl₃
	Multi-step reaction with 2 steps 1: AlCl₃
	Multi-step reaction with 2 steps 1: aluminum (III) chloride / 5 h / 135 °C 2: potassium carbonate / acetone / 10 h / 55 °C

Reference： [1]Julia; Baillarge [Bulletin de la Societe Chimique de France, 1952, p. 639]
[2]Julia; Baillarge [Bulletin de la Societe Chimique de France, 1952, p. 639]
[3]Hu, Yun; Yang, Yaqi; Yu, Yanjun; Wen, Gesi; Shang, Nana; Zhuang, Wei; Lu, Dihan; Zhou, Binhua; Liang, Baoxia; Yue, Xin; Li, Feng; Du, Jun; Bu, Xianzhang [Journal of Medicinal Chemistry, 2013, vol. 56, # 15, p. 6033 - 6053]

15
[ 6317-89-1 ]
[ 2476-29-1 ]

Reference： [1]Bulletin de la Societe Chimique de France,1952,p. 639
[2]Journal of Medicinal Chemistry,2013,vol. 56,p. 6033 - 6053

16
[ 6317-89-1 ]
5-Amino-2-benzhydryl-phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 2: aqueous H₂SO₄

Reference： [1]Adams et al. [Journal of the American Chemical Society, 1955, vol. 77, p. 5617,5623]

17
[ 6317-89-1 ]
[ 16292-90-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: nitric acid 2: sulfuric acid

Reference： [1]Meldola; Stephens [Journal of the Chemical Society, 1906, vol. 89, p. 924]

18
[ 591-27-5 ]
[ 6317-89-1 ]

Yield	Reaction Conditions	Operation in experiment
	With acetic anhydride; zinc(II) oxide at 25℃; for 0.25h;	1 To a stirred mixture of 3-aminophenol (10 g, 91 mmol) and ZnO (8 g) was added acetic anhydride (10 mL, 92 mmol). The reaction mixture was stirred at room temperature for 15 min, dissolved in acetone (50 mL), the precipitate was filtered off, the filtrate was washed with acetone, and the solvent was evaporated in vacuo. The diacyl compound was dissolved in MeOH (130 mL) and after adding saturated solution of NaHCO3 the mixture was heated under reflux for 1 h. The solvent was evaporated in vacuo, the residue was acidified with HCl, and then extracted with EtOAc. The organic solution was dried and evaporation of solvent afforded crude monoacetylated compound (12.7 g) which was recrystallized from a mixture of CH2Cl2-MeOH (20:1). The precipitate was filtered and washed with CH2Cl2-MeOH until a white solid.Yield: 11.5 g (83.6%); Rt 0.6 (CH2Cl2-MeOH 9:1).
	With pyridine	13 2-amino-2-(6-heptyloxyquinolin-3-yl)-1-propanol Example 13 2-amino-2-(6-heptyloxyquinolin-3-yl)-1-propanol 3-aminophenol (19 g, 17 mol) was dissolved in Ac2O (162 g, 1.59 mol, 9.5 eq.), and pyridine (4.9 g, 0.062 mol, 0.36 eq.) was added. Then the reaction mixture was stirred at 80° C. over 2 h. Ice water (50 mL) was added to the mixture, and added saturated NaHCO3 solution to the mixture until pH=7, then extracted (ethyl acetate), washed (brine), dried (Na2SO4), concentrated to give 3-acetamidophenyl acetate as gray solid (30 g, yield: 93%). ESI-MS: 194 (M+H)+.
	With pyridine; sodium hydrogencarbonate	83 3-acetamidophenyl acetate Example 83 3-acetamidophenyl acetate 3-Aminophenol (19 g 0.17 mol) was dissolved in Ac2O (162 g, 1.59 mol, 9.5 eq.), and pyridine (4.9 g, 0.062 mol, 0.36 eq.) was added. Then the reaction mixture was stirred at 80° C. over 2 h. Ice water (50 mL) was added to the mixture, and saturated NaHCO3 solution was added to the mixture until pH=7, then extracted (EA), washed (brine), dried (Na2SO4), and concentrated to give 3-acetamidophenyl acetate as gray solid (30 g, yield: 93%). ESI-MS: 194 (M+H)+.

Reference： [1]Current Patent Assignee: Corporacion Quimico Farmaceutica Esteve SA - US2009/30013, 2009, A1 Location in patent: Page/Page column 10
[2]Current Patent Assignee: BIOGEN IDEC INC. - US2014/100195, 2014, A1 Location in patent: Page/Page column
[3]Current Patent Assignee: BIOGEN IDEC INC. - US2014/100195, 2014, A1 Location in patent: Page/Page column

19
[ 1189746-71-1 ]
[ 108-24-7 ]
[ 6317-89-1 ]

Yield	Reaction Conditions	Operation in experiment
49%	With methanesulfonic acid at 50℃; for 12h;

Reference： [1]Ishikawa, Teruhiko; Arai, Masaki; Nishiuchi, Hironori; Ishiguro, Hiroshi; Saito, Seiki [Chemistry Letters, 2008, vol. 37, # 10, p. 1066 - 1067]

20
[ 100-42-5 ]
[ 6317-89-1 ]
[ 1235283-83-6 ]

Yield	Reaction Conditions	Operation in experiment
47.1%	With silver hexafluoroantimonate; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; copper diacetate In tert-Amyl alcohol at 120℃; for 16h; Inert atmosphere; regioselective reaction;

Reference： [1]Patureau, Frederic W.; Glorius, Frank [Journal of the American Chemical Society, 2010, vol. 132, # 29, p. 9982 - 9983]

21
[ 6317-89-1 ]
[ 64-19-7 ]
[ 74332-02-8 ]

Yield	Reaction Conditions	Operation in experiment
57%	With boron trifluoride diethyl etherate; bis-[(trifluoroacetoxy)iodo]benzene at 20℃; for 0.5h; regioselective reaction;

Reference： [1]Location in patent: experimental part Liu, Huan; Wang, Xuemin; Gu, Yonghong [Organic and Biomolecular Chemistry, 2011, vol. 9, # 5, p. 1614 - 1620]

22
[ 6317-89-1 ]
[ 20628-19-7 ]