Name: 13041-60-6|Methyl 3-methoxy-2-naphthoate|96%
Brand: Ambeed
SKU: A201498
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1
[ 13041-60-6 ]
[ 883-62-5 ]

Yield	Reaction Conditions	Operation in experiment
96.4%	With sodium hydroxide In methanol; water at 40℃; for 2.5h;	10.2 (3) Preparation of 2-methoxy-3-naphthoic acid To a 250 mL single-neck flask equipped with a stir bar was added the product (11.2 g, 0.052 mol) obtained in the previous step, Anhydrous methanol 22. 4mL, 2N NaOH solution 67mL, Slowly heated to 40 ° C stirring reaction 2. 5h, TLC detection reaction is completed, Cooling, The reaction pH was adjusted to 2-3 with 2N HCl, Precipitation of a large number of yellow-white solid, Methanol filtration under vacuum, drying products 10. l g, the yield was 96.4%.
92%	With sodium hydroxide In methanol; water	2 Step 2. Step 2. 3-Methoxy-2-naphthoic acid A solution of methyl 3-methoxy-2-naphthoate (6.28 g, 29.10 mmol) and water (10 mL) in MeOH (100 mL) at room temp. was treated with a 1 N NaOH solution (33.4 mL, 33.4 mmol). The mixture was heated at the reflux temp. for 3 h, cooled to room temp., and made acidic with a 10% citric acid solution. The resulting solution was extracted with EtOAc (2*100 mL). The combined organic layers were washed with a saturated NaCl solution, dried (MgSO4) and concentrated under reduced pressure. The residue was triturated with hexane then washed several times with hexane to give 3-methoxy-2-naphthoic acid as a white solid (5.40 g, 92%): 1H-NMR (DMSO-d6) δ3.88 (s, 3H), 7.34-7.41 (m, 2H), 7.49-7.54 (m, 1H), 7.83 (d, J=8.09 Hz, 1H), 7.91 (d, J=8.09 Hz, 1H), 8.19 (s, 1H), 12.83 (br s, 1H).
92%	With sodium hydroxide In methanol; water	1.2 Step 2. Step 2. 3-Methoxy-2-naphthoic Acid A solution of methyl 3-methoxy-2-naphthoate (6.28 g, 29.10 mmol) and water (10 mL) in MeOH (100 mL) at room temp. was treated with a 1 N NaOH solution (33.4 mL, 33.4 mmol). The mixture was heated at the reflux temp. for 3 h, cooled to room temp., and made acidic with a 10% citric acid solution. The resulting solution was extracted with EtOAc (2*100 mL). The combined organic layers were washed with a saturated NaCl solution, dried (MgSO4) and concentrated under reduced pressure. The residue was triturated with hexane then washed several times with hexane to give 3-methoxy-2-naphthoic acid as a white solid (5.40 g, 92%): 1H-NMR (DMSO-d6) δ 3.88 (s, 3H), 7.34-7.41 (m, 2H), 7.49-7.54 (m, 1H), 7.83 (d, J=8.09 Hz, 1H), 7.91 (d, J=8.09 Hz, 1H), 8.19 (s, 1H), 12.83 (br s, 1H).

92%	With sodium hydroxide In methanol; water	2 Step 2. Step 2. 3-Methoxy-2-naphthoic acid A solution of methyl 3-methoxy-2-naphthoate (6.28 g, 29.10 mmol) and water (10 mL) in MeOH (100 mL) at room temp. was treated with a 1 N NaOH solution (33.4 mL, 33.4 mmol). The mixture was heated at the reflux temp. for 3 h, cooled to room temp., and made acidic with a 10% citric acid solution. The resulting solution was extracted with EtOAc (2*100 mL). The combined organic layers were washed with a saturated NaCl solution, dried (MgSO4) and concentrated under reduced pressure. The residue was triturated with hexane then washed several times with hexane to give 3-methoxy-2-naphthoic acid as a white solid (5.40 g, 92%): 1H-NMR (DMSO-d6) δ 3.88 (s, 3H), 7.34-7.41 (m, 2H), 7.49-7.54 (m, 1H), 7.83 (d, J=8.09 Hz, 1H), 7.91 (d, J=8.09 Hz, 1H), 8.19 (s, 1H), 12.83 (br s, 1H).
92%	With sodium hydroxide In methanol; water	2 Step 2. Step 2. 3-Methoxy-2-naphthoic acid A solution of methyl 3-methoxy-2-naphthoate (6.28 g, 29.10 mmol) and water (10 mL) in MeOH (100 mL) at room temp. was treated with a 1N NaOH solution (33.4 mL, 33.4 mmol). The mixture was heated at the reflux temp. for 3 h, cooled to room temp., and made acidic with a 10% citric acid solution. The resulting solution was extracted with EtOAc (2*100 mL). The combined organic layers were washed with a saturated NaCl solution, dried (MgSO4) and concentrated under reduced pressure. The residue was triturated with hexane then washed several times with hexane to give 3-methoxy-2-naphthoic acid as a white solid (5.40 g, 92%): 1H-NMR (DMSO-d6) δ3.88 (s, 3H), 7.34-7.41 (m, 2H), 7.49-7.54 (m, 1H), 7.83 (d, J=8.09 Hz, 1H), 7.91 (d, J=8.09 Hz, 1H), 8.19 (s, 1H), 12.83 (br s, 1H).
92%	With sodium hydroxide In methanol; water	A.2 3-Methoxy-2-naphthoic Acid Step 2 3-Methoxy-2-naphthoic Acid A solution of methyl 3-methoxy-2-naphthoate (6.28 g, 29.10 mmol) and water (10 mL) in MeOH (100 mL) at room temp was treated with a 1 N NaOH solution (33.4 mL, 33.4 mmol). The mixture was heated at the reflux temp for 3 h, cooling to room temp, and made acidic with a 10% citric acid solution. The resulting solution was extracted with EtOAc (2*100 mL). The combined organic layers were washed with a saturated NaCl solution, dried (MgSO4) and concentrated in vacuo. The residue was triturated with hexanes and washed several times with hexanes to give the desired carboxylic acid as a white crystalline solid (5.40 g, 92%): 1H-NMR (DMSO-d6) δ 3.88 (s, 3H), 7.34-7.41 (m, 2H), 7.49-7.54 (m, 1H), 7.83 (d, J=8.09 Hz, 1H), 7.91 (d, J=8.09 Hz, 1H), 8.19 (s, 1H), 12.83 (br s, 1H).
92%	Stage #1: methyl 3-methoxy-2-naphthoate With methanol; sodium hydroxide; water at 20℃; for 3h; Heating / reflux; Stage #2: With water; citric acid In methanol	A.6.2 Step 2. 3-Methoxy-2-naphthoic Acid A solution of methyl 3-methoxy-2-naphthoate (6.28 g, 29.10 mmol) and water (10 mL) in MeOH (100 ml) at room temp was treated with a 1 N NaOH solution (33.4 mL, 33.4 mmol). The mixture was heated at the reflux temp for 3 h, cooling to room temp, and made acidic with a 10% citric acid solution. The resulting solution was extracted with EtOAc (2*100 mL. The combined organic layers were washed with a saturated NaCl solution, dried (MgSO4) and concentrated in vacuo. The residue was triturated with hexanes and washed several times with hexanes to give the desired carboxylic acid as a white crystalline solid (5.40 g, 92%): 1H-NMR DMSO-d6) δ 3.88 (s, 3H), 7.34-7.41 (m, 21, 7.49-7.54 (m, 1H), 7.83 (d, J=8.09 Hz, 1H), 7.91 (d, J=8.09 Hz, 1H), 8.19 (s, 1H), 12.83 (br s, 1H).
92%	Stage #1: methyl 3-methoxy-2-naphthoate With methanol; sodium hydroxide; water at 20℃; for 3h; Heating / reflux; Stage #2: With citric acid at 20℃;	A.A1.2 Step 2. 3-Methoxy-2-naphthoic Acid A solution of methyl 3-methoxy-2-naphthoate (6.28 g, 29.10 mmol) and water (10 mL) in MeOH (100 mL) at room temp. was treated with a 1 N NaOH solution (33.4 mL, 33.4 mmol). The mixture was heated at the reflux temp. for 3 h, cooled to room temp., and made acidic with a 10% citric acid solution. The resulting solution was extracted with EtOAc (2*100 mL). The combined organic layers were washed with a saturated NaCl solution, dried (MgSO4) and concentrated under reduced pressure. The residue was triturated with hexane then washed several times with hexane to give 3-methoxy-2-naphthoic acid as a white solid (5.40 g, 92%): 1H-NMR (DMSO-d6) δ 3.88 (s, 3H), 7.34-7.41 (m, 2H), 7.49-7.54 (m, 1H), 7.83 (d, J=8.09 Hz, 1H), 7.91 (d, J=8.09 Hz, 1H), 8.19 (s, 1H), 12.83 (br s, 1H).
92%	With sodium hydroxide; water In methanol at 20℃; for 3h; Heating / reflux;	A.A6.2 A. General Methods for Synthesis of Substituted AnilinesA6. General Method for Aryl Amine Formation via Ether Formation Followed Ester Saponification, Curtius Rearrangement, and Carbamate DeprotectionStep 2. 3-Methoxy-2-naphthoic Acid A solution of methyl 3-methoxy-2-naphthoate (6.28 g, 29.10 mmol) and water (10 mL) in MeOH (100 mL) at room temp was treated with a 1 N NaOH solution (33.4 mL, 33.4 mmol). The mixture was heated at the reflux temp for 3 h, cooling to room temp, and made acidic with a 10% citric acid solution. The resulting solution was extracted with EtOAc (2 x 100 mL). The combined organic layers were washed with a saturated NaCl solution, dried (MgSO4) and concentrated in vacuo. The residue was triturated with hexanes and washed several times with hexanes to give the desired carboxylic acid as a white crystalline solid (5.40 g, 92%): 1H-NMR (DMSO-d6) ? 3.88 (s, 3H), 7.34-7.41 (m, 2H), 7.49-7.54 (m, 1H), 7.83 (d, J=8.09 Hz, 1H), 7.91 (d, J=8.09 Hz, 1H), 8.19 (s, 1H), 12.83 (br s, 1H).
92%	Stage #1: methyl 3-methoxy-2-naphthoate With methanol; sodium hydroxide; water at 20℃; for 3h; Heating / reflux; Stage #2: With citric acid In water	A6.2 Step 2. 3-Methoxy-2-naphthoic Acid; A solution of methyl 3-methoxy-2-naphthoate (6.28 g, 29.10 mmol) and water (10 mL) in MeOH (100 mL) at room temp was treated with a 1 N NaOH solution (33.4 mL, 33.4 mmol). The mixture was heated at the reflux temp for 3 h, cooling to room temp, and made acidic with a 10% citric acid solution. The resulting solution was extracted with EtOAc (2 x 100 mL). The combined organic layers were washed with a saturated NaCl solution, dried (MgSO4) and concentrated in vacuo. The residue was triturated with hexanes and washed several times with hexanes to give the desired carboxylic acid as a white crystalline solid (5.40 g, 92%): 1H-NMR (DMSO-d6) δ 3.88 (s, 3H), 7.34-7.41 (m, 2H), 7.49-7.54 (m, 1H), 7.83 (d, J=8.09 Hz, 1H), 7.91 (d,J=8.09 Hz, 1H), 8.19 (s, 1H), 12.83 (br s, 1H).
91%	With sodium hydroxide In water at 100℃; for 1.5h;
	With aqueous alkali
	With aqueous alcoholic alkali
	With potassium hydroxide In ethanol
	With potassium hydroxide In ethylene glycol at 130℃; for 6h; Inert atmosphere;

Reference： [1]Current Patent Assignee: SHENYANG PHARMACEUTICAL UNIVERSITY - CN105294637, 2016, A Location in patent: Paragraph 0152-0153
[2]Current Patent Assignee: BAYER AG - US2003/144278, 2003, A1
[3]Current Patent Assignee: BAYER AG - US2003/181442, 2003, A1
[4]Current Patent Assignee: BAYER AG - US2001/11135, 2001, A1
[5]Current Patent Assignee: BAYER AG - US2002/165394, 2002, A1
[6]Current Patent Assignee: BAYER AG - US2004/102636, 2004, A1
[7]Current Patent Assignee: Dumas, Jacques; Miller, Scott; Osterhout, Martin; Khire, Uday; Lowinger, Timothy B.; Riedl, Bernd; Scott, William J.; Smith, Roger A.; Wood, Jill E.; Gunn, David; Rodriguez, Martha; Wang, Ming; Turner, Tiffany; Brennan, Catherine - US2008/269265, 2008, A1 Location in patent: Page/Page column 10-11
[8]Current Patent Assignee: BAYER AG - US2003/207872, 2003, A1 Location in patent: Page/Page column 7
[9]Current Patent Assignee: BAYER AG - EP1449834, 2004, A2 Location in patent: Page 17
[10]Current Patent Assignee: BAYER AG - EP1042305, 2005, B1 Location in patent: Page/Page column 22
[11]Motomura, Takahisa; Nakamura, Hideko; Suginome, Michinori; Murakami, Masahiro; Ito, Yoshihiko [Bulletin of the Chemical Society of Japan, 2005, vol. 78, # 1, p. 142 - 146]
[12]Cohen; Dudley [Journal of the Chemical Society, 1910, vol. 97, p. 1747]
[13]Cohen; Dudley [Journal of the Chemical Society, 1910, vol. 97, p. 1747]
[14]Murphy; Kung; Kung; Billings [Journal of Medicinal Chemistry, 1990, vol. 33, # 1, p. 171 - 178]
[15]Zhao, Xiao-Jing; Li, Zi-Hao; Ding, Tong-Mei; Tian, Jin-Miao; Tu, Yong-Qiang; Wang, Ai-Fang; Xie, Yu-Yang [Angewandte Chemie - International Edition, 2021, vol. 60, # 13, p. 7061 - 7065][Angew. Chem., 2021, vol. 133, # 13, p. 7137 - 7141,5]

2
[ 13041-60-6 ]
[ 39110-92-4 ]

Yield	Reaction Conditions	Operation in experiment
99%	With lithium aluminium tetrahydride In diethyl ether for 12h; Heating;
93%	With lithium aluminium tetrahydride In tetrahydrofuran at 20℃; for 3h;
92%	With lithium aluminium tetrahydride In tetrahydrofuran at 20℃; for 2.25h; Inert atmosphere; Glovebox; Cooling with ice; Schlenk technique;

92%	With lithium aluminium tetrahydride In tetrahydrofuran at 20℃; for 2.25h; Schlenk technique; Inert atmosphere; Cooling with ice;	3 3-Methoxy-2-naphthalenemethanol (S9) Adapted from [5]. LAH (1.924 g, 50.68 mmol, 2.0 eq) was collected in a 250 mL schlenk flask from an argon filled glove box. Anhydrous THF (1 18 mL) was added to the LAH and stirred into a slurry, which was then lowered into an ice bath. In a separate 50 mL schlenk flask S8 was purged with N2 gas and anhydrous THF (29 mL) was added. The solution of S8 was added slowly over the course of 15 min to the mixing LAH slurry. Upon completion of the reaction, as monitored by TLC, of the addition the ice bath was removed and the reaction was allowed to mix at room temperature for 2 h. The reaction was then quenched with ice water and extracted 3 times with CH2CI2. The CH2CI2 was rinsed with brine, dried over Na2S04, and filtered. The CH2CI2 was removed in a rotary evaporator and the crude was purified using column chromatography (S1O2, 25% v/v EtOAc/hexanes) to yield a white solid. Yield 4.37 g (92%). Figure 41 shows 1 HNMR (400 MHz, CDCb, 25°C) d (ppm) 7.81 - 7.70 (m, 3H), 7.45 (d, J = 16.3 Hz, 1 H), 7.36 (d, J = 15.8 Hz, 1 H), 7.13 (s, 1 H), 4.83 (d, J = 6.5 Hz, 2H), 3.97 (s, 3H), 2.49 (d, J = 19.9 Hz, 1 H) spectra of compound S9. (0308) Figure 42 shows 13C NMR (101 MHz, CDC , 25°C) d (ppm) 156.03, 134.23, 130.61 , 128.79, 127.78, 127.64, 126.56, 126.44, 124.05, 105.28, 77.16, 62.55, 55.48 spectra of compound S9.
92%	With lithium aluminium tetrahydride In diethyl ether for 5h; Inert atmosphere; Reflux;	(7-Bromo-3-methoxynaphthalen-2-yl)methanol (5a). General procedure: In 2 L three-necked bottle, lithium aluminum hydride (16g, 0.42mol) was suspended in dry ether (200mL) under the nitrogen. To the stirred mixture was added dropwise a solution of Methyl 7-bromo-3-methoxy-2-naphthoate (4a, 116.2g, 0.39mol) dissolved in dry ether (1 L) keeping the solution boiling. Then the reaction was refluxed for about 5h and cooled to room temperature. Water (100mL) was added dropwise carefully. The inorganic material was filtered, and the ether was removed under reduced pressure. The residue was taken up in ethyl acetate, washed several times with water, dried over anhydrous magnesium sulfate, filtered and concentrated to get white crude product which was pure enough for next step (102.5g, 98%)
87%	With lithium aluminium tetrahydride In tetrahydrofuran at 20℃; for 6h;
85%	With lithium aluminium tetrahydride In tetrahydrofuran at 20℃; Inert atmosphere;
84%	With lithium borohydride In tetrahydrofuran; toluene at 100℃; for 2h; Inert atmosphere;
73%	Stage #1: methyl 3-methoxy-2-naphthoate With sodium bis(2-methoxyethoxy)aluminium dihydride In toluene at 0℃; for 2h; Stage #2: In toluene at 20℃; for 1h;	155.1 Example 155; 3-Benzhydryl-1-[(3-methoxy-2-naphtyl)methyl]-4-piperidinone A 50 ml round-bottomed flask was charged with 2.3 g (10.6 mmol) of 3-methoxy-2-naphthalenecarboxylic acid methyl ester and 18ml of toluene, and to the mixture was added 4.61 g (16 mmol) of NaAlH2(OCH2CH2OMe)2 with stirring under ice-cooling.. The mixture was further stirred for about 2 hours under ice-cooling and then for 1 hour at room temperature.. To the reaction mixture were added 20 ml of ethyl acetate and 20 ml of a 10% aqueous solution of Rochelle salt, the mixture was shaken and the organic layer was separated.. The aqueous layer was extracted once again with 20 ml of ethyl acetate, and the organic layers were combined and washed twice with 20 ml of water and then twice with 20 ml of a brine.. The organic layer was filtered through Celite, dried over MgSO4 (anhydrous), concentrated under reduced pressure to obtain 1.47 g of 3-methoxy-2-naphthylmethanol (yield: 73%).1H-NMR (CDCl3) δ: 3.96 (s, 3H), 4.82 (s, 2H), 7.12 (s, 1H), 7.19-7.51 (m, 2H), 7.72-7.80 (m, 3H).
68%	With lithium aluminium tetrahydride In tetrahydrofuran for 8h; Heating;
	With lithium aluminium tetrahydride; diethyl ether
	With lithium aluminium tetrahydride In diethyl ether at 0 - 20℃; for 4h; Inert atmosphere;
	With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; Inert atmosphere;

Reference： [1]Motomura, Takahisa; Nakamura, Hideko; Suginome, Michinori; Murakami, Masahiro; Ito, Yoshihiko [Bulletin of the Chemical Society of Japan, 2005, vol. 78, # 1, p. 142 - 146]
[2]Sawyer, J. Scott; Beight, Douglas W.; Smith, Edward C. R.; Snyder, David W.; Chastain, Marcia K.; Tielking, Richard L.; Hartley, Lawrence W.; Carlson, Donald G. [Journal of Medicinal Chemistry, 2005, vol. 48, # 3, p. 893 - 896]
[3]Newsome, Wesley J.; Ayad, Suliman; Cordova, Jesus; Reinheimer, Eric W.; Campiglia, Andres D.; Harper, James K.; Hanson, Kenneth; Uribe-Romo, Fernando J. [Journal of the American Chemical Society, 2019, vol. 141, # 28, p. 11298 - 11303]
[4]Current Patent Assignee: STATE UNIVERSITY SYSTEM OF FLORIDA - WO2019/126618, 2019, A1 Location in patent: Page/Page column 42; 44-45
[5]Cao, Ruiyuan; Fan, Shiyong; Li, Song; Liu, Ping; Lu, Yu; Wang, Bin; Wang, Xiaokui; Zhong, Wu [Bioorganic Chemistry, 2020, vol. 102]
[6]Wu, Kun-Chan; Lin, Yu-Shan; Yeh, Yu-Shan; Chen, Chun-Yen; Ahmed, Moawia O.; Chou, Pi-Tai; Hon, Yung-Son [Tetrahedron, 2004, vol. 60, # 51, p. 11861 - 11868]
[7]Legouin, Beatrice; Gayral, Maud; Uriac, Philippe; Cupif, Jean-Francois; Levoin, Nicolas; Toupet, Loic; Van De Weghe, Pierre [European Journal of Organic Chemistry, 2010, # 28, p. 5503 - 5508]
[8]Lucas, Simon; Heim, Ralf; Negri, Matthias; Antes, Iris; Ries, Christina; Schewe, Katarzyna E.; Bisi, Alessandra; Gobbi, Silvia; Hartmann, Rolf W. [Journal of Medicinal Chemistry, 2008, vol. 51, # 19, p. 6138 - 6149]
[9]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP1460062, 2004, A1 Location in patent: Page 65
[10]Yamamoto, Koji; Fukushima, Hitoshi; Yumioka, Hiroya; Nakazaki, Masao [Bulletin of the Chemical Society of Japan, 1985, vol. 58, # 12, p. 3633 - 3634]
[11]Ebnoether et al. [Helvetica Chimica Acta, 1952, vol. 35, p. 910,926]
[12]Alvarez-Bercedo, Paula; Martin, Ruben [Journal of the American Chemical Society, 2010, vol. 132, # 49, p. 17352 - 17353]
[13]Correa, Arkaitz; Leon, Thierry; Martin, Ruben [Journal of the American Chemical Society, 2014, vol. 136, # 3, p. 1062 - 1069]

3
[ 77-78-1 ]
[ 92-70-6 ]
[ 13041-60-6 ]

Yield	Reaction Conditions	Operation in experiment
97.5%	With potassium carbonate In acetone at 0 - 10℃; for 4h; Reflux; Inert atmosphere;	10.1 (1) Preparation of methyl 2-methoxy-3-naphthoate 10.0 g (0.055 mol) of 2-hydroxy-3-naphthoic acid was weighed out, was added to 250 mL of a three-neck flask equipped with a stir bar, Add 100mL acetone stirring until the raw materials dissolved, Slowly add anhydrous K2C03 18. 4g (0. 133m0l) control the internal temperature of 0 ° C, 11.6 mL (0.122 mol) of dimethyl sulfate was slowly added dropwise, The argon was added during the dropwise addition, So that the internal temperature is less than 10 ° C. Drop Bi, After slowly heating to reflux for 4 h, the reaction was complete by TLC, dropping to room temperature, and adding 10 mL of water to destroy unreacted dimethyl sulfate. Reaction solution appears a lot of viscous solid, stirring lh after suction filtration, The filter cake was washed with a small amount of acetone, The filtrate was concentrated, The resulting residue was extracted with CH2Cl2 and H20, Dried and concentrated to give the product 11. 2g, yield 97. 5%.
88%	With potassium carbonate In acetone for 12h; Reflux;
81%	With potassium carbonate In acetone for 10h; Reflux;	Methyl 7-bromo-3-methoxy-2-naphthoate (4a). General procedure: In 2 L three-necked bottle, 7-bromo-3-hydroxy-2- naphthoic acid (3, 112g, 0.42mol) was suspended in acetone (1 L). To this mechanically stirred mixture was added anhydrous potassium carbonate (288g, 2.08mol) and dimethyl sulfate (99mL, 1.05mol). The reaction was refluxed for about 10h, then cooled to room temperature and water (50mL) was added stirred for 2h to destroy any remaining dimethyl sulfate. The inorganic material was filtered and the acetone was removed under reduced pressure. The residue was taken up in methylene chloride, washed several times with water, dried over anhydrous magnesium sulfate, filtered, concentrated and recrystallized in ethyl acetate and petroleum ether to afford white product (105.6g, 86%).

	With potassium hydroxide
	With potassium carbonate

Reference： [1]Current Patent Assignee: SHENYANG PHARMACEUTICAL UNIVERSITY - CN105294637, 2016, A Location in patent: Paragraph 0150-0151
[2]Legouin, Beatrice; Gayral, Maud; Uriac, Philippe; Cupif, Jean-Francois; Levoin, Nicolas; Toupet, Loic; Van De Weghe, Pierre [European Journal of Organic Chemistry, 2010, # 28, p. 5503 - 5508]
[3]Cao, Ruiyuan; Fan, Shiyong; Li, Song; Liu, Ping; Lu, Yu; Wang, Bin; Wang, Xiaokui; Zhong, Wu [Bioorganic Chemistry, 2020, vol. 102]
[4]Werner; Seybold [Chemische Berichte, 1904, vol. 37, p. 3659]
[5]Alvarez-Bercedo, Paula; Martin, Ruben [Journal of the American Chemical Society, 2010, vol. 132, # 49, p. 17352 - 17353]

4
[ 13041-60-6 ]
[ 75-05-8 ]
3-(3-methoxynaphthalen-2-yl)-3-oxopropanenitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With sodium hydride In tetrahydrofuran; mineral oil for 2h; Inert atmosphere; Reflux;
	With sodium methylate

Reference： [1]Havel, Stepan; Khirsariya, Prashant; Akavaram, Naresh; Paruch, Kamil; Carbain, Benoit [Journal of Organic Chemistry, 2018, vol. 83, # 24, p. 15380 - 15405]
[2]Long [Journal of the American Chemical Society, 1947, vol. 69, p. 990,993]

5
[ 883-99-8 ]
[ 74-88-4 ]
[ 13041-60-6 ]

Yield	Reaction Conditions	Operation in experiment
91%	With caesium carbonate for 32h; Heating;
89%	With 18-crown-6 ether; potassium carbonate In acetone for 12h; Heating;
84%	Stage #1: 3-hydroxy-2-naphthoic acid methyl ester With 18-crown-6 ether; potassium carbonate In acetone at 20℃; for 2h; Stage #2: methyl iodide In acetone for 32h; Reflux;

70.4%	Stage #1: 3-hydroxy-2-naphthoic acid methyl ester With potassium carbonate In acetone for 0.25h; Stage #2: methyl iodide In acetone Reflux;	1.b b) methyl 3-methoxy-2-naphthoate (1b) The obtained intermediate 1a (10.1 g, 0.05 mol) was dissolved in 150 ml of acetone, and excess potassium carbonate was added thereto, and the reaction was stirred for 15 minutes. The methylating reagent methyl iodide was added dropwise and refluxed overnight. The next day, TLC monitored the reaction completely (petroleum ether/ethyl acetate = 4/1) and was taken to room temperature. The reaction was concentrated to dryness. After adding water, ethyl acetate was extracted, and the combined organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to dryness. Filtration gave a white solid 7.6 g, yield: 70.4 %.
	With sodium methylate
	With potassium carbonate In water; N,N-dimethyl-formamide	1.1 Step 1. Step 1. Methyl 3-methoxy-2-naphthoate A slurry of methyl 3-hydroxy-2-naphthoate (10.1 g, 50.1 mmol) and K2CO3 (7.96 g, 57.6 mmol) in DMF (200 mL) was stirred at room temp. for 15 min., then treated with iodomethane (3.43 mL, 55.1 mmol). The mixture was allowed to stir at room temp. overnight, then was treated with water (200 mL). The resulting mixture was extracted with EtOAc (2*200 mL). The combined organic layers were washed with a saturated NaCl solution (100 mL), dried (MgSO4), concentrated under reduced pressure (approximately 0.4 mmHg overnight) to give methyl 3-methoxy-2-naphthoate as an amber oil (10.30 g): 1H-N (DMSO-d,) δ 2.70 (s, 3H), 2.85 (s, 3H), 7.38 (app t, J=8.09 Hz, 1H), 7.44 (s, 1H), 7.53 (app t, J=8.09 Hz, 1H), 7.84 (d, J=8.09 Hz, 1H), 7.90 (s, 1H), 8.21 (s, 1H).
	With potassium carbonate In water; N,N-dimethyl-formamide	1 Step 1. Step 1. Methyl 3-methoxy-2-naphthoate A slurry of methyl 3-hydroxy-2-naphthoate (10.1 g, 50.1 mmol) and K2CO3 (7.96 g, 57.6 mmol) in DMF (200 mL) was stirred at room temp. for 15 min., then treated with iodomethane (3.43 mL, 55.1 mmol). The mixture was allowed to stir at room temp. overnight, then was treated with water (200 mL). The resulting mixture was extracted with EtOAc (2*200 mL). The combined organic layers were washed with a saturated NaCl solution (100 mL), dried (MgSO4), concentrated under reduced pressure (approximately 0.4 mmHg overnight) to give methyl 3-methoxy-2-naphthoate as an amber oil (10.30 g): 1H-NMR (DMSO-d6) δ 2.70 (s, 3H), 2.85 (s, 3H), 7.38 (app t, J=8.09 Hz, 1H), 7.44 (s, 1H), 7.53 (app t, J=8.09 Hz, 1H), 7.84 (d, J=8.09 Hz, 1H), 7.90 (s, 1H), 8.21 (s, 1H).
	With potassium carbonate In water; N,N-dimethyl-formamide	1 Step 1. Step 1. Methyl 3-methoxy-2-naphthoate A slurry of methyl 3-hydroxy-2-naphthoate (10.1 g, 50.1 mmol) and K2CO3 (7.96 g, 57.6 mmol) in DMF (200 mL) was stirred at room temp. for 15 min., then treated with iodomethane (3.43 mL, 55.1 mmol). The mixture was allowed to stir at room temp. overnight, then was treated with water (200 mL). The resulting mixture was extracted with EtOAc (2*200 mL). The combined organic layers were washed with a saturated NaCl solution (100 mL), dried (MgSO4), concentrated under reduced pressure (approximately 0.4 mmHg overnight) to give methyl 3-methoxy-2-naphthoate as an amber oil (10.30 g): 1H-NMR (DMSO-d6) δ2.70 (s, 3H), 2.85 (s, 3H), 7.38 (app t, J=8.09 Hz, 1H), 7.44 (s, 1H), 7.53 (app t, J=8.09 Hz, 1H), 7.84 (d, J=8.09 Hz, 1H), 7.90 (s, 1H), 8.21 (s, 1H).
	With potassium carbonate In water; N,N-dimethyl-formamide	A.1 Methyl 3-Methoxy-2-naphthoate Step 1 Methyl 3-Methoxy-2-naphthoate A slurry of methyl 3-hydroxy-2-naphthoate (10.1 g, 50.1 mmol) and K2CO3 (7.96 g, 57.6 mmol) in DMF (200 mL) was stirred at room temp for 15 min, then treated with iodomethane (3.43 mL, 55.1 mmol). The mixture was allowed to stir at room temp overnight, then was treated with water (200 mL). The resulting mixture was extracted with EtOAc (2*200 mL). The combined organic layers were washed with a saturated NaCl solution (100 mL), dried (MgSO4), concentrated in vacuo (approximately 0.4 mmHg overnight) to give the desired ether as an amber oil (10.30 g): 1H-NMR (DMSO-d6) δ 2.70 (s, 3H), 2.85 (s, 3H), 7.38 (app t, J=8.09 Hz, 1H), 7.44 (s, 1H), 7.53 (app t, J=8.09 Hz, 1H), 7.84 (d, J=8.09 Hz, 1H), 7.90 (s, 1H), 8.21 (s, 1H).
	Stage #1: 3-hydroxy-2-naphthoic acid methyl ester With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 0.25h; Stage #2: methyl iodide In N,N-dimethyl-formamide at 20℃;	A6.1 A6. General Method for Aryl Amine Formation Via Ether Formation Followed Ester Saponification, Curtius Rearrangement, and Carbamate Deprotection; Step 1. Methyl 3-Methoxy-2-naphthoate; A slurry of methyl 3-hydroxy-2-naphthoate (10.1 g, 50.1 mmol) and K2CO3 (7.96 g, 57.6 mmol) in DMF (200 mL) was stirred at room temp for 15 min, then treated with iodomethane (3.43 mL, 55.1 mmol). The mixture was allowed to stir at room temp overnight, then was treated with water (200 mL). The resulting mixture was extracted with EtOAc (2×200 mL). The combined organic layers were washed with a saturated NaCl solution (100 mL), dried (MgSO4), concentrated in vacuo (approximately 0.4 mmHg overnight) to give the desired ether as an amber oil (10.30 g): 1H-NMR (DMSO-d6) δ 2.70 (s, 3H), 2.85 (s, 3H), 7.38 (app t, J=8.09 Hz, 1H), 7.44 (s, 1H), 7.53 (app t, J=8.09 Hz, 1H), 7.84 (d, J=8.09 Hz, 1H), 7.90 (s, 1H), 8.21 (s, 1H).
	Stage #1: 3-hydroxy-2-naphthoic acid methyl ester With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 0.25h; Stage #2: methyl iodide In N,N-dimethyl-formamide at 20℃;	A.A1.1 Step 1. Methyl 3-methoxy-2-naphthoate A slurry of methyl 3-hydroxy-2-naphthoate (10.1 g, 50.1 mmol) and K2CO3 (7.96 g, 57.6 mmol) in DMF (200 mL) was stirred at room temp. for 15 min., then treated with iodomethane (3.43 mL, 55.1 mmol). The mixture was allowed to stir at room temp. overnight, then was treated with water (200 mL). The resulting mixture was extracted with EtOAc (2*200 mL). The combined organic layers were washed with a saturated NaCl solution (100 mL), dried (MgSO4), concentrated under reduced pressure (approximately 0.4 mmHg overnight) to give methyl 3-methoxy-2-naphthoate as an amber oil (10.30 g): 1H-NMR (DMSO-d6) δ 2.70 (s, 3H), 2.85 (s, 3H), 7.38 (app t, J=8.09 Hz, 1H), 7.44 (s, 1H), 7.53 (app t, J=8.09 Hz, 1H), 7.84 (d, J=8.09 Hz, 1H), 7.90 (s, 1H), 8.21 (s, 1H).
	Stage #1: 3-hydroxy-2-naphthoic acid methyl ester With potassium carbonate In DMF (N,N-dimethyl-formamide) at 20℃; for 0.25h; Stage #2: methyl iodide In DMF (N,N-dimethyl-formamide) at 20℃;	A6.1 A6. General Method for Aryl Amine Formation via Ether Formation Followed Ester Saponification, Curtius Rearrangement, and Carbamate Deprotection; [] Step 1. Methyl 3-Methoxy-2-naphthoate: A slurry of methyl 3-hydroxy-2-naphthoate (10.1 g, 50.1 mmol) and K2CO3 (7.96 g, 57.6 mmol) in DMF (200 mL) was stirred at room temp for 15 min, then treated with iodomethane (3.43 mL, 55.1 mmol). The mixture was allowed to stir at room temp overnight, then was treated with water (200 mL). The resulting mixture was extracted with EtOAc (2 x 200 mL). The combined organic layers were washed with a saturated NaCl solution (100 mL), dried (MgSO4), concentrated in vacuo (approximately 0.4 mmHg overnight) to give the desired ether as an amber oil (10.30 g): 1H-NMR (DMSO-d6) δ 2.70 (s, 3H), 2.85 (s, 3H), 7.38 (app t, J=8.09 Hz, 1H), 7.44 (s, 1H), 7.53 (app t, J=8.09 Hz, 1H), 7.84 (d, J=8.09 Hz, 1H), 7.90 (s, 1H), 8.21 (s, 1H).

Reference： [1]Sawyer, J. Scott; Beight, Douglas W.; Smith, Edward C. R.; Snyder, David W.; Chastain, Marcia K.; Tielking, Richard L.; Hartley, Lawrence W.; Carlson, Donald G. [Journal of Medicinal Chemistry, 2005, vol. 48, # 3, p. 893 - 896]
[2]Wu, Kun-Chan; Lin, Yu-Shan; Yeh, Yu-Shan; Chen, Chun-Yen; Ahmed, Moawia O.; Chou, Pi-Tai; Hon, Yung-Son [Tetrahedron, 2004, vol. 60, # 51, p. 11861 - 11868]
[3]Lucas, Simon; Heim, Ralf; Negri, Matthias; Antes, Iris; Ries, Christina; Schewe, Katarzyna E.; Bisi, Alessandra; Gobbi, Silvia; Hartmann, Rolf W. [Journal of Medicinal Chemistry, 2008, vol. 51, # 19, p. 6138 - 6149]
[4]Current Patent Assignee: ZHEJIANG UNIVERSITY - CN108329232, 2018, A Location in patent: Paragraph 0087; 0088
[5]Cohen; Dudley [Journal of the Chemical Society, 1910, vol. 97, p. 1747]
[6]Current Patent Assignee: BAYER AG - US2003/181442, 2003, A1
[7]Current Patent Assignee: BAYER AG - US2001/11135, 2001, A1
[8]Current Patent Assignee: BAYER AG - US2002/165394, 2002, A1 Current Patent Assignee: BAYER AG - US2003/144278, 2003, A1
[9]Current Patent Assignee: BAYER AG - US2004/102636, 2004, A1
[10]Current Patent Assignee: Dumas, Jacques; Miller, Scott; Osterhout, Martin; Khire, Uday; Lowinger, Timothy B.; Riedl, Bernd; Scott, William J.; Smith, Roger A.; Wood, Jill E.; Gunn, David; Rodriguez, Martha; Wang, Ming; Turner, Tiffany; Brennan, Catherine - US2008/269265, 2008, A1 Location in patent: Page/Page column 10
[11]Current Patent Assignee: BAYER AG - US2003/207872, 2003, A1 Location in patent: Page/Page column 6-7
[12]Current Patent Assignee: BAYER AG - EP1042305, 2005, B1 Location in patent: Page/Page column 21

6
[ 82261-01-6 ]
[ 92-70-6 ]
[ 13041-60-6 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate In acetone

Reference： [1]Murphy; Kung; Kung; Billings [Journal of Medicinal Chemistry, 1990, vol. 33, # 1, p. 171 - 178]

7
[ 13041-60-6 ]
[ 565-80-0 ]
[ 232938-30-6 ]

Yield	Reaction Conditions	Operation in experiment
52.1%	With lithium aluminium tetrahydride; titanium(III) chloride; triethylamine In tetrahydrofuran for 2h; Heating;

Reference： [1]Watanabe, Nobuko; Kobayashi, Hisako; Azami, Mitsunori; Matsumoto, Masakatsu [Tetrahedron, 1999, vol. 55, # 22, p. 6831 - 6840]

8
[ 92-70-6 ]
[ 74-88-4 ]
[ 13041-60-6 ]

Yield	Reaction Conditions	Operation in experiment
96%	With potassium carbonate In N,N-dimethyl-formamide at 80℃; Inert atmosphere;
96%	With potassium carbonate In N,N-dimethyl-formamide at 80℃; Inert atmosphere;	3 Methyl 3-methoxy-2-naphthanoate (S8) Adapted from [4] 3-hydroxy-2- naphthanoic acid (5.0 g, 26.6 mmol, 1.0 eq) and K2CO3 (14.7 g, 106.3 mmol, 4.0 eq) were added to a 250 ml_ round bottom flask. The flask was evacuated to 150 mtorr and back filled with nitrogen gas three times. Anhydrous DMF (60 ml_) was then added and stirred in the round bottom flask. Mel (8.60 ml_, 138.2 mmol, 5.2 eq) was added to the flask and the mixture was heated to 80 °C for 24 h. After which the vessel was cooled to room temperature and the excess carbonate was quenched by the addition of 3 M H2SO4. The solution was then diluted to 500 mL using Dl water. The solution was extracted with EtOAc (x3). The combined organic extracts were rinsed with 75 mL of 2 M LiCI (x1 ), 175 mL water (x3), and brine (x1 ) after which the EtOAc was dried over Na2S04 and filtered. The ethyl acetate was removed using a rotary evaporator and the crude product was subjected to column chromatography, (S1O2, 7% v/v (0302) EtOAc/hexanes). Yield 5.48 g (96%). (0303) Figure 39 shows 1HNMR (400 MHz, CDCI3, 25°C) d (ppm) 8.30 (s, 1 H), 7.81 (d, J = 8.9 Hz, 1 H), 7.73 (d, J = 9.0 Hz, 1 H), 7.51 (t, J = 8.2 Hz, 1 H), 7.37 (t, J = 8.1 Hz, (0304) 1 H), 7.20 (s, 1 H), 3.98 (d, J = 15.4 Hz, 6H) spectra of compound S8. (0305) Figure 40 shows 13C NMR (101 MHz, CDCI3, 25°C) d (ppm) 166.80, 155.81 , 136.20, 132.89, 128.79, 128.52, 127.62, 126.55, 124.50, 121.80, 106.88, 77.16, 56.09, 52.38 spectra of compound S8.
92%	With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 96h;

Stage #1: 3-Hydroxy-2-naphthoic acid With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.5h; Inert atmosphere; Stage #2: methyl iodide In N,N-dimethyl-formamide at 0 - 20℃; for 10h; Inert atmosphere;

Reference： [1]Newsome, Wesley J.; Ayad, Suliman; Cordova, Jesus; Reinheimer, Eric W.; Campiglia, Andres D.; Harper, James K.; Hanson, Kenneth; Uribe-Romo, Fernando J. [Journal of the American Chemical Society, 2019, vol. 141, # 28, p. 11298 - 11303]
[2]Current Patent Assignee: STATE UNIVERSITY SYSTEM OF FLORIDA - WO2019/126618, 2019, A1 Location in patent: Page/Page column 42-44
[3]Motomura, Takahisa; Nakamura, Hideko; Suginome, Michinori; Murakami, Masahiro; Ito, Yoshihiko [Bulletin of the Chemical Society of Japan, 2005, vol. 78, # 1, p. 142 - 146]
[4]Zhao, Xiao-Jing; Li, Zi-Hao; Ding, Tong-Mei; Tian, Jin-Miao; Tu, Yong-Qiang; Wang, Ai-Fang; Xie, Yu-Yang [Angewandte Chemie - International Edition, 2021, vol. 60, # 13, p. 7061 - 7065][Angew. Chem., 2021, vol. 133, # 13, p. 7137 - 7141,5]

9
[ 13041-60-6 ]
[ 161564-43-8 ]
3-(3-methoxy-naphthalene-2-carbonyl)-2-oxo-piperidine-1-carbaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With sodium methylate In methanol; toluene for 10h; Heating;

Reference： [1]Nenajdenko; Gololobov; Zakurdaev; Balenkova [Russian Chemical Bulletin, 2003, vol. 52, # 11, p. 2473 - 2482]

10
[ 13041-60-6 ]
3,3’-dimethoxy-2,2’-binaphthalene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 91 percent / NaOH / H₂O / 1.5 h / 100 °C 2: SOCl₂ / 1 h / 20 °C 3: 2.30 g / 2,2'-azobis(isobutyronitrile); CBrCl₃; 2-mercaptopyridine N-oxide sodium salt / 0.75 h / Heating 4: 94 percent / ZnBr₂ / PdCl₂(dppp) / tetrahydrofuran / 80 °C

Reference： [1]Motomura, Takahisa; Nakamura, Hideko; Suginome, Michinori; Murakami, Masahiro; Ito, Yoshihiko [Bulletin of the Chemical Society of Japan, 2005, vol. 78, # 1, p. 142 - 146]

11
[ 13041-60-6 ]
[ 68251-77-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 91 percent / NaOH / H₂O / 1.5 h / 100 °C 2: SOCl₂ / 1 h / 20 °C 3: 2.30 g / 2,2'-azobis(isobutyronitrile); CBrCl₃; 2-mercaptopyridine N-oxide sodium salt / 0.75 h / Heating

Reference： [1]Motomura, Takahisa; Nakamura, Hideko; Suginome, Michinori; Murakami, Masahiro; Ito, Yoshihiko [Bulletin of the Chemical Society of Japan, 2005, vol. 78, # 1, p. 142 - 146]

12
[ 13041-60-6 ]
[ 61873-80-1 ]

Yield	Reaction Conditions	Operation in experiment
63%	With bis(1,5-cyclooctadiene)nickel ⁽⁰⁾; 1,1,3,3-Tetramethyldisiloxane; potassium <i>tert</i>-butylate; 1,3-bis(cyclohexyl)imidazolium tetrafluoroborate In toluene at 110℃; for 12h; Glovebox; Inert atmosphere; Sealed tube;
	Multi-step reaction with 2 steps 1: 99 percent / LiAlH₄ / diethyl ether / 12 h / Heating 2: 97 percent / hydrogen / Pd/C / ethyl acetate / 7.5 h
	Multi-step reaction with 3 steps 1: LiAlH₄; diethyl ether 3: LiAlH₄; THF

Reference： [1]Cook, Adam; Prakash, Sekar; Zheng, Yan-Long; Newman, Stephen G. [Journal of the American Chemical Society, 2020, vol. 142, # 18, p. 8109 - 8115]
[2]Motomura, Takahisa; Nakamura, Hideko; Suginome, Michinori; Murakami, Masahiro; Ito, Yoshihiko [Bulletin of the Chemical Society of Japan, 2005, vol. 78, # 1, p. 142 - 146]
[3]Ebnoether et al. [Helvetica Chimica Acta, 1952, vol. 35, p. 910,926]

13
[ 13041-60-6 ]
[ 17324-04-8 ]

Reference： [1]Bulletin of the Chemical Society of Japan,2005,vol. 78,p. 142 - 146
[2]Helvetica Chimica Acta,1952,vol. 35,p. 910,926

14
[ 13041-60-6 ]
[ 58778-69-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 91 percent / NaOH / H₂O / 1.5 h / 100 °C 2: SOCl₂ / 1 h / 20 °C
	Multi-step reaction with 2 steps 1: KOH / ethanol 2: SOCl₂, N,N-dimethylformamide / CHCl₃ / 3 h / Heating
	Multi-step reaction with 2 steps 1: sodium hydroxide / methanol; water / 2.5 h / 40 °C 2: thionyl chloride / 5 h / 80 °C / Inert atmosphere

Reference： [1]Motomura, Takahisa; Nakamura, Hideko; Suginome, Michinori; Murakami, Masahiro; Ito, Yoshihiko [Bulletin of the Chemical Society of Japan, 2005, vol. 78, # 1, p. 142 - 146]
[2]Murphy; Kung; Kung; Billings [Journal of Medicinal Chemistry, 1990, vol. 33, # 1, p. 171 - 178]
[3]Current Patent Assignee: SHENYANG PHARMACEUTICAL UNIVERSITY - CN105294637, 2016, A

15
[ 13041-60-6 ]
[ 939-15-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 99 percent / LiAlH₄ / diethyl ether / 12 h / Heating 2: 97 percent / hydrogen / Pd/C / ethyl acetate / 7.5 h 3: HBr; acetic acid / H₂O / 6.5 h / 130 °C 4: 40 percent / PPh₃; bromine / 1.5 h / 310 °C

Reference： [1]Motomura, Takahisa; Nakamura, Hideko; Suginome, Michinori; Murakami, Masahiro; Ito, Yoshihiko [Bulletin of the Chemical Society of Japan, 2005, vol. 78, # 1, p. 142 - 146]

16
[ 13041-60-6 ]
[ 56679-88-0 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 893 - 896
[2]Tetrahedron,2004,vol. 60,p. 11861 - 11868
[3]Journal of the American Chemical Society,2019,vol. 141,p. 11298 - 11303
[4]Patent: WO2019/126618,2019,A1

17
[ 13041-60-6 ]
[ 443911-34-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 93 percent / LiAlH₄ / tetrahydrofuran / 3 h / 20 °C 2: 92 percent / 4-methylmorpholine N-oxide; tetrapropylammonium perruthenate / CH₂Cl₂ 3: 75 percent / NaOEt / diethyl ether / 22 h / 10 - 20 °C 4: 82 percent / toluene / 3 h / Heating

Reference： [1]Sawyer, J. Scott; Beight, Douglas W.; Smith, Edward C. R.; Snyder, David W.; Chastain, Marcia K.; Tielking, Richard L.; Hartley, Lawrence W.; Carlson, Donald G. [Journal of Medicinal Chemistry, 2005, vol. 48, # 3, p. 893 - 896]

18
[ 13041-60-6 ]
[ 443911-33-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 93 percent / LiAlH₄ / tetrahydrofuran / 3 h / 20 °C 2: 92 percent / 4-methylmorpholine N-oxide; tetrapropylammonium perruthenate / CH₂Cl₂ 3: 75 percent / NaOEt / diethyl ether / 22 h / 10 - 20 °C

Reference： [1]Sawyer, J. Scott; Beight, Douglas W.; Smith, Edward C. R.; Snyder, David W.; Chastain, Marcia K.; Tielking, Richard L.; Hartley, Lawrence W.; Carlson, Donald G. [Journal of Medicinal Chemistry, 2005, vol. 48, # 3, p. 893 - 896]

19
[ 13041-60-6 ]
[ 443911-45-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: 93 percent / LiAlH₄ / tetrahydrofuran / 3 h / 20 °C 2.1: 92 percent / 4-methylmorpholine N-oxide; tetrapropylammonium perruthenate / CH₂Cl₂ 3.1: 75 percent / NaOEt / diethyl ether / 22 h / 10 - 20 °C 4.1: 82 percent / toluene / 3 h / Heating 5.1: NaH / dimethylformamide / 0.5 h 5.2: 90 percent / dimethylformamide / 168 h / 20 °C 6.1: 94 percent / LiAlH₄ / tetrahydrofuran / 2 h / 20 °C 7.1: 82 percent / PdCl₂; NaBH₄ / methanol; tetrahydrofuran / 1 h / 20 °C

Reference： [1]Sawyer, J. Scott; Beight, Douglas W.; Smith, Edward C. R.; Snyder, David W.; Chastain, Marcia K.; Tielking, Richard L.; Hartley, Lawrence W.; Carlson, Donald G. [Journal of Medicinal Chemistry, 2005, vol. 48, # 3, p. 893 - 896]

20
[ 13041-60-6 ]
1-cyclohexylmethyl-2-methyl-1H-benzo[g]indol-4-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1.1: 93 percent / LiAlH₄ / tetrahydrofuran / 3 h / 20 °C 2.1: 92 percent / 4-methylmorpholine N-oxide; tetrapropylammonium perruthenate / CH₂Cl₂ 3.1: 75 percent / NaOEt / diethyl ether / 22 h / 10 - 20 °C 4.1: 82 percent / toluene / 3 h / Heating 5.1: NaH / dimethylformamide / 0.5 h 5.2: 90 percent / dimethylformamide / 168 h / 20 °C 6.1: 94 percent / LiAlH₄ / tetrahydrofuran / 2 h / 20 °C 7.1: 82 percent / PdCl₂; NaBH₄ / methanol; tetrahydrofuran / 1 h / 20 °C 8.1: BBr₃ / CH₂Cl₂ / 1 h / 20 °C

Reference： [1]Sawyer, J. Scott; Beight, Douglas W.; Smith, Edward C. R.; Snyder, David W.; Chastain, Marcia K.; Tielking, Richard L.; Hartley, Lawrence W.; Carlson, Donald G. [Journal of Medicinal Chemistry, 2005, vol. 48, # 3, p. 893 - 896]

21
[ 13041-60-6 ]
[ 443911-44-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: 93 percent / LiAlH₄ / tetrahydrofuran / 3 h / 20 °C 2.1: 92 percent / 4-methylmorpholine N-oxide; tetrapropylammonium perruthenate / CH₂Cl₂ 3.1: 75 percent / NaOEt / diethyl ether / 22 h / 10 - 20 °C 4.1: 82 percent / toluene / 3 h / Heating 5.1: NaH / dimethylformamide / 0.5 h 5.2: 90 percent / dimethylformamide / 168 h / 20 °C 6.1: 94 percent / LiAlH₄ / tetrahydrofuran / 2 h / 20 °C

Reference： [1]Sawyer, J. Scott; Beight, Douglas W.; Smith, Edward C. R.; Snyder, David W.; Chastain, Marcia K.; Tielking, Richard L.; Hartley, Lawrence W.; Carlson, Donald G. [Journal of Medicinal Chemistry, 2005, vol. 48, # 3, p. 893 - 896]

22
[ 13041-60-6 ]
[ 443911-46-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1.1: 93 percent / LiAlH₄ / tetrahydrofuran / 3 h / 20 °C 2.1: 92 percent / 4-methylmorpholine N-oxide; tetrapropylammonium perruthenate / CH₂Cl₂ 3.1: 75 percent / NaOEt / diethyl ether / 22 h / 10 - 20 °C 4.1: 82 percent / toluene / 3 h / Heating 5.1: NaH / dimethylformamide / 0.5 h 5.2: 90 percent / dimethylformamide / 168 h / 20 °C 6.1: 94 percent / LiAlH₄ / tetrahydrofuran / 2 h / 20 °C 7.1: 82 percent / PdCl₂; NaBH₄ / methanol; tetrahydrofuran / 1 h / 20 °C 8.1: BBr₃ / CH₂Cl₂ / 1 h / 20 °C 9.1: 0.23 g / Cs₂CO₃ / dimethylformamide / 29 h / 20 °C

Reference： [1]Sawyer, J. Scott; Beight, Douglas W.; Smith, Edward C. R.; Snyder, David W.; Chastain, Marcia K.; Tielking, Richard L.; Hartley, Lawrence W.; Carlson, Donald G. [Journal of Medicinal Chemistry, 2005, vol. 48, # 3, p. 893 - 896]

23
[ 13041-60-6 ]
[ 443911-43-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: 93 percent / LiAlH₄ / tetrahydrofuran / 3 h / 20 °C 2.1: 92 percent / 4-methylmorpholine N-oxide; tetrapropylammonium perruthenate / CH₂Cl₂ 3.1: 75 percent / NaOEt / diethyl ether / 22 h / 10 - 20 °C 4.1: 82 percent / toluene / 3 h / Heating 5.1: NaH / dimethylformamide / 0.5 h 5.2: 90 percent / dimethylformamide / 168 h / 20 °C

Reference： [1]Sawyer, J. Scott; Beight, Douglas W.; Smith, Edward C. R.; Snyder, David W.; Chastain, Marcia K.; Tielking, Richard L.; Hartley, Lawrence W.; Carlson, Donald G. [Journal of Medicinal Chemistry, 2005, vol. 48, # 3, p. 893 - 896]

24
[ 13041-60-6 ]
(3-chlorooxalyl-1-cyclohexylmethyl-2-methyl-1H-benzo[g]indol-4-yloxy)-acetic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 10 steps 1.1: 93 percent / LiAlH₄ / tetrahydrofuran / 3 h / 20 °C 2.1: 92 percent / 4-methylmorpholine N-oxide; tetrapropylammonium perruthenate / CH₂Cl₂ 3.1: 75 percent / NaOEt / diethyl ether / 22 h / 10 - 20 °C 4.1: 82 percent / toluene / 3 h / Heating 5.1: NaH / dimethylformamide / 0.5 h 5.2: 90 percent / dimethylformamide / 168 h / 20 °C 6.1: 94 percent / LiAlH₄ / tetrahydrofuran / 2 h / 20 °C 7.1: 82 percent / PdCl₂; NaBH₄ / methanol; tetrahydrofuran / 1 h / 20 °C 8.1: BBr₃ / CH₂Cl₂ / 1 h / 20 °C 9.1: 0.23 g / Cs₂CO₃ / dimethylformamide / 29 h / 20 °C 10.1: CH₂Cl₂ / 1 h / 0 °C

Reference： [1]Sawyer, J. Scott; Beight, Douglas W.; Smith, Edward C. R.; Snyder, David W.; Chastain, Marcia K.; Tielking, Richard L.; Hartley, Lawrence W.; Carlson, Donald G. [Journal of Medicinal Chemistry, 2005, vol. 48, # 3, p. 893 - 896]

25
[ 13041-60-6 ]
(3-aminooxalyl-1-cyclohexylmethyl-2-methyl-1H-benzo[g]indol-4-yloxy)-acetic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 12 steps 1.1: 93 percent / LiAlH₄ / tetrahydrofuran / 3 h / 20 °C 2.1: 92 percent / 4-methylmorpholine N-oxide; tetrapropylammonium perruthenate / CH₂Cl₂ 3.1: 75 percent / NaOEt / diethyl ether / 22 h / 10 - 20 °C 4.1: 82 percent / toluene / 3 h / Heating 5.1: NaH / dimethylformamide / 0.5 h 5.2: 90 percent / dimethylformamide / 168 h / 20 °C 6.1: 94 percent / LiAlH₄ / tetrahydrofuran / 2 h / 20 °C 7.1: 82 percent / PdCl₂; NaBH₄ / methanol; tetrahydrofuran / 1 h / 20 °C 8.1: BBr₃ / CH₂Cl₂ / 1 h / 20 °C 9.1: 0.23 g / Cs₂CO₃ / dimethylformamide / 29 h / 20 °C 10.1: CH₂Cl₂ / 1 h / 0 °C 11.1: 94 mg / NH₃ / CH₂Cl₂; dioxane / 0.33 h 12.1: 54 percent / aq. LiOH / tetrahydrofuran; methanol / 28 h / 20 °C

Reference： [1]Sawyer, J. Scott; Beight, Douglas W.; Smith, Edward C. R.; Snyder, David W.; Chastain, Marcia K.; Tielking, Richard L.; Hartley, Lawrence W.; Carlson, Donald G. [Journal of Medicinal Chemistry, 2005, vol. 48, # 3, p. 893 - 896]

26
[ 13041-60-6 ]
[ 443911-29-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 11 steps 1.1: 93 percent / LiAlH₄ / tetrahydrofuran / 3 h / 20 °C 2.1: 92 percent / 4-methylmorpholine N-oxide; tetrapropylammonium perruthenate / CH₂Cl₂ 3.1: 75 percent / NaOEt / diethyl ether / 22 h / 10 - 20 °C 4.1: 82 percent / toluene / 3 h / Heating 5.1: NaH / dimethylformamide / 0.5 h 5.2: 90 percent / dimethylformamide / 168 h / 20 °C 6.1: 94 percent / LiAlH₄ / tetrahydrofuran / 2 h / 20 °C 7.1: 82 percent / PdCl₂; NaBH₄ / methanol; tetrahydrofuran / 1 h / 20 °C 8.1: BBr₃ / CH₂Cl₂ / 1 h / 20 °C 9.1: 0.23 g / Cs₂CO₃ / dimethylformamide / 29 h / 20 °C 10.1: CH₂Cl₂ / 1 h / 0 °C 11.1: 94 mg / NH₃ / CH₂Cl₂; dioxane / 0.33 h

Reference： [1]Sawyer, J. Scott; Beight, Douglas W.; Smith, Edward C. R.; Snyder, David W.; Chastain, Marcia K.; Tielking, Richard L.; Hartley, Lawrence W.; Carlson, Donald G. [Journal of Medicinal Chemistry, 2005, vol. 48, # 3, p. 893 - 896]

27
[ 13041-60-6 ]
[ 581-71-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 87 percent / LiAlH₄ / tetrahydrofuran / 6 h / 20 °C 2: 82 percent / pyridinium chlorochromate; sodium acetate; molecular sieves 4 Angstroem / CH₂Cl₂ / 0.67 h 3: 80 percent / BBr₃ / CH₂Cl₂ / 1 h / 20 °C
	Multi-step reaction with 3 steps 1: lithium aluminium tetrahydride / tetrahydrofuran / 2.25 h / 20 °C / Inert atmosphere; Glovebox; Cooling with ice; Schlenk technique 2: pyridinium chlorochromate; potassium acetate / dichloromethane / 2.08 h / 0 - 20 °C / Schlenk technique; Inert atmosphere; Molecular sieve 3: boron tribromide / dichloromethane / 0 - 20 °C / Inert atmosphere; Schlenk technique
	Multi-step reaction with 3 steps 1: lithium aluminium tetrahydride / tetrahydrofuran / 2.25 h / 20 °C / Schlenk technique; Inert atmosphere; Cooling with ice 2: potassium acetate; pyridinium chlorochromate / dichloromethane / 2.08 h / 0 - 20 °C / Schlenk technique; Inert atmosphere; Molecular sieve 3: boron tribromide / dichloromethane / 1.08 h / 0 - 20 °C / Inert atmosphere; Schlenk technique

Reference： [1]Wu, Kun-Chan; Lin, Yu-Shan; Yeh, Yu-Shan; Chen, Chun-Yen; Ahmed, Moawia O.; Chou, Pi-Tai; Hon, Yung-Son [Tetrahedron, 2004, vol. 60, # 51, p. 11861 - 11868]
[2]Newsome, Wesley J.; Ayad, Suliman; Cordova, Jesus; Reinheimer, Eric W.; Campiglia, Andres D.; Harper, James K.; Hanson, Kenneth; Uribe-Romo, Fernando J. [Journal of the American Chemical Society, 2019, vol. 141, # 28, p. 11298 - 11303]
[3]Current Patent Assignee: STATE UNIVERSITY SYSTEM OF FLORIDA - WO2019/126618, 2019, A1

28
[ 13041-60-6 ]
3-hydroxy-4-(1,4,7,10-tetraoxa-13-azacyclopentadec-13-ylmethyl)naphthalene-2-carbaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: 87 percent / LiAlH₄ / tetrahydrofuran / 6 h / 20 °C 2.1: 82 percent / pyridinium chlorochromate; sodium acetate; molecular sieves 4 Angstroem / CH₂Cl₂ / 0.67 h 3.1: 80 percent / BBr₃ / CH₂Cl₂ / 1 h / 20 °C 4.1: 4 h / 20 °C 4.2: 71 percent / CH₂Cl₂ / 6 h / 20 °C

Reference： [1]Wu, Kun-Chan; Lin, Yu-Shan; Yeh, Yu-Shan; Chen, Chun-Yen; Ahmed, Moawia O.; Chou, Pi-Tai; Hon, Yung-Son [Tetrahedron, 2004, vol. 60, # 51, p. 11861 - 11868]

29
[ 13041-60-6 ]
[ 187961-95-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 52.1 percent / LiAlH₄; titanium(III) trichloride; triethylamine / tetrahydrofuran / 2 h / Heating 2: 50.4 percent / ethanethiol; NaH / dimethylformamide / 2 h / Heating 3: 72.2 percent / imidazole / dimethylformamide / 20 °C

Reference： [1]Watanabe, Nobuko; Kobayashi, Hisako; Azami, Mitsunori; Matsumoto, Masakatsu [Tetrahedron, 1999, vol. 55, # 22, p. 6831 - 6840]

30
[ 13041-60-6 ]
[ 232938-36-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 52.1 percent / LiAlH₄; titanium(III) trichloride; triethylamine / tetrahydrofuran / 2 h / Heating 2: 50.4 percent / ethanethiol; NaH / dimethylformamide / 2 h / Heating

Reference： [1]Watanabe, Nobuko; Kobayashi, Hisako; Azami, Mitsunori; Matsumoto, Masakatsu [Tetrahedron, 1999, vol. 55, # 22, p. 6831 - 6840]

31
[ 13041-60-6 ]
[ 187961-96-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 52.1 percent / LiAlH₄; titanium(III) trichloride; triethylamine / tetrahydrofuran / 2 h / Heating 2: 50.4 percent / ethanethiol; NaH / dimethylformamide / 2 h / Heating 3: 72.2 percent / imidazole / dimethylformamide / 20 °C 4: 58.1 percent / tetraphenylporphin; O₂ / CH₂Cl₂ / -78 - 0 °C / Photolysis

Reference： [1]Watanabe, Nobuko; Kobayashi, Hisako; Azami, Mitsunori; Matsumoto, Masakatsu [Tetrahedron, 1999, vol. 55, # 22, p. 6831 - 6840]

32
[ 13041-60-6 ]
[ 105259-35-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 13 steps 1: 68 percent / LiAlH₄ / tetrahydrofuran / 8 h / Heating 2: 81 percent / PBr₃ / diethyl ether / 4 h / Ambient temperature 3: 1) C₂H₅ONa 4: 7 g / KOH / ethanol; H₂O / 3 h / Heating 5: 1 h / 200 °C 6: 6.7 g / conc. aq. H₂SO₄ 7: 93 percent / LiAlH₄ / tetrahydrofuran / Heating 8: 61 percent / PBr₃ / diethyl ether / Ambient temperature 9: 95 percent / ethanol; H₂O / 6 h / Heating 10: 95 percent / KOH / ethanol; H₂O / 4 h / Heating 11: 89 percent / polyphosphoric acid / 1 h / 60 °C 12: 75 percent / N₂H₄*H₂O, KOH / bis-(2-hydroxy-ethyl) ether / Heating 13: 93 percent / conc. aq. HCl / acetic acid; H₂O / 15 h / Heating