Name: 1700-30-7|(3-(Benzyloxy)phenyl)methanol|98%
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SKU: A325444
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1
[ 1700-37-4 ]
[ 1700-30-7 ]

Yield	Reaction Conditions	Operation in experiment
99%	With sodium tetrahydridoborate In methanol at 0 - 20℃; for 2h; Inert atmosphere;
98%	With sodium tetrahydridoborate In tetrahydrofuran at 23℃; for 4h;
87%	With sodium tetrahydridoborate In methanol at 0℃; for 0.5h;

	With lithium aluminium hydride; diethyl ether
	With sodium tetrahydridoborate
	With sodium tetrahydridoborate In ethanol; dichloromethane
	With sodium tetrahydridoborate In methanol; dichloromethane for 1h;
	With sodium tetrahydridoborate In isopropanol
	With sodium tetrahydridoborate In methanol at 20℃;
	With sodium tetrahydridoborate In methanol
	With lithium aluminium hydride In tetrahydrofuran at 20℃; for 2h; Inert atmosphere;	4.1.2.1. 3-Benzyloxybenzyl bromide (3c) 3-Hydroxybenzaldehyde (5.00 g, 0.041 mol) was dissolved in anhydrous acetonitrile (130 mL) under argon atmosphere. Cesium carbonate (20.01 g, 0.061 mol) was added and the suspension stirred for 5 min. Benzyl bromide (11.69 mL, 0.102 mol) was then added and the solution heated at reflux for 16 h. The solution was concentrated on rotary evaporator, water was added and the mixture was extracted with EtOAc. The organic phase was washed twice with water, once with brine, dried over MgSO4, filtered and concentrated. Water was added and the mixture was extracted with CH2Cl2. The crude product was purified by flash chromatography on silica gel with hexanes/EtOAc (80/20) to yield 3a as a white solid (8.59 g). 1H NMR δ (CDCl3) 5.13 (s, 2H, PhCH2O), 5.33 (s, 2H, COOCH2Ph), 7.35-7.50 (m, 9H, 2-CH, 4-CH, 5-CH, 6-CH and PhCH2O), 10.00 (s, 1H, PhCHO). The aldehyde 3a was dissolved in anhydrous THF (200 mL) under argon and cooled to 0 °C. Lithium aluminum hydride (1.55 g, 0.041 mol) was added in small portions and the solution stirred at room temperature for 2 h. The reaction was then quenched using water (0.8 mL), a 10% wt aqueous NaOH solution (1.15 mL) and water again (1.9 mL) and left to settle. The suspension was then filtered and concentrated. Water was added and the mixture extracted with EtOAc, the organic phase dried over MgSO4, filtered and concentrated to yield 7.07 g crude alcohol 3b. 1H NMR δ (CDCl3) 4.68 (s, 2H, PhCH2OH), 5.08 (s, 2H, PhCH2O), 6.90-7.46 (m, 9H, 2-CH, 4-CH, 5-CH, 6-CH and PhCH2O).
	With sodium tetrahydridoborate In methanol at 0℃; Inert atmosphere;
	With sodium tetrahydridoborate; ethanol; calcium(II) chloride In tetrahydrofuran at 0 - 20℃;	The intermediate 33 (8.2 mmols) and calcium chloride (16.4 mmols) were dissolved in 55 mL of anhydrous ethanol and 27 mLs of THF. The solution was next cooled to 0° C. and sodium borohydride (16.4 mmols) was added slowly over several minutes to the reaction vessel. Upon warming to ambient temperature, the mixture was allowed to stir for an additional 15 hours. After this time, the flask was again cooled to 0° C. and the excess sodium borohydride was quenched with the addition of 5 mLs of 1N HCl. The aqueous layer was extracted with four 20 mL portions of EtOAc; the organic layers were then combined, washed with 10 mLs of brine and dried with MgSO4. After evaporation, the crude organic material was purified by flash chromatography and 6.7 mmols of the title product was recovered. 1H NMR (300 MHz, CDCl3) δ 7.49-7.24 (m, 5H), 7.06-6.88 (m, 2H), 5.08 (s, 21-1), 4.66 (s, 2H), 1.78 (s, 1H). 13C NMR (75 MHz, CDCl3) δ 129.88, 128.83, 128.21, 127.72, 119.60, 114.35, 113.45, 70.17, 65.46.
	With lithium tetrahydridoborate; ethanol In tetrahydrofuran Cooling with ice;
	With methanol; sodium tetrahydridoborate for 1h; Cooling with ice;	5.1.3. Phenylmethanol (8a) General procedure: To a solution of compound 7a (1.06 g, 10 mmol) in methanol(10 mL) was added NaBH4 (0.57 g, 15 mmol). After stirring for 1 hwhile cooled with an ice-water bath, methanol was evaporatedand the residue was dissolved in EtOAc (100 mL). The organic layerwas washed with water (3 100 mL) and brine (3 100 mL), anddried over MgSO4 overnight. EtOAc was evaporated to give 8a ascolorless oil (2.01 g, yield: 94%). ESI-MS m/z 109.4 [M+H]+. The crude product was used directly in the next reaction without furtherpurification. Compounds 8b-8u, 8aa-8ff, 10v-10w, 17a-17b and 22a-22hwere prepared using the same procedure described above
	With sodium tetrahydridoborate In methanol at 0 - 20℃; for 2h;

Reference： [1]Nagasawa, Shota; Fujiki, Shogo; Sasano, Yusuke; Iwabuchi, Yoshiharu [Journal of Organic Chemistry, 2021, vol. 86, # 9, p. 6952 - 6968]
[2]Thakkar, Kshitij; Geahlen, Robert L.; Cushman, Mark [Journal of Medicinal Chemistry, 1993, vol. 36, # 20, p. 2950 - 2955]
[3]Sayama, Misa; Inoue, Asuka; Nakamura, Sho; Jung, Sejin; Ikubo, Masaya; Otani, Yuko; Uwamizu, Akiharu; Kishi, Takayuki; Makide, Kumiko; Aoki, Junken; Hirokawa, Takatsugu; Ohwada, Tomohiko [Journal of Medicinal Chemistry, 2017, vol. 60, # 14, p. 6384 - 6399]
[4]Oki; Iwamura [Bulletin of the Chemical Society of Japan, 1959, vol. 32, p. 955,958]
[5]Baxter,I. et al. [Journal of the Chemical Society, 1965, p. 3645 - 3660]
[6]Robin, Jean-Pierre; Landais, Yannick [Tetrahedron, 1992, vol. 48, # 5, p. 819 - 830]
[7]Van Oeveren; Jansen; Feringa [Journal of Organic Chemistry, 1994, vol. 59, # 20, p. 5999 - 6007]
[8]Yang, Li-Ming; Lin, Shwu-Jiuan; Yang, Tsang-Hsiung; Lee, Kuo-Hsiung [Bioorganic and Medicinal Chemistry Letters, 1996, vol. 6, # 8, p. 941 - 944]
[9]Lisowski, Vincent; Enguehard, Cecile; Lancelot, Jean-Charles; Caignard, Daniel-Henri; Lambel, Stephanie; Leonce, Stephane; Pierre, Alain; Atassi, Ghanem; Renard, Pierre; Rault, Sylvain [Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 16, p. 2205 - 2208]
[10]Renaudet, Olivier; Reymond, Jean-Louis [Organic Letters, 2004, vol. 6, # 3, p. 397 - 400]
[11]Location in patent: experimental part Fournier, Diane; Poirier, Donald [European Journal of Medicinal Chemistry, 2011, vol. 46, # 9, p. 4227 - 4237]
[12]Fan, Yi Chiao; Kwon, Ohyun [Organic Letters, 2012, vol. 14, # 13, p. 3264 - 3267]
[13]Current Patent Assignee: UNIVERSITY OF VIRGINIA - US2012/214858, 2012, A1 Location in patent: Page/Page column 29
[14]Klöck, Cornelius; Herrera, Zachary; Albertelli, Megan; Khosla, Chaitan [Journal of Medicinal Chemistry, 2014, vol. 57, # 21, p. 9042 - 9064]
[15]Cao, Jiangying; Ma, Chunhua; Zang, Jie; Gao, Shuai; Gao, Qianwen; Kong, Xiujie; Yan, Yugang; Liang, Xuewu; Ding, Qin'ge; Zhao, Chunlong; Wang, Binghe; Xu, Wenfang; Zhang, Yingjie [Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 12, p. 3145 - 3157]
[16]Wang, Hui; Yang, Ren-Yin; Xu, Bo [Chemistry - A European Journal, 2022, vol. 28, # 23]

3
[ 1700-30-7 ]
[ 24033-03-2 ]

Yield	Reaction Conditions	Operation in experiment
94%	With thionyl chloride In dichloromethane at 0℃; for 3h;
80%	With thionyl chloride In benzene for 2.5h; Heating;
67%	With methanesulfonyl chloride; triethylamine In dichloromethane at 0℃;	2 To a solution of 3-benzyloxybenzyl alcohol (3.0g, 14.0mmol) in dichloromethane (30mL) was added methanesulfonyl chloride (1.39mL, 16.8mmol) and triethylamine (2.34mL, 16.8mmol) on an ice bath, and the solution was stirred overnight. The reaction solution was diluted with dichloromethane, washed with aqueous solution of 5% sodium bicarbonate, and then, dried over anhydrous magnesium sulfate. The solvent was evaporated, then, the residue was purified by silica gel column chromatography (hexane : ethyl acetate = 10 : 1), and 1-benzyloxy-3-chloromethyl-benzene (2.2g, 67%) was obtained as a colorless oil. Next, to a solution of iminodicarboxylic acid di-tert-butyl ester (2.12g, 8.76mmol) in N,N-dimethylformamide (13mL) was added sodium hydride (0.39g, 9.86mmol, 60% in oil), the solution was stirred at 60°C for 6 hours, 1-benzyloxy-3-chloromethyl-benzene (1.0g, 4.30mmol) was added, and the solution was further stirred at 60°C for 4 hours. The reaction solution was allowed to room temperature, then, dichloromethane and water were added for partitioning, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated, then, the residue was purified by silica gel column chromatography (hexane : ethyl acetate =10:1), and (3-benzyloxybenzyl) iminodicarboxylic acid di-tert-butyl ester (691 mg, 39%) was obtained as a pale yellow oil. Lastly, (3-benzyloxybenzyl) iminodicarboxylic acid di-tert butyl ester (691 mg, 1.67mmol) was cooled on an ice bath, trifluoroacetic acid (3mL) was added, and the solution was stirred for 30 minutes. An aqueous solution of saturated sodium bicarbonate was added to the reaction solution, which was then extracted with ethyl acetate and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the title compound (292mg, 82%) was obtained as a white waxy solid. This was used in the next reaction without further purification.

	With pyridine; thionyl chloride
	With thionyl chloride
	With thionyl chloride In dichloromethane for 0.5h;
	With thionyl chloride In 1,4-dioxane at 20℃;
	With thionyl chloride In dichloromethane; N,N-dimethyl-formamide at 40℃; for 4h;
8.66 g	With thionyl chloride In dichloromethane at 0℃; for 3h;	3.3. 1-(Benzyloxy)-3-(chloromethyl)benzene (18) To a solution of above product 17 (9.37 g, 43.8 mmol) in DCM (150 mL) at 0 was added thionyl chloride (4.8 mL, 65.7 mmol) and stirred at the same temperature for 3 h. the reaction mixture was concentrated in vacuo and the residue was purified by chromatography (petroleum ether/ethyl acetate, 10/1) to afford 18 (8.66 g, 85% for two steps) as colorless oil.
	With thionyl chloride In dichloromethane; N,N-dimethyl-formamide at 20 - 40℃; for 4h;	4.1.2. General synthetic procedure for target compounds 1-4 General procedure: To a solution of the obtained benzyl alcohol 2a (1 equiv) in dichloromethane(20 ml) was slowly added thionyl chloride (6 equiv) anda catalytic amount of DMF at room temperature. After stirring at 40 °Cfor 4 h, the reaction was concentrated under reduced pressure. Theresidue was purified by silica gel column chromatography using amixture of petroleum ether/ethyl acetate (20:1, v/v) as eluent to affordthe desired product 3a. To a solution of the obtained chlorinated intermediates3a (1 equiv) and 4a (1.1 equiv) in acetone was addedK2CO3 (2 equiv) and a catalytic amount of KI at room temperature. Thereaction mixture was heated to 60 °C with stirring overnight. Then thereaction mixture was cooled to room temperature followed by filtrationand the filtrate was concentrated under vacuum. The residue waspurified by silica gel column chromatography using a mixture of petroleumether/ethyl acetate (5:1, v/v) as eluent to afford a white solid.To a solution of the obtained solid (1 equiv) in 2:3:1 THF/MeOH/H2O(18 ml) was added LiOH·H2O (1.5 equiv). After stirring at room temperaturefor 4 h, the volatiles were removed under reduced pressure.The residue was acidified with 1 N hydrochloric acid solution, and thenfiltered and the filter cake was washed with 5 ml of water, dried invacuum to afford a white powder. Recrystallization from EtOH gave thetarget compounds as colorless crystals.

Reference： [1]Lee, Jeewoo; Lee, Ju-Hyun; Kim, Su Yeon; Perry, Nicholas A.; Lewin, Nancy E.; Ayres, Jolene A.; Blumberg, Peter M. [Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 6, p. 2022 - 2031]
[2]Ono; Katsube [Chemical and Pharmaceutical Bulletin, 1983, vol. 31, # 4, p. 1267 - 1276]
[3]Current Patent Assignee: EISAI CO LTD - EP1669348, 2006, A1 Location in patent: Page/Page column 77
[4]France,D.J. et al. [Tetrahedron, 1969, vol. 25, p. 4011 - 4022]
[5]Kametani,T. et al. [Journal of the Chemical Society. Perkin transactions I, 1973, p. 471 - 472] Pinder; Burger; Ariens [Arzneimittel-Forschung/Drug Research, 1970, vol. 20, # 2, p. 245 - 246]
[6]Kelley, James L.; Krochmal, Mark P.; Linn, James A.; McLean, Ed W.; Soroko, Francis E. [Journal of Medicinal Chemistry, 1988, vol. 31, # 3, p. 606 - 612]
[7]Lisowski, Vincent; Enguehard, Cecile; Lancelot, Jean-Charles; Caignard, Daniel-Henri; Lambel, Stephanie; Leonce, Stephane; Pierre, Alain; Atassi, Ghanem; Renard, Pierre; Rault, Sylvain [Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 16, p. 2205 - 2208]
[8]Li, Zheng; Yang, Jianyong; Gu, Weijie; Cao, Guoshen; Fu, Xiaoting; Sun, Xuedan; Zhang, Yu; Jin, Hui; Huang, Wenlong; Qian, Hai [RSC Advances, 2016, vol. 6, # 52, p. 46356 - 46365]
[9]Bi, Fangchao; Ji, Shengli; Venter, Henrietta; Liu, Jingru; Semple, Susan J.; Ma, Shutao [Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 5, p. 884 - 891]
[10]Li, Zheng; Chen, Yueming; Zhang, Yuhan; Jiang, Hongwei; Liu, Yanzhi; Chen, Yufang; Zhang, Luyong; Qian, Hai [Bioorganic Chemistry, 2018, vol. 80, p. 296 - 302]

4
[ 1700-30-7 ]
[ 1700-31-8 ]

Yield	Reaction Conditions	Operation in experiment
97%	With phosphorus tribromide; In diethyl ether;	Synthesis of Compound 172 Preparation of (3-benzyloxy)benzyl bromide: To a solution of (3-benzyloxy)benzyl alcohol (3.0 g, 14.0 mmol) in anhydrous diethyl ether (50 mL) was added PBr3 (0.66 mL, 7.0 mmol) in one portion, and the resulting mixture was stirred at room temperature for 3 hours. The mixture was diluted with diethyl ether (60 mL) and washed with H2O (240 mL), saturated NaHCO3 (240 mL), and brine (2*40 mL). The ether layer was dried over anhydrous MgSO4, and the solvent was removed under reduced pressure to afford (3-benzyloxy)benzyl bromide (3.76 g, 97percent) as a pale yellow solid.
97%	With phosphorus tribromide; In diethyl ether;	Synthesis of Compound 172 Preparation of (3-benzyloxy)benzyl bromide: To a solution of (3-benzyloxy)benzyl alcohol (3.0 g, 14.0 mmol) in anhydrous diethyl ether (50 mL) was added PBr3 (0.66 mL, 7.0 mmol) in one portion, and the resulting mixture was stirred at room temperature for 3 hours. The mixture was diluted with diethyl ether (60 mL) and washed with H2O (240 mL), saturated NaHCO3 (240 mL), and brine (2*40 mL). The ether layer was dried over anhydrous MgSO4, and the solvent was removed under reduced pressure to afford (3-benzyloxy)benzyl bromide (3.76 g, 97percent) as a pale yellow solid.
89%	With phosphorus tribromide; In dichloromethane; at 0 - 20℃; for 3h;	Using the procedure reported by K. Thakkar et al., J. Med. Chem., 1993, 36 (20), 2950. [0500] Phosphorus tribromide (1.96 mL, 20.6 mmol) was added to a solution of 3-benzyloxybenzyl alcohol (4.29 g, 20 mmol) in anhydrous dichloromethane (90 mL) at 0° C. The mixture was stirred at 0° C. for 2 h and then at room temperature for 1 h. The reaction was poured onto ice/water (400 mL) and allowed to warm to room temperature. The aqueous solution was extracted with Et2O (5.x.100 mL) and the combined ethereal solution dried (MgSO4). Concentration in vacuo gave a light yellow oil which crystallised on standing to give OBS01018 as colourless needles (4.93 g, 89percent). TLC [SiO2, EtOAc-n-hexane (1:1)] Rf=0.9; m.p. 55-56° C. [Lit. (Petroleum ether): 55° C.]; 1H-NMR (400 MHz, CDCl3) 4.44 (2H, s), 5.05 (2H, s); 6.78 (1H, d, J=2), 6.93 (1H, m), 7.22 (1H, t, J=8), 7.40 (5H, m).

64%	With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 20℃; for 2h;	3-Hydroxybenzaldehyde (5.00 g, 0.041 mol) was dissolved in anhydrous acetonitrile (130 mL) under argon atmosphere. Cesium carbonate (20.01 g, 0.061 mol) was added and the suspension stirred for 5 min. Benzyl bromide (11.69 mL, 0.102 mol) was then added and the solution heated at reflux for 16 h. The solution was concentrated on rotary evaporator, water was added and the mixture was extracted with EtOAc. The organic phase was washed twice with water, once with brine, dried over MgSO4, filtered and concentrated. Water was added and the mixture was extracted with CH2Cl2. The crude product was purified by flash chromatography on silica gel with hexanes/EtOAc (80/20) to yield 3a as a white solid (8.59 g). 1H NMR delta (CDCl3) 5.13 (s, 2H, PhCH2O), 5.33 (s, 2H, COOCH2Ph), 7.35-7.50 (m, 9H, 2-CH, 4-CH, 5-CH, 6-CH and PhCH2O), 10.00 (s, 1H, PhCHO). The aldehyde 3a was dissolved in anhydrous THF (200 mL) under argon and cooled to 0 °C. Lithium aluminum hydride (1.55 g, 0.041 mol) was added in small portions and the solution stirred at room temperature for 2 h. The reaction was then quenched using water (0.8 mL), a 10percent wt aqueous NaOH solution (1.15 mL) and water again (1.9 mL) and left to settle. The suspension was then filtered and concentrated. Water was added and the mixture extracted with EtOAc, the organic phase dried over MgSO4, filtered and concentrated to yield 7.07 g crude alcohol 3b. 1H NMR delta (CDCl3) 4.68 (s, 2H, PhCH2OH), 5.08 (s, 2H, PhCH2O), 6.90-7.46 (m, 9H, 2-CH, 4-CH, 5-CH, 6-CH and PhCH2O). Crude alcohol 3b (7.06 g) was dissolved in anhydrous CH2Cl2 (330 mL) and the solution cooled to 0 °C. Triphenylphosphine (17.28 g, 0.066 mol) and carbon tetrabromide (21.85 g, 0.066 mol) were then added and the solution stirred at room temperature for 2 h. The reaction mixture was quenched with water and extracted with CH2Cl2. The organic phase was dried over MgSO4, filtered and concentrated. The product was purified by flash chromatography on silica gel with hexanes/EtOAc (9/1) to yield 5.85 g (64percent) of bromide 3c. 1H NMR delta (CDCl3) 4.47 (s, 2H, PhCH2Br), 5.07 (s, 2H, PhCH2O), 6.90-7.46 (m, 9H, 2-CH, 4-CH, 5-CH, 6-CH and PhCH2O); 13C NMR (75 MHz) delta (acetone-d6) 32.5, 69.4, 114.3, 114.8, 121.0, 127.0 (2.x.), 127.2, 127.8, 128.0, 129.3, 136.1, 138.6, 158.3.
56%	With phosphorus tribromide; In diethyl ether; at 20℃; for 3h;Cooling with ice;	In an ice cooled solution of 3-benzyloxy-phenylmethanol (2.14 g, 10 mmol) in Et2O (25 mL), PBr333 (1.41 mL, 15 mmol) was added dropwise. The mixture was stirred at room temperature for 3 h and the reaction mixture was quenched by the addition of H2O (15 mL) in small portions at 0 °C. The aqueous phase was removed and the organic layer was washed with H2O, dried over Na2SO4 and evaporated in vacuo. The product was purified by column chromatography (silica gel) using petroleum ether (bp 40-60 °C)-EtOAc, 7:3 as eluent. Yield 1.5 g (56percent); yellow oil.1H NMR (CDCl3) delta: 7.42-6.82(m, 9H, Ph), 5.06(s, 2H, OCH2Ph), 4.46(s, 2H, BrCH2Ph).13C NMR delta: 159.0, 139.2, 136.7, 129.8, 128.6, 128.0, 127.5, 121.5, 115.4, 114.9 70.0(OCH2Ph), 33.4(BrCH2Ph).Anal. Calcd for C14H13BrO: C, 60.67; H, 4.73. Found: C, 60.46; H, 4.69.
	In hexane; dichloromethane;	Example 57 3-benzyloxybenzylbromide A solution of 3-benzyloxybenzyl alcohol (9.54 g) in methylene chloride (40 ml) with TMSBr (2.5 eq, 13 mL) was heated at reflux for 1 hr. After cooling, the reaction was concentrated and then reconcentrated 2 X with methylene chloride (40 ml). The residue was chromatographed on silica gel eluding first with hexane followed by 10percent methylene chloride in hexane to afford 3-benzyloxybenzyl bromide which solidifies on cooling. 5.75 g m.p. 38°-40°. 1H NMR 500 MHz (CDCl3) d 7.43-7.3 (m, 5H), 7.22 (t, J=8.1 Hz, 1H), 7.0-6.9 (m, 2H), 6.88 (ddd, J=8.1, 2.4, 0.6 Hz), 5.021 (s, 2H), 4.417 (s, 2H)
	In hexane; dichloromethane;	Example 57 3-benzyloxybenzylbromide A solution of 3-benzyloxybenzyl alcohol (2.04 g) in methylene chloride (20 mL) with TMS Bromide (2.5 eq. 3.14 mL) was heated at reflux for 6 hr. After cooling, the reaction was concentrated and then reconcentrated 2* from methylene chloride. The residue was chromatographed on silica gel with 5percent methylene chloride in hexane to afford 3-benzyloxybenzyl bromide (1.26 g) as an oil. 1 H NMR 500 MHz (CDCl3) d 7.43-7.3 (m, 5H), 7.22 (t, J=8.1 Hz, 1H), 7.0-6.9 (m, 2H), 6.88 (ddd, J=8.1, 2.4, 0.6 Hz, 1H), 5.021 (s, 2H), 4.417 (s, 2H)
	In hexane; dichloromethane;	Example 57 3-benzyloxybenzylbromide A solution of 3-benzyloxybenzyl alcohol (9.54 g) in methylene chloride (40 ml) with TMSBr (2.5 eq, 13 mL) was heated at reflux for 1 hr. After cooling, the reaction was concentrated and then reconcentrated 2 * with methylene chloride (40 ml). The residue was chromatographed on silica gel eluding first with hexane followed by 10percent methylene chloride in hexane to afford 3-benzyloxybenzyl bromide which solidifies on cooling. 5.75 g m.p. 38°-40°. 1 H NMR 500 MHz (CDCl3) d 7.43-7.3 (m, 5H), 7.22 (t, J=8.1Hz, 1H), 7.0-6.9 (m, 2H), 6.88 (ddd, J=8.1, 2.4, 0.6 Hz), 5.021 (s, 2H), 4.417 (s, 2H)
	With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 0 - 20℃; for 3h;	Intermediate Ll. b.2 (Scheme 1.1) Step A: l-((3-(Bromomethyl)phenoxy)methyl)benzeneTo a solution of 3-benzyloxybenzyl alcohol (2 g, 9.3 mmol) and carbon tetrabromide (4 g, 12.1 mmol) in CH2Cl2 (70 mL), cooled to O°C, was added a solution of triphenylphosphine (2.9 g, 11.2 mmol) in CH2Cl2 (20 mL). The reaction was stirred at rt for 3 h and concentrated. Purification by flash chromatography (silica gel, 0-8percent EtOAc/hexanes) gave l-((3-(bromomethyl)phenoxy)methyl)benzene. 1H NMR (400 MHz, CDCl3) delta 7.39 (m, 5H), 7.25 (m, 1H), 7.00 (m, 2H), 6.92 (m, 1H), 5.06 (s, 2H), 4.46 (s, 2H).

Reference： [1]Patent: US2003/186943,2003,A1
[2]Patent: US6770658,2004,B2
[3]Journal of Organic Chemistry,2011,vol. 76,p. 6703 - 6714
[4]Journal of Organic Chemistry,1997,vol. 62,p. 6690 - 6691
[5]Patent: US2004/19016,2004,A1 .Location in patent: Page/Page column 43
[6]Journal of Medicinal Chemistry,1993,vol. 36,p. 2950 - 2955
[7]Arzneimittel-Forschung/Drug Research,1997,vol. 47,p. 13 - 18
[8]Journal of Agricultural and Food Chemistry,2000,vol. 48,p. 2547 - 2555
[9]European Journal of Medicinal Chemistry,2011,vol. 46,p. 4227 - 4237
[10]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 2888 - 2902
[11]Journal of Medicinal Chemistry,1996,vol. 39,p. 86 - 95
[12]Journal of the Chemical Society,1965,p. 3645 - 3660
[13]Tetrahedron,1992,vol. 48,p. 819 - 830
[14]Journal of Medicinal Chemistry,1989,vol. 32,p. 1757 - 1763
[15]Journal of Organic Chemistry,1994,vol. 59,p. 5999 - 6007
[16]Bioorganic and Medicinal Chemistry Letters,1996,vol. 6,p. 941 - 944
[17]Bioorganic and Medicinal Chemistry Letters,1998,vol. 8,p. 2447 - 2450
[18]Journal of Medicinal Chemistry,2007,vol. 50,p. 3540 - 3560
[19]Tetrahedron Letters,2006,vol. 47,p. 6281 - 6284
[20]Patent: US6034118,2000,A
[21]Patent: US5705524,1998,A
[22]Patent: US5811450,1998,A
[23]Patent: WO2006/55434,2006,A2 .Location in patent: Page/Page column 52
[24]RSC Advances,2015,vol. 5,p. 82153 - 82158

5
[ 1700-30-7 ]
[ 158585-00-3 ]

Yield	Reaction Conditions	Operation in experiment
55%	With n-butyllithium; BrF₂CH₂CH₂F₂Br In toluene at -20℃;
52%	Stage #1: (3-(benzyloxy)phenyl)methanol With n-butyllithium In toluene at -78 - -5℃; for 1h; Stage #2: With 1,2-dibromo-1,1,2,2-tetrachloroethane In toluene at -78 - 25℃; for 12h;
51%	With n-butyllithium; 1,2-dibromo-1,1,2,2-tetrafluoroethane In toluene at -10℃;

51%

With n-butyllithium; 1,2-dibromo-1,1,2,2-tetrafluoroethane In hexane; toluene 1.) -5 deg C, 6 h, 2.) -78 deg C to room temperature, 16 h;

Reference： [1]Hollinshead; Nichols; Wilson [Journal of Organic Chemistry, 1994, vol. 59, # 22, p. 6703 - 6709]
[2]Henry, Kevin M.; Townsend, Craig A. [Journal of the American Chemical Society, 2005, vol. 127, # 10, p. 3300 - 3309]
[3]Lampe, John W.; Hughes, Philip F.; Biggers, Christopher K.; Smith, Shelley H.; Hu, Hong [Journal of Organic Chemistry, 1994, vol. 59, # 18, p. 5147 - 5148]
[4]Lampe, John W.; Hughes, Philip F.; Biggers, Christopher K.; Smith, Shelley H.; Hu, Hong [Journal of Organic Chemistry, 1996, vol. 61, # 14, p. 4572 - 4581]

6
[ 620-24-6 ]
[ 100-39-0 ]
[ 1700-30-7 ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate In acetone for 7h; Reflux; Inert atmosphere;
95%	With potassium carbonate In acetone for 4h; Heating;
89%	With potassium carbonate In acetone at 45℃; for 12h;	4.1.1. General synthetic procedure for intermediate 2a General procedure: To a solution of 3-hydroxybenzyl alcohol (1 equiv) and bromoalkane(1.02 equiv) in acetone was added K2CO3 (2 equiv) at roomtemperature. The reaction mixture was heated to 45 °C with stirring for12 h. Then the reaction mixture was cooled to room temprature followedby filtration and the filtrate was concentrated under vacuum. Theresidue was purified by silica gel column chromatography using amixture of petroleum ether/ethyl acetate (20:5, v/v) as eluent to afford2a. (3-(benzyloxy)phenyl)methanol. Yield: 89%; colorless oil; 1HNMR (300 MHz, DMSO-d6) δ: 7.48-7.25 (m, 6H), 7.15-7.08 (m, 1H),6.97-6.90 (m, 2H), 5.32 (s, 1H), 5.14 (s, 2H), 4.61 (s, 2H).

89%	With potassium carbonate In N,N-dimethyl-formamide at 0 - 20℃; for 16h;	26.1 (3-(benzyloxy)phenyl)methanol 26b 3-(Light methyl) benzoquinone (1.241 g, 10 mmol) was dissolved in 15 mL of N,N-dimethylformamide and potassium carbonate (4.14 g, 30 mmol) was added.Cold to 0 ° C,Add bromide knot (1.88g, llmmol),The reaction was carried out for 16 hours at room temperature.Add 60 mL of water and stir.Extract with ethyl acetate (60 mL X 2),Combine the organic phase,Dried over anhydrous sodium sulfate and concentrated.The resulting residue was purified by silica gel column chromatography using a solvent system D.The title compound 26b (1.9 g, yield: 89%) was obtained.
75%	With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 24h;
	With sodium hydroxide In methanol Ambient temperature;
	With potassium carbonate In acetone at 45℃; for 12h;

Reference： [1]Location in patent: experimental part Banfi, Luca; Basso, Andrea; Giardini, Lorenzo; Riva, Renata; Rocca, Valeria; Guanti, Giuseppe [European Journal of Organic Chemistry, 2011, # 1, p. 100 - 109]
[2]Lee, Jeewoo; Lee, Ju-Hyun; Kim, Su Yeon; Perry, Nicholas A.; Lewin, Nancy E.; Ayres, Jolene A.; Blumberg, Peter M. [Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 6, p. 2022 - 2031]
[3]Li, Zheng; Chen, Yueming; Zhang, Yuhan; Jiang, Hongwei; Liu, Yanzhi; Chen, Yufang; Zhang, Luyong; Qian, Hai [Bioorganic Chemistry, 2018, vol. 80, p. 296 - 302]
[4]Current Patent Assignee: JIANGSU HENGRUI MEDICINE CO., LTD. - CN110218218, 2019, A Location in patent: Paragraph 0713; 0715-0719
[5]Guanti, Giuseppe; Banfi, Luca; Riva, Renata [Tetrahedron, 1994, vol. 50, # 41, p. 11945 - 11966]
[6]Ma, Dawei; Ma, Zhaochun; Kozikowski, Alan P.; Pshenichkin, Sergey; Wroblewski, Jarda T. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 18, p. 2447 - 2450]
[7]Li, Zheng; Yang, Jianyong; Gu, Weijie; Cao, Guoshen; Fu, Xiaoting; Sun, Xuedan; Zhang, Yu; Jin, Hui; Huang, Wenlong; Qian, Hai [RSC Advances, 2016, vol. 6, # 52, p. 46356 - 46365]

7
[ 91475-97-7 ]
[ 1700-30-7 ]
[ 96995-06-1 ]

Yield	Reaction Conditions	Operation in experiment
1: 20% 2: 47%	With chloro-trimethyl-silane; sodium iodide In acetonitrile at -20℃; for 1.5h;

Reference： [1]Rigby, James H.; Wilson, JoAnn Zbur [Tetrahedron Letters, 1984, vol. 25, # 14, p. 1429 - 1432]

8
[ 620-24-6 ]
[ 100-44-7 ]
[ 1700-30-7 ]

Yield	Reaction Conditions	Operation in experiment
85%	With N-benzyl-trimethylammonium hydroxide; potassium carbonate In methanol; N,N-dimethyl-formamide at 70℃; for 18h;

Reference： [1]Kelley, James L.; Krochmal, Mark P.; Linn, James A.; McLean, Ed W.; Soroko, Francis E. [Journal of Medicinal Chemistry, 1988, vol. 31, # 3, p. 606 - 612]

9
[ 1700-30-7 ]
[ 7377-26-6 ]
4-(2-Benzyloxy-6-hydroxymethyl-benzoyl)-benzoic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
36%	With n-butyllithium In tetrahydrofuran; hexane; toluene 1.) -5 deg C, 6 h, 2.) -78 deg C, 1 h;

Reference： [1]Lampe, John W.; Hughes, Philip F.; Biggers, Christopher K.; Smith, Shelley H.; Hu, Hong [Journal of Organic Chemistry, 1996, vol. 61, # 14, p. 4572 - 4581]

10
[ 1700-30-7 ]
[ 440105-49-7 ]

Yield	Reaction Conditions	Operation in experiment
97%	With diphenylphosphoranyl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene In toluene at 20℃; for 18h;
95%	With diphenyl phosphoryl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene In toluene at 0 - 20℃; for 18h; Inert atmosphere;	1 3-(Benzyloxy)benzyl azide To a stirred solution of 3-benzyloxybenzylalcohol (5.0 g, 23.3 mmol) and diphenylphosphoryl azide (6.03 ml, 28.0 mmol) in drytoluene (40 ml) at 0 oc, under an argon atmosphere, was added 1,8-diazabicyclo[5.4.0]undec-7-ene (3.83 ml, 25.6 mmol). The resulting mixture wasallowed to warm to ambient temperature, and stirred for 18 h. The reaction mixture waswashed with water (2x) and 5% HCI solution (1x), then dried and concentrated underreduced pressure. The crude material was filtered through a short column of silica,eluting with 4/96 ethyl acetate/pentane, to afford 3-(benzyloxy)benzyl azide (5.28 g, 95%)as a clear colourless oil. 1H NMR (200 MHz, CDCb) 8 7.48-7.22 (m, 6H); 6.99-6.86 (m,3H); 5.07 (s, 2H); 4.30 (s, 2H). 13C NMR (50 MHz, CDCI3) 8 159.4, 137.2, 137.0, 130.1,128.8, 128.3, 127.7, 120.9, 114.9, 114.9, 70.3, 54.9. UN=N=N/Cm-1 2101.
	Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 4.5 h / -30 °C / Inert atmosphere 2: sodium azide / N,N-dimethyl-formamide / 17 h / 50 °C / Inert atmosphere

Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 12 h / Cooling with ice 2: sodium azide / N,N-dimethyl-formamide / 12 h / 25 °C

Reference： [1]Bell, Ian M.; Gallicchio, Steven N.; Abrams, Marc; Beese, Lorena S.; Beshore, Douglas C.; Bhimnathwala, Hema; Bogusky, Michael J.; Buser, Carolyn A.; Culberson, J. Christopher; Davide, Joseph; Ellis-Hutchings, Michelle; Fernandes, Christine; Gibbs, Jackson B.; Graham, Samuel L.; Hamilton, Kelly A.; Hartman, George D.; Heimbrook, David C.; Homnick, Carl F.; Huber, Hans E.; Huff, Joel R.; Kassahun, Kelem; Koblan, Kenneth S.; Kohl, Nancy E.; Lobell, Robert B.; Lynch Jr., Joseph J.; Robinson, Ronald; Rodrigues, A. David; Taylor, Jeffrey S.; Walsh, Eileen S.; Williams, Theresa M.; Zartmant, C. Blair [Journal of Medicinal Chemistry, 2002, vol. 45, # 12, p. 2388 - 2409]
[2]Current Patent Assignee: VECTUS BIOSYSTEMS LIMITED - WO2018/53588, 2018, A1 Location in patent: Paragraph 00102
[3]Banfi, Luca; Basso, Andrea; Giardini, Lorenzo; Riva, Renata; Rocca, Valeria; Guanti, Giuseppe [European Journal of Organic Chemistry, 2011, # 1, p. 100 - 109]
[4]Cao, Jiangying; Ma, Chunhua; Zang, Jie; Gao, Shuai; Gao, Qianwen; Kong, Xiujie; Yan, Yugang; Liang, Xuewu; Ding, Qin'ge; Zhao, Chunlong; Wang, Binghe; Xu, Wenfang; Zhang, Yingjie [Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 12, p. 3145 - 3157]

11
[ 1700-30-7 ]
[ 1700-37-4 ]

Yield	Reaction Conditions	Operation in experiment
98.5%	With potassium permanganate; zirconium(IV) oxychloride In tetrahydrofuran at 20℃; for 8h; ultrasonification;
95%	With 1,2-dimethyl-3-[3-(methylsulfinyl)propyl]-1H-imidazolium triflate; oxalyl dichloride; triethylamine In dichloromethane; acetonitrile at -78 - 20℃;
89%	With C₆H₄MoNO₇^(1-)*C₁₉H₄₂N⁽¹⁺⁾; oxygen In water at 100℃; for 18h; Green chemistry; chemoselective reaction;	2.3. General procedure for the catalytic oxidation of alcohols toaldehydes General procedure: A mixture of alcohol (0.75 mmol), and catalyst Mo1 (13 mg,3.0 mol%) taken in 0.5 mL of water was stirred at 100 ° C under oxygenatmosphere (O2 bladder) and the stirring was continued for16-24 h as per requirement. The progress of reaction was monitoredby TLC. After completion of the reaction, ethyl acetate was added to the mixture. The aqueous phase was extracted with ethyl acetate 2-3 times. Then the combined organic extracts were driedover anhydrous sodium sulfate and the solvent was removed under reduced pressure. The crude product so obtained was purified by column chromatography using hexane-ethyl acetate as eluent. While the known products were characterized by spectroscopic techniques and compared with reported data and the new products 22b and 36b were characterized completely. The characterization detail is provided in supporting information section.

86%	With dipotassium peroxodisulfate; V₂O₅/TiO₂ In water; acetonitrile at 80℃; Sealed tube; Green chemistry;
83%	With potassium phosphate; copper(l) iodide; 1,10-Phenanthroline In 1,4-dioxane at 80℃; Schlenk technique;	General Procedure-2 [For the open air oxidation of alcohols to carbonyl compounds; GP-2(method B)]: General procedure: In an oven dried Schlenk tube, were added alcohol 1 (69.0-199.5 mg, 0.5 mmol), CuI (10 mol%)and 1,10-Phenanthroline (20 mol%) and K3PO4 (2 mmol) followed by the addition of dioxane (2mL) at room temperature under open air atmosphere. The stirred reaction mixture was heated inan oil bath at 80 C for 7-48 h. Progress of the reaction was monitored by TLC till the reaction iscompleted. Then, the reaction mixture was cooled to room temperature, quenched with aqueousNH4Cl solution and then extracted with CH2Cl2 (3 10 mL). The organic layer was washed withsaturated NaCl solution, dried (Na2SO4), and filtered. Evaporation of the solvent under reducedpressure and purification of the crude material by silica gel column chromatography (petroleumether/ethyl acetate) furnished the aldehyde/ketone 2 (61-97%).
71%	With oxalyl dichloride; polystyrene bound sulfoxide reagent; triethylamine In dichloromethane at -60 - -40℃; for 2.5h;
56%	With cerium(III) chloride heptahydrate; sodium hydrogencarbonate In acetonitrile at 50℃; for 35h; Irradiation; Sealed tube;	General procedure (GP1) General procedure: A 10 mL glass vial equipped with a teflon-coated stirring bar was charged with benzylic alcohol 1 (0.2 mmol), CeCl3·7H2O (10 mol %), and NaHCO3 (10 mol%). The glass vial was sealed with a PTFE septum. Then, solvent (2 mL) was added and the reaction was opened to air via a needle. The reaction was placed in a pre-programed temperature (50 °C) controlled blue LED reactor (as shown in Figure S1) and the reaction mixture was irradiated with a 455 nm blue LED. After 35-48 hours, the reaction mixture was concentrated under reduced pressure. Product 2 was purified by flash chromatography on silica using hexane and AcOEt.

Reference： [1]Zhang, Wei-Ge; Zhao, Rui; Ren, Jian; Ren, Li-Xiang; Lin, Jin-Guang; Liu, Dai-Lin; Wu, Ying-Liang; Yao, Xin-Sheng [Archiv der Pharmazie, 2007, vol. 340, # 5, p. 244 - 250]
[2]He, Xun; Chan, Tak Hang [Tetrahedron, 2006, vol. 62, # 14, p. 3389 - 3394]
[3]Thiruvengetam, Prabaharan; Chakravarthy, Rajan Deepan; Chand, Dillip Kumar [Journal of Catalysis, 2019, vol. 376, p. 123 - 133]
[4]Upadhyay, Rahul; Kumar, Shashi; Maurya, Sushil K. [ChemCatChem, 2021, vol. 13, # 16, p. 3594 - 3600]
[5]Reddy, Alavala Gopi Krishna; Mahendar, Lodi; Satyanarayana, Gedu [Synthetic Communications, 2014, vol. 44, # 14, p. 2076 - 2087]
[6]Cole, Derek C; Stock, Joseph R; Kappel, Jo Anne [Bioorganic and medicinal chemistry letters, 2002, vol. 12, # 14, p. 1791 - 1793]
[7]König, Burkhard; Kumar, Sumit; Stahl, Jessica; Yatham, Veera Reddy; Yedase, Girish Suresh [Beilstein Journal of Organic Chemistry, 2021, vol. 17, p. 1727 - 1732]

12
[ 1700-30-7 ]
[ 440105-10-2 ]

Yield	Reaction Conditions	Operation in experiment
64%	Stage #1: (3-(benzyloxy)phenyl)methanol With n-butyllithium In tetrahydrofuran; hexane at -20℃; for 7h; Stage #2: With Trimethyl borate In tetrahydrofuran; hexane at 20℃; for 18h; Further stages.;

Reference： [1]Lampe, John W.; Jagdmann Jr., G. Erik; Johnson, Mary George; Lai, Yen-Shi; Lowden, Christopher T.; Lynch, Michael P.; Mendoza, José S.; Murphy, Marcia M.; Wilson, Joseph W.; Ballas, Lawrence M.; Carter, Kiyomi; Biggers, Christopher K.; Darges, James W.; Davis, Jefferson E.; Hubbard, Frederick R.; Stamper, Mark L.; Defauw, Jean M.; Foglesong, Robert J.; Hall, Steven E.; Heerding, Julia M.; Hollinshead, Sean P.; Hu, Hong; Hughes, Philip F. [Journal of Medicinal Chemistry, 2002, vol. 45, # 12, p. 2624 - 2643]

13
[ 1700-30-7 ]
[ 100-83-4 ]
[ 670274-72-3 ]

Yield	Reaction Conditions	Operation in experiment
	With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0℃;

Reference： [1]Renaudet, Olivier; Reymond, Jean-Louis [Organic Letters, 2004, vol. 6, # 3, p. 397 - 400]

14
[ 1700-30-7 ]
[ 98-86-2 ]
3-(3-benzyloxyphenyl)-1-phenyl-1-propanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With potassium hydroxide In 1,4-dioxane at 80℃;
86%	With potassium hydroxide In 1,4-dioxane at 80℃; for 24h;

Reference： [1]Martínez, Ricardo; Brand, Gabriel J.; Ramón, Diego J.; Yus, Miguel [Tetrahedron Letters, 2005, vol. 46, # 21, p. 3683 - 3686]
[2]Martínez, Ricardo; Ramón, Diego J.; Yus, Miguel [Tetrahedron, 2006, vol. 62, # 38, p. 8988 - 9001]

15
[ 1700-30-7 ]
[ 814-49-3 ]
phosphoric acid 3-benzyloxy-benzyl ester diethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%	With dmap; triethylamine In dichloromethane at 0 - 20℃;

Reference： [1]Kishore Kumar; Saenz, David; Lokesh; Natarajan, Amarnath [Tetrahedron Letters, 2006, vol. 47, # 35, p. 6281 - 6284]

16
[ 79678-37-8 ]
[ 1700-30-7 ]

Yield	Reaction Conditions	Operation in experiment
88.9%	With sodium tetrahydroborate; iodine In tetrahydrofuran at 70℃; for 6h;
6.97 g	With lithium aluminium tetrahydride In tetrahydrofuran at 20℃; for 0.166667h; Inert atmosphere;

Reference： [1]Zhang, Wei-Ge; Zhao, Rui; Ren, Jian; Ren, Li-Xiang; Lin, Jin-Guang; Liu, Dai-Lin; Wu, Ying-Liang; Yao, Xin-Sheng [Archiv der Pharmazie, 2007, vol. 340, # 5, p. 244 - 250]
[2]Van Der Kaaden, Marjolein; Breukink, Eefjan; Pieters, Roland J. [Beilstein Journal of Organic Chemistry, 2012, vol. 8, p. 732 - 737]

17
[ 1700-30-7 ]
[ 537674-64-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: PBr₃ / CH₂Cl₂ / 0 °C 2.1: NaH / dimethylformamide 2.2: 28 percent / dimethylformamide 3.1: 88 percent / H₂ / Pd/C / tetrahydrofuran; methanol / 16 h

Reference： [1]Woo, L. W. Lawrence; Bubert, Christian; Sutcliffe, Oliver-B.; Smith, Andrew; Chander, Surinder K.; Mahon, Mary F.; Purohit, Atul; Reed, Michael J.; Potter, Barry V. L. [Journal of Medicinal Chemistry, 2007, vol. 50, # 15, p. 3540 - 3560]

18
[ 1700-30-7 ]
sulfamic acid 3-[(4-cyano-phenyl)-[1,2,4]triazol-4-yl-amino]-methyl}-phenyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: PBr₃ / CH₂Cl₂ / 0 °C 2.1: NaH / dimethylformamide 2.2: 28 percent / dimethylformamide 3.1: 88 percent / H₂ / Pd/C / tetrahydrofuran; methanol / 16 h 4.1: 47 percent / sulfamoyl chloride / N,N-dimethyl-acetamide / 0 °C

Reference： [1]Woo, L. W. Lawrence; Bubert, Christian; Sutcliffe, Oliver-B.; Smith, Andrew; Chander, Surinder K.; Mahon, Mary F.; Purohit, Atul; Reed, Michael J.; Potter, Barry V. L. [Journal of Medicinal Chemistry, 2007, vol. 50, # 15, p. 3540 - 3560]

19
[ 99-06-9 ]
[ 1700-30-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: conc. H₂SO₄ / 12 h / Heating 2: 39.1 g / K₂CO₃ / dimethylformamide / 16 h / 60 °C 3: 88.9 percent / NaBH₄; I₂ / tetrahydrofuran / 6 h / 70 °C
	Multi-step reaction with 3 steps 1: sulfuric acid / 18 h / Reflux 2: potassium carbonate / acetone / 18 h / Reflux 3: lithium aluminium tetrahydride / tetrahydrofuran / 0.17 h / 20 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 45 °C 1.2: 5 h / 60 °C 2.1: lithium aluminium tetrahydride / tetrahydrofuran / 12 h / 0 - 20 °C / Inert atmosphere

Multi-step reaction with 3 steps 1: thionyl chloride / neat liquid / 16 h / 20 °C / Schlenk technique; Inert atmosphere 2: potassium carbonate / N,N-dimethyl-formamide / 16 h / 80 °C / Inert atmosphere; Schlenk technique 3: sodium t-butanolate; 15-crown-5; hydrogen; (1-(2-(2,3-diisopropyl-1-methylguanidino)ethyl)-3-mesityl-1,3-dihydro-2H-imidazol-2-ylidene)copper(I) chloride / 1,4-dioxane / 24 h / 60 °C / Inert atmosphere

Reference： [1]Zhang, Wei-Ge; Zhao, Rui; Ren, Jian; Ren, Li-Xiang; Lin, Jin-Guang; Liu, Dai-Lin; Wu, Ying-Liang; Yao, Xin-Sheng [Archiv der Pharmazie, 2007, vol. 340, # 5, p. 244 - 250]
[2]Van Der Kaaden, Marjolein; Breukink, Eefjan; Pieters, Roland J. [Beilstein Journal of Organic Chemistry, 2012, vol. 8, p. 732 - 737]
[3]Bi, Fangchao; Ji, Shengli; Venter, Henrietta; Liu, Jingru; Semple, Susan J.; Ma, Shutao [Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 5, p. 884 - 891]
[4]Kaicharla, Trinadh; Ngoc, Trung Tran; Teichert, Johannes F.; Tzaras, Dimitrios-Ioannis; Zimmermann, Birte M. [Journal of the American Chemical Society, 2021, vol. 143, # 40, p. 16865 - 16873]

20
[ 1700-30-7 ]
[ 20967-96-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2006,vol. 14,p. 2022 - 2031
[2]Arzneimittel-Forschung/Drug Research,1970,vol. 20,p. 245 - 246

21
[ 1700-30-7 ]
[ 850795-90-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: n-BuLi / toluene / 1 h / -78 - -5 °C 1.2: 52 percent / 1,2-dibromotetrachloroethane / toluene / 12 h / -78 - 25 °C 2.1: 3.5 g / diethyl azodicarboxylate; Ph₃P / tetrahydrofuran / 0.5 h / 25 °C

Reference： [1]Henry, Kevin M.; Townsend, Craig A. [Journal of the American Chemical Society, 2005, vol. 127, # 10, p. 3300 - 3309]

22
[ 100-83-4 ]
[ 1700-30-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triphenylphosphine; diisopropyl azo-dicarboxylate / tetrahydrofuran / 0 °C 2: sodium borohydride / methanol
	Multi-step reaction with 2 steps 1: NaBH₄ / methanol; H₂O / 0 °C 2: NaOH / methanol / Ambient temperature
	Multi-step reaction with 2 steps 1: NaI, K₂CO₃ / ethanol 2: NaBH₄ / propan-2-ol

	Multi-step reaction with 2 steps 1: aq. NaOH 2: NaBH₄
	Multi-step reaction with 2 steps 1: Cs₂CO₃ / acetonitrile / 16 h / Reflux; Inert atmosphere 2: lithium aluminium hydride / tetrahydrofuran / 2 h / 20 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 0.17 h / 20 °C 1.2: 8 h / 20 °C 2.1: sodium tetrahydridoborate / methanol / 0.5 h / 0 °C
	Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 5 h / 80 °C 2: sodium tetrahydridoborate; methanol / 1 h / Cooling with ice
	Multi-step reaction with 2 steps 1: potassium carbonate / acetone / Reflux; Inert atmosphere 2: sodium tetrahydridoborate / methanol / 2 h / 0 - 20 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 0.25 h / 20 °C 1.2: 12 h / 20 °C 2.1: sodium tetrahydridoborate / methanol / 2 h / 0 - 20 °C

Reference： [1]Renaudet, Olivier; Reymond, Jean-Louis [Organic Letters, 2004, vol. 6, # 3, p. 397 - 400]
[2]Ma, Dawei; Ma, Zhaochun; Kozikowski, Alan P.; Pshenichkin, Sergey; Wroblewski, Jarda T. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 18, p. 2447 - 2450]
[3]Yang, Li-Ming; Lin, Shwu-Jiuan; Yang, Tsang-Hsiung; Lee, Kuo-Hsiung [Bioorganic and Medicinal Chemistry Letters, 1996, vol. 6, # 8, p. 941 - 944]
[4]Baxter,I. et al. [Journal of the Chemical Society, 1965, p. 3645 - 3660]
[5]Fournier, Diane; Poirier, Donald [European Journal of Medicinal Chemistry, 2011, vol. 46, # 9, p. 4227 - 4237]
[6]Sayama, Misa; Inoue, Asuka; Nakamura, Sho; Jung, Sejin; Ikubo, Masaya; Otani, Yuko; Uwamizu, Akiharu; Kishi, Takayuki; Makide, Kumiko; Aoki, Junken; Hirokawa, Takatsugu; Ohwada, Tomohiko [Journal of Medicinal Chemistry, 2017, vol. 60, # 14, p. 6384 - 6399]
[7]Cao, Jiangying; Ma, Chunhua; Zang, Jie; Gao, Shuai; Gao, Qianwen; Kong, Xiujie; Yan, Yugang; Liang, Xuewu; Ding, Qin'ge; Zhao, Chunlong; Wang, Binghe; Xu, Wenfang; Zhang, Yingjie [Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 12, p. 3145 - 3157]
[8]Nagasawa, Shota; Fujiki, Shogo; Sasano, Yusuke; Iwabuchi, Yoshiharu [Journal of Organic Chemistry, 2021, vol. 86, # 9, p. 6952 - 6968]
[9]Wang, Hui; Yang, Ren-Yin; Xu, Bo [Chemistry - A European Journal, 2022, vol. 28, # 23]

23
[ 1700-30-7 ]
trans-4-[4-(6-carboxy-2-hydroxyphenyl)benzoyloxy]-3-(4-hydroxybenzamido)pyrrolidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: BuLi / tetrahydrofuran; hexane / 7 h / -20 °C 1.2: 64 percent / trimethylborate / tetrahydrofuran; hexane / 18 h / 20 °C 2.1: 93 percent / Pd(PPh₃)4; Na₂CO₃ / dioxane / 24 h / Heating 3.1: 100 percent / NaBr; TEMPO; NaHCO₃ / CH₂Cl₂; tetrahydrofuran; various solvent(s) / 0.25 h 4.1: 100 percent / aq. sulfamic acid; NaClO₂ / acetonitrile / 0.5 h / 20 °C 5.1: H₂ / Pd(OH)2 / methanol; tetrahydrofuran / 16 h / 20 °C 5.2: TFA / CH₂Cl₂ / 0.05 h

Reference： [1]Lampe, John W.; Jagdmann Jr., G. Erik; Johnson, Mary George; Lai, Yen-Shi; Lowden, Christopher T.; Lynch, Michael P.; Mendoza, José S.; Murphy, Marcia M.; Wilson, Joseph W.; Ballas, Lawrence M.; Carter, Kiyomi; Biggers, Christopher K.; Darges, James W.; Davis, Jefferson E.; Hubbard, Frederick R.; Stamper, Mark L.; Defauw, Jean M.; Foglesong, Robert J.; Hall, Steven E.; Heerding, Julia M.; Hollinshead, Sean P.; Hu, Hong; Hughes, Philip F. [Journal of Medicinal Chemistry, 2002, vol. 45, # 12, p. 2624 - 2643]

24
[ 1700-30-7 ]
[ 104566-43-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 97 percent / diphenylphosphoryl azide; DBU / toluene / 18 h / 20 °C 2: 87 percent / LiAlH₄ / tetrahydrofuran / 0.5 h / 0 °C
	Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 4.5 h / -30 °C / Inert atmosphere 2: sodium azide / N,N-dimethyl-formamide / 17 h / 50 °C / Inert atmosphere 3: water; triphenylphosphine / tetrahydrofuran / 6 h / 65 °C
	Multi-step reaction with 2 steps 1: diphenyl phosphoryl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 18 h / 0 - 20 °C / Inert atmosphere 2: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / -70 - 0 °C / Inert atmosphere

Reference： [1]Bell, Ian M.; Gallicchio, Steven N.; Abrams, Marc; Beese, Lorena S.; Beshore, Douglas C.; Bhimnathwala, Hema; Bogusky, Michael J.; Buser, Carolyn A.; Culberson, J. Christopher; Davide, Joseph; Ellis-Hutchings, Michelle; Fernandes, Christine; Gibbs, Jackson B.; Graham, Samuel L.; Hamilton, Kelly A.; Hartman, George D.; Heimbrook, David C.; Homnick, Carl F.; Huber, Hans E.; Huff, Joel R.; Kassahun, Kelem; Koblan, Kenneth S.; Kohl, Nancy E.; Lobell, Robert B.; Lynch Jr., Joseph J.; Robinson, Ronald; Rodrigues, A. David; Taylor, Jeffrey S.; Walsh, Eileen S.; Williams, Theresa M.; Zartmant, C. Blair [Journal of Medicinal Chemistry, 2002, vol. 45, # 12, p. 2388 - 2409]
[2]Banfi, Luca; Basso, Andrea; Giardini, Lorenzo; Riva, Renata; Rocca, Valeria; Guanti, Giuseppe [European Journal of Organic Chemistry, 2011, # 1, p. 100 - 109]
[3]Current Patent Assignee: VECTUS BIOSYSTEMS LIMITED - WO2018/53588, 2018, A1

25
[ 1700-30-7 ]
[ 440105-82-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: 97 percent / diphenylphosphoryl azide; DBU / toluene / 18 h / 20 °C 2: 87 percent / LiAlH₄ / tetrahydrofuran / 0.5 h / 0 °C 3: 98 percent / PyBOP; DIEA / CH₂Cl₂ / 18 h 4: 100 percent / 18 h 5: 96 percent / LiN(SiMe₃)2 / tetrahydrofuran / 2 h / 0 °C 6: 92 percent / H₂ / 20percent Pd(OH)2/C / ethanol / 18 h / 20 °C / 760.05 Torr

Reference： [1]Bell, Ian M.; Gallicchio, Steven N.; Abrams, Marc; Beese, Lorena S.; Beshore, Douglas C.; Bhimnathwala, Hema; Bogusky, Michael J.; Buser, Carolyn A.; Culberson, J. Christopher; Davide, Joseph; Ellis-Hutchings, Michelle; Fernandes, Christine; Gibbs, Jackson B.; Graham, Samuel L.; Hamilton, Kelly A.; Hartman, George D.; Heimbrook, David C.; Homnick, Carl F.; Huber, Hans E.; Huff, Joel R.; Kassahun, Kelem; Koblan, Kenneth S.; Kohl, Nancy E.; Lobell, Robert B.; Lynch Jr., Joseph J.; Robinson, Ronald; Rodrigues, A. David; Taylor, Jeffrey S.; Walsh, Eileen S.; Williams, Theresa M.; Zartmant, C. Blair [Journal of Medicinal Chemistry, 2002, vol. 45, # 12, p. 2388 - 2409]

26
[ 1700-30-7 ]
(S)-3-[(tert-butoxycarbonyl)amino]-1-(3-hydroxybenzyl)-2-oxopyrrolidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: 97 percent / diphenylphosphoryl azide; DBU / toluene / 18 h / 20 °C 2: 87 percent / LiAlH₄ / tetrahydrofuran / 0.5 h / 0 °C 3: PyBOP; DIEA / CH₂Cl₂ 4: LiN(SiMe₃)2 / tetrahydrofuran / 0 °C 5: H₂ / 20percent Pd(OH)2/C / ethanol / 20 °C / 760.05 Torr

Reference： [1]Bell, Ian M.; Gallicchio, Steven N.; Abrams, Marc; Beese, Lorena S.; Beshore, Douglas C.; Bhimnathwala, Hema; Bogusky, Michael J.; Buser, Carolyn A.; Culberson, J. Christopher; Davide, Joseph; Ellis-Hutchings, Michelle; Fernandes, Christine; Gibbs, Jackson B.; Graham, Samuel L.; Hamilton, Kelly A.; Hartman, George D.; Heimbrook, David C.; Homnick, Carl F.; Huber, Hans E.; Huff, Joel R.; Kassahun, Kelem; Koblan, Kenneth S.; Kohl, Nancy E.; Lobell, Robert B.; Lynch Jr., Joseph J.; Robinson, Ronald; Rodrigues, A. David; Taylor, Jeffrey S.; Walsh, Eileen S.; Williams, Theresa M.; Zartmant, C. Blair [Journal of Medicinal Chemistry, 2002, vol. 45, # 12, p. 2388 - 2409]

27
[ 1700-30-7 ]
(R)-3-amino-1-(3-hydroxybenzyl)-2-oxopyrrolidine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: 97 percent / diphenylphosphoryl azide; DBU / toluene / 18 h / 20 °C 2: 87 percent / LiAlH₄ / tetrahydrofuran / 0.5 h / 0 °C 3: 98 percent / PyBOP; DIEA / CH₂Cl₂ / 18 h 4: 100 percent / 18 h 5: 96 percent / LiN(SiMe₃)2 / tetrahydrofuran / 2 h / 0 °C 6: 92 percent / H₂ / 20percent Pd(OH)2/C / ethanol / 18 h / 20 °C / 760.05 Torr 7: 100 percent / HCl(gas) / ethyl acetate / 0.25 h / 0 °C

Reference： [1]Bell, Ian M.; Gallicchio, Steven N.; Abrams, Marc; Beese, Lorena S.; Beshore, Douglas C.; Bhimnathwala, Hema; Bogusky, Michael J.; Buser, Carolyn A.; Culberson, J. Christopher; Davide, Joseph; Ellis-Hutchings, Michelle; Fernandes, Christine; Gibbs, Jackson B.; Graham, Samuel L.; Hamilton, Kelly A.; Hartman, George D.; Heimbrook, David C.; Homnick, Carl F.; Huber, Hans E.; Huff, Joel R.; Kassahun, Kelem; Koblan, Kenneth S.; Kohl, Nancy E.; Lobell, Robert B.; Lynch Jr., Joseph J.; Robinson, Ronald; Rodrigues, A. David; Taylor, Jeffrey S.; Walsh, Eileen S.; Williams, Theresa M.; Zartmant, C. Blair [Journal of Medicinal Chemistry, 2002, vol. 45, # 12, p. 2388 - 2409]

28
[ 1700-30-7 ]
(S)-3-amino-1-(3-hydroxybenzyl)-2-oxopyrrolidine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: 97 percent / diphenylphosphoryl azide; DBU / toluene / 18 h / 20 °C 2: 87 percent / LiAlH₄ / tetrahydrofuran / 0.5 h / 0 °C 3: PyBOP; DIEA / CH₂Cl₂ 4: LiN(SiMe₃)2 / tetrahydrofuran / 0 °C 5: H₂ / 20percent Pd(OH)2/C / ethanol / 20 °C / 760.05 Torr 6: HCl(gas) / ethyl acetate / 0 °C

Reference： [1]Bell, Ian M.; Gallicchio, Steven N.; Abrams, Marc; Beese, Lorena S.; Beshore, Douglas C.; Bhimnathwala, Hema; Bogusky, Michael J.; Buser, Carolyn A.; Culberson, J. Christopher; Davide, Joseph; Ellis-Hutchings, Michelle; Fernandes, Christine; Gibbs, Jackson B.; Graham, Samuel L.; Hamilton, Kelly A.; Hartman, George D.; Heimbrook, David C.; Homnick, Carl F.; Huber, Hans E.; Huff, Joel R.; Kassahun, Kelem; Koblan, Kenneth S.; Kohl, Nancy E.; Lobell, Robert B.; Lynch Jr., Joseph J.; Robinson, Ronald; Rodrigues, A. David; Taylor, Jeffrey S.; Walsh, Eileen S.; Williams, Theresa M.; Zartmant, C. Blair [Journal of Medicinal Chemistry, 2002, vol. 45, # 12, p. 2388 - 2409]

29
[ 1700-30-7 ]
2-Fluoro-4-(5-[(Z)-(R)-1-(3-hydroxy-benzyl)-2-oxo-pyrrolidin-3-ylimino]-methyl}-imidazol-1-ylmethyl)-benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1: 97 percent / diphenylphosphoryl azide; DBU / toluene / 18 h / 20 °C 2: 87 percent / LiAlH₄ / tetrahydrofuran / 0.5 h / 0 °C 3: 98 percent / PyBOP; DIEA / CH₂Cl₂ / 18 h 4: 100 percent / 18 h 5: 96 percent / LiN(SiMe₃)2 / tetrahydrofuran / 2 h / 0 °C 6: 92 percent / H₂ / 20percent Pd(OH)2/C / ethanol / 18 h / 20 °C / 760.05 Torr 7: 100 percent / HCl(gas) / ethyl acetate / 0.25 h / 0 °C 8: DIEA / methanol / 1 h / 20 °C / pH 5

Reference： [1]Bell, Ian M.; Gallicchio, Steven N.; Abrams, Marc; Beese, Lorena S.; Beshore, Douglas C.; Bhimnathwala, Hema; Bogusky, Michael J.; Buser, Carolyn A.; Culberson, J. Christopher; Davide, Joseph; Ellis-Hutchings, Michelle; Fernandes, Christine; Gibbs, Jackson B.; Graham, Samuel L.; Hamilton, Kelly A.; Hartman, George D.; Heimbrook, David C.; Homnick, Carl F.; Huber, Hans E.; Huff, Joel R.; Kassahun, Kelem; Koblan, Kenneth S.; Kohl, Nancy E.; Lobell, Robert B.; Lynch Jr., Joseph J.; Robinson, Ronald; Rodrigues, A. David; Taylor, Jeffrey S.; Walsh, Eileen S.; Williams, Theresa M.; Zartmant, C. Blair [Journal of Medicinal Chemistry, 2002, vol. 45, # 12, p. 2388 - 2409]

30
[ 1700-30-7 ]
2-Fluoro-4-(5-[(Z)-(S)-1-(3-hydroxy-benzyl)-2-oxo-pyrrolidin-3-ylimino]-methyl}-imidazol-1-ylmethyl)-benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1: 97 percent / diphenylphosphoryl azide; DBU / toluene / 18 h / 20 °C 2: 87 percent / LiAlH₄ / tetrahydrofuran / 0.5 h / 0 °C 3: PyBOP; DIEA / CH₂Cl₂ 4: LiN(SiMe₃)2 / tetrahydrofuran / 0 °C 5: H₂ / 20percent Pd(OH)2/C / ethanol / 20 °C / 760.05 Torr 6: HCl(gas) / ethyl acetate / 0 °C 7: DIEA / methanol / 20 °C / pH 5

Reference： [1]Bell, Ian M.; Gallicchio, Steven N.; Abrams, Marc; Beese, Lorena S.; Beshore, Douglas C.; Bhimnathwala, Hema; Bogusky, Michael J.; Buser, Carolyn A.; Culberson, J. Christopher; Davide, Joseph; Ellis-Hutchings, Michelle; Fernandes, Christine; Gibbs, Jackson B.; Graham, Samuel L.; Hamilton, Kelly A.; Hartman, George D.; Heimbrook, David C.; Homnick, Carl F.; Huber, Hans E.; Huff, Joel R.; Kassahun, Kelem; Koblan, Kenneth S.; Kohl, Nancy E.; Lobell, Robert B.; Lynch Jr., Joseph J.; Robinson, Ronald; Rodrigues, A. David; Taylor, Jeffrey S.; Walsh, Eileen S.; Williams, Theresa M.; Zartmant, C. Blair [Journal of Medicinal Chemistry, 2002, vol. 45, # 12, p. 2388 - 2409]

31
[ 1700-30-7 ]
C₂₄H₂₃N₅O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 10 steps 1: 97 percent / diphenylphosphoryl azide; DBU / toluene / 18 h / 20 °C 2: 87 percent / LiAlH₄ / tetrahydrofuran / 0.5 h / 0 °C 3: 98 percent / PyBOP; DIEA / CH₂Cl₂ / 18 h 4: 100 percent / 18 h 5: 96 percent / LiN(SiMe₃)2 / tetrahydrofuran / 2 h / 0 °C 6: 92 percent / H₂ / 20percent Pd(OH)2/C / ethanol / 18 h / 20 °C / 760.05 Torr 7: 100 percent / HCl(gas) / ethyl acetate / 0.25 h / 0 °C 8: DIEA / methanol / 20 °C / pH 5 9: NaCNBH₃ / methanol / 20 °C 10: Cs₂CO₃ / dimethylformamide / 50 °C

Reference： [1]Bell, Ian M.; Gallicchio, Steven N.; Abrams, Marc; Beese, Lorena S.; Beshore, Douglas C.; Bhimnathwala, Hema; Bogusky, Michael J.; Buser, Carolyn A.; Culberson, J. Christopher; Davide, Joseph; Ellis-Hutchings, Michelle; Fernandes, Christine; Gibbs, Jackson B.; Graham, Samuel L.; Hamilton, Kelly A.; Hartman, George D.; Heimbrook, David C.; Homnick, Carl F.; Huber, Hans E.; Huff, Joel R.; Kassahun, Kelem; Koblan, Kenneth S.; Kohl, Nancy E.; Lobell, Robert B.; Lynch Jr., Joseph J.; Robinson, Ronald; Rodrigues, A. David; Taylor, Jeffrey S.; Walsh, Eileen S.; Williams, Theresa M.; Zartmant, C. Blair [Journal of Medicinal Chemistry, 2002, vol. 45, # 12, p. 2388 - 2409]

32
[ 1700-30-7 ]
(20S)-19,20,21,22-tetrahydro-19-oxo-17H-18,20-ethano-6,10:12,16-dimetheno-16H-imidazo[3,4-h][1,8,11,14]oxatriazacycloeicosine-9-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 10 steps 1: 97 percent / diphenylphosphoryl azide; DBU / toluene / 18 h / 20 °C 2: 87 percent / LiAlH₄ / tetrahydrofuran / 0.5 h / 0 °C 3: PyBOP; DIEA / CH₂Cl₂ 4: LiN(SiMe₃)2 / tetrahydrofuran / 0 °C 5: H₂ / 20percent Pd(OH)2/C / ethanol / 20 °C / 760.05 Torr 6: HCl(gas) / ethyl acetate / 0 °C 7: DIEA / methanol / 20 °C / pH 5 8: NaCNBH₃ / methanol / 20 °C 9: 76 percent / Cs₂CO₃ / dimethylformamide / 50 °C

Reference： [1]Bell, Ian M.; Gallicchio, Steven N.; Abrams, Marc; Beese, Lorena S.; Beshore, Douglas C.; Bhimnathwala, Hema; Bogusky, Michael J.; Buser, Carolyn A.; Culberson, J. Christopher; Davide, Joseph; Ellis-Hutchings, Michelle; Fernandes, Christine; Gibbs, Jackson B.; Graham, Samuel L.; Hamilton, Kelly A.; Hartman, George D.; Heimbrook, David C.; Homnick, Carl F.; Huber, Hans E.; Huff, Joel R.; Kassahun, Kelem; Koblan, Kenneth S.; Kohl, Nancy E.; Lobell, Robert B.; Lynch Jr., Joseph J.; Robinson, Ronald; Rodrigues, A. David; Taylor, Jeffrey S.; Walsh, Eileen S.; Williams, Theresa M.; Zartmant, C. Blair [Journal of Medicinal Chemistry, 2002, vol. 45, # 12, p. 2388 - 2409]

33
[ 1700-30-7 ]
2-Fluoro-4-[1-(5-[(Z)-(R)-1-(3-hydroxy-benzyl)-2-oxo-pyrrolidin-3-ylimino]-methyl}-imidazol-1-yl)-ethyl]-benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1: 97 percent / diphenylphosphoryl azide; DBU / toluene / 18 h / 20 °C 2: 87 percent / LiAlH₄ / tetrahydrofuran / 0.5 h / 0 °C 3: 98 percent / PyBOP; DIEA / CH₂Cl₂ / 18 h 4: 100 percent / 18 h 5: 96 percent / LiN(SiMe₃)2 / tetrahydrofuran / 2 h / 0 °C 6: 92 percent / H₂ / 20percent Pd(OH)2/C / ethanol / 18 h / 20 °C / 760.05 Torr 7: 100 percent / HCl(gas) / ethyl acetate / 0.25 h / 0 °C 8: DIEA / methanol / 20 °C / pH 5

Reference： [1]Bell, Ian M.; Gallicchio, Steven N.; Abrams, Marc; Beese, Lorena S.; Beshore, Douglas C.; Bhimnathwala, Hema; Bogusky, Michael J.; Buser, Carolyn A.; Culberson, J. Christopher; Davide, Joseph; Ellis-Hutchings, Michelle; Fernandes, Christine; Gibbs, Jackson B.; Graham, Samuel L.; Hamilton, Kelly A.; Hartman, George D.; Heimbrook, David C.; Homnick, Carl F.; Huber, Hans E.; Huff, Joel R.; Kassahun, Kelem; Koblan, Kenneth S.; Kohl, Nancy E.; Lobell, Robert B.; Lynch Jr., Joseph J.; Robinson, Ronald; Rodrigues, A. David; Taylor, Jeffrey S.; Walsh, Eileen S.; Williams, Theresa M.; Zartmant, C. Blair [Journal of Medicinal Chemistry, 2002, vol. 45, # 12, p. 2388 - 2409]

34
[ 1700-30-7 ]
[ 330213-78-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1: 97 percent / diphenylphosphoryl azide; DBU / toluene / 18 h / 20 °C 2: 87 percent / LiAlH₄ / tetrahydrofuran / 0.5 h / 0 °C 3: 98 percent / PyBOP; DIEA / CH₂Cl₂ / 18 h 4: 100 percent / 18 h 5: 96 percent / LiN(SiMe₃)2 / tetrahydrofuran / 2 h / 0 °C 6: 92 percent / H₂ / 20percent Pd(OH)2/C / ethanol / 18 h / 20 °C / 760.05 Torr 7: 100 percent / HCl(gas) / ethyl acetate / 0.25 h / 0 °C 8: DIEA / methanol / 1 h / 20 °C / pH 5 9: NaCNBH₃ / methanol / 18 h / 20 °C

Reference： [1]Bell, Ian M.; Gallicchio, Steven N.; Abrams, Marc; Beese, Lorena S.; Beshore, Douglas C.; Bhimnathwala, Hema; Bogusky, Michael J.; Buser, Carolyn A.; Culberson, J. Christopher; Davide, Joseph; Ellis-Hutchings, Michelle; Fernandes, Christine; Gibbs, Jackson B.; Graham, Samuel L.; Hamilton, Kelly A.; Hartman, George D.; Heimbrook, David C.; Homnick, Carl F.; Huber, Hans E.; Huff, Joel R.; Kassahun, Kelem; Koblan, Kenneth S.; Kohl, Nancy E.; Lobell, Robert B.; Lynch Jr., Joseph J.; Robinson, Ronald; Rodrigues, A. David; Taylor, Jeffrey S.; Walsh, Eileen S.; Williams, Theresa M.; Zartmant, C. Blair [Journal of Medicinal Chemistry, 2002, vol. 45, # 12, p. 2388 - 2409]

35
[ 1700-30-7 ]
(S)-2-fluoro-4-(5-[1-(3-hydroxybenzyl)-2-oxopyrrolidin-3-ylamino]methyl}imidazol-1-ylmethyl)benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1: 97 percent / diphenylphosphoryl azide; DBU / toluene / 18 h / 20 °C 2: 87 percent / LiAlH₄ / tetrahydrofuran / 0.5 h / 0 °C 3: PyBOP; DIEA / CH₂Cl₂ 4: LiN(SiMe₃)2 / tetrahydrofuran / 0 °C 5: H₂ / 20percent Pd(OH)2/C / ethanol / 20 °C / 760.05 Torr 6: HCl(gas) / ethyl acetate / 0 °C 7: DIEA / methanol / 20 °C / pH 5 8: NaCNBH₃ / methanol / 20 °C

Reference： [1]Bell, Ian M.; Gallicchio, Steven N.; Abrams, Marc; Beese, Lorena S.; Beshore, Douglas C.; Bhimnathwala, Hema; Bogusky, Michael J.; Buser, Carolyn A.; Culberson, J. Christopher; Davide, Joseph; Ellis-Hutchings, Michelle; Fernandes, Christine; Gibbs, Jackson B.; Graham, Samuel L.; Hamilton, Kelly A.; Hartman, George D.; Heimbrook, David C.; Homnick, Carl F.; Huber, Hans E.; Huff, Joel R.; Kassahun, Kelem; Koblan, Kenneth S.; Kohl, Nancy E.; Lobell, Robert B.; Lynch Jr., Joseph J.; Robinson, Ronald; Rodrigues, A. David; Taylor, Jeffrey S.; Walsh, Eileen S.; Williams, Theresa M.; Zartmant, C. Blair [Journal of Medicinal Chemistry, 2002, vol. 45, # 12, p. 2388 - 2409]

36
[ 1700-30-7 ]
2-Fluoro-4-[1-(5-[(R)-1-(3-hydroxy-benzyl)-2-oxo-pyrrolidin-3-ylamino]-methyl}-imidazol-1-yl)-ethyl]-benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1: 97 percent / diphenylphosphoryl azide; DBU / toluene / 18 h / 20 °C 2: 87 percent / LiAlH₄ / tetrahydrofuran / 0.5 h / 0 °C 3: 98 percent / PyBOP; DIEA / CH₂Cl₂ / 18 h 4: 100 percent / 18 h 5: 96 percent / LiN(SiMe₃)2 / tetrahydrofuran / 2 h / 0 °C 6: 92 percent / H₂ / 20percent Pd(OH)2/C / ethanol / 18 h / 20 °C / 760.05 Torr 7: 100 percent / HCl(gas) / ethyl acetate / 0.25 h / 0 °C 8: DIEA / methanol / 20 °C / pH 5 9: NaCNBH₃ / methanol / 20 °C

Reference： [1]Bell, Ian M.; Gallicchio, Steven N.; Abrams, Marc; Beese, Lorena S.; Beshore, Douglas C.; Bhimnathwala, Hema; Bogusky, Michael J.; Buser, Carolyn A.; Culberson, J. Christopher; Davide, Joseph; Ellis-Hutchings, Michelle; Fernandes, Christine; Gibbs, Jackson B.; Graham, Samuel L.; Hamilton, Kelly A.; Hartman, George D.; Heimbrook, David C.; Homnick, Carl F.; Huber, Hans E.; Huff, Joel R.; Kassahun, Kelem; Koblan, Kenneth S.; Kohl, Nancy E.; Lobell, Robert B.; Lynch Jr., Joseph J.; Robinson, Ronald; Rodrigues, A. David; Taylor, Jeffrey S.; Walsh, Eileen S.; Williams, Theresa M.; Zartmant, C. Blair [Journal of Medicinal Chemistry, 2002, vol. 45, # 12, p. 2388 - 2409]

37
[ 1700-30-7 ]
HO-(2,6-naphthylidene)-C(NH)NHC(O)OCH₂-(p-C₆H₄)-OCH₂C(O)NHCH₂-(polystyrene resin) [ No CAS ]
[ 20967-96-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2001,vol. 11,p. 2205 - 2208

38
[ 1700-30-7 ]
[ 587-33-7 ]

Reference： [1]Journal of Organic Chemistry,1997,vol. 62,p. 6690 - 6691

39
[ 1700-30-7 ]
(+/-)-trans-2-(3'-hydroxybenzyl)-3-<3'',4''-(methylenedioxy)benzyl>butyrolactone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 53 percent / Ph₃P, Br₂, pyridine / acetonitrile / 0.5 h / 50 °C 2: HMPA / tetrahydrofuran; hexane / -78 - 20 °C 3: 90 percent / W-2 Raney Ni / ethanol / 2 h / Heating

Reference： [1]Eich, Eckart; Pertz, Heinz; Kaloga, Macki; Schulz, Jutta; Fesen, Mark R.; Mazumder, Abhijit; Pommier, Yves [Journal of Medicinal Chemistry, 1996, vol. 39, # 1, p. 86 - 95]

40
[ 1700-30-7 ]
(+/-)-trans-2-(3'-hydroxybenzyl)-3-(3'',4''-dimethoxybenzyl)butyrolactone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 53 percent / Ph₃P, Br₂, pyridine / acetonitrile / 0.5 h / 50 °C 2: HMPA / tetrahydrofuran; hexane / -78 - 20 °C 3: W-2 Raney Ni / ethanol / 2 h / Heating

Reference： [1]Eich, Eckart; Pertz, Heinz; Kaloga, Macki; Schulz, Jutta; Fesen, Mark R.; Mazumder, Abhijit; Pommier, Yves [Journal of Medicinal Chemistry, 1996, vol. 39, # 1, p. 86 - 95]

41
[ 1700-30-7 ]
(-)-enterolactone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: PBr₃ / diethyl ether / 3 h / Ambient temperature 2: 1.) n-BuLi, 2.) TMEDA / 1.) THF, hexane, -20 deg C, 90 min; -80 deg C, 2 h, 2.) -20 deg C, 16 h 3: 62 percent / NiCl₂*6H₂O, NaBH₄, 2 N aq. KOH / tetrahydrofuran; methanol 4: 82 percent / H₂ / 5percent Pd/C / ethyl acetate / 16 h / Ambient temperature

Reference： [1]Van Oeveren; Jansen; Feringa [Journal of Organic Chemistry, 1994, vol. 59, # 20, p. 5999 - 6007]

42
[ 1700-30-7 ]
Enterodiol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: PBr₃ / diethyl ether / 3 h / Ambient temperature 2: 1.) n-BuLi, 2.) TMEDA / 1.) THF, hexane, -20 deg C, 90 min; -80 deg C, 2 h, 2.) -20 deg C, 16 h 3: 62 percent / NiCl₂*6H₂O, NaBH₄, 2 N aq. KOH / tetrahydrofuran; methanol 4: 82 percent / H₂ / 5percent Pd/C / ethyl acetate / 16 h / Ambient temperature 5: 87 percent / LiAlH₄ / tetrahydrofuran

Reference： [1]Van Oeveren; Jansen; Feringa [Journal of Organic Chemistry, 1994, vol. 59, # 20, p. 5999 - 6007]

43
[ 1700-30-7 ]
[ 160721-28-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 73 percent / 50 percent NaOH, n-Bu₄N⁽¹⁺⁾*HSO₄^(1-) / benzene; H₂O / Ambient temperature 2: conc. H₂SO₄ / 2 h / Heating 3: hydrogen / Pd/C / aq. ethanol / 1.5 h
	Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 1 h / 0 °C 2: sodium hydride / N,N-dimethyl-formamide; mineral oil / 2 h / 50 °C 3: hydrogen; palladium 10% on activated carbon / methanol / 1 h / 20 °C

Reference： [1]Guanti, Giuseppe; Banfi, Luca; Riva, Renata [Tetrahedron, 1994, vol. 50, # 41, p. 11945 - 11966]
[2]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP2623492, 2013, A1

44
[ 1700-30-7 ]
[ 135203-60-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 85 percent / PBr₃ / CH₂Cl₂ / 3 h / 0 - 23 °C 2: 85 percent / tetrabutylammonium iodide / 10 h / 110 - 130 °C
	Multi-step reaction with 2 steps 1: phosphorus tribromide / dichloromethane / 2 h / 20 °C 2: tetrabutylammomium bromide / 4 h / 125 °C

Reference： [1]Thakkar, Kshitij; Geahlen, Robert L.; Cushman, Mark [Journal of Medicinal Chemistry, 1993, vol. 36, # 20, p. 2950 - 2955]
[2]Hu, Wei-Ping; Cao, Guo-Dong; Zhu, Jin-Hua; Li, Jia-Zhong; Liu, Xiu-Hua [RSC Advances, 2015, vol. 5, # 100, p. 82153 - 82158]

45
[ 1700-30-7 ]
3-(6-Dimethylamino-2-trifluoromethyl-purin-9-ylmethyl)-phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: PBr₃ / toluene / 0.17 h / 100 °C 2: 58 percent / K₂CO₃ / dimethylformamide / 48 h 3: 51 percent / H₂ / 5percent Pd/C / acetic acid; methanol / 2 h / 1520 - 2280 Torr

Reference： [1]Kelley; Linn; Selway [Journal of Medicinal Chemistry, 1989, vol. 32, # 8, p. 1757 - 1763]

46
[ 1700-30-7 ]
[ 50765-13-4 ]

Yield	Reaction Conditions	Operation in experiment
99%	With iodine; silver trifluoroacetate In chloroform at 20℃; for 1h;
96%	With silver trifluoroacetate In chloroform at 20℃; for 1h;
71%	With Iodine monochloride; sodium hydrogencarbonate In methanol; dichloromethane at 0 - 20℃; for 1h;	Acetic acid 5-benzyloxy-2-iodo-benzyl ester. To a well stirred solution of 3-benzyloxybenzyl alcohol (5.5 g, 25.7 mmol) in methanol (100 mL) and sodium hydrogencarbonate (8.4 g, 100 mmol) was added a 1.0 M solution of iodine monochloride in dichloromathane (30 mL) at 0° C. The reaction mixture was brought to room temperature and stirring continued for additional 1 h. The reaction mixture was concentrated and then diluted with dicholomethane (150 mL), washed with 10% aqueous sodium thiosulfate and dried (Na2SO4). The desired compound was purified by flash chromatography (silica) using 20% ethyl acetate in hexane to give 5-benzyloxy-2-iodobenzyl alcohol (6.2 g, 71% yield). The alcohol (4.2 g, 12.4 mmol) was dissolved in dichloromethane (100 mL) added acetic anhydride (2.52 g, 24.7 mmol) and catalytic amount of 4-dimethylaminopyridine. The reaction mixture was then stirred for 12 h, washed with aqueous sodium hydrogencarbonate and then dried (Na2SO4) to give acetic acid 5-benzyloxy-2-iodo-benzyl ester in quantitative yield. MS (ESI) 405 (M+Na); Rf=2.27.

71%	With Iodine monochloride; sodium hydrogencarbonate In methanol; dichloromethane at 0 - 20℃; for 1h;	Acetic acid 5-benzyloxy-2-iodo-benzyl ester; To a well stirred solution of 3-benzyloxybenzyl alcohol (5.5 g, 25.7 mmol) in methanol (100 mL) and sodium hydrogencarbonate (8.4 g, 100 mmol) was added a 1.0 M solution of iodine monochloride in dichloromathane (30 mL) at 0° C. The reaction mixture was brought to room temperature and stirring continued for additional 1 h. The reaction mixture was concentrated and then diluted with dicholomethane (150 mL), washed with 10% aqueous sodium thiosulfate and dried (Na2SO4). The desired compound was purified by flash chromatography (silica) using 20% ethyl acetate in hexane to give 5-benzyloxy-2-iodobenzyl alcohol (6.2 g, 71% yield). The alcohol (4.2 g, 12.4 mmol) was dissolved in dichloromethane (100 mL) added acetic anhydride (2.52 g, 24.7 mmol) and catalytic amount of 4-dimethylaminopyridine. The reaction mixture was then stirred for 12 h, washed with aqueous sodium hydrogencarbonate and then dried (Na2SO4) to give acetic acid 5-benzyloxy-2-iodo-benzyl ester in quantitative yield. MS (ESI) 405 (M+Na); Rf=2.27.
	With iodine; silver trifluoroacetate In chloroform at 22℃; for 2.16667h; Inert atmosphere;
	With iodine; silver trifluoroacetate In chloroform at 20℃; for 2h; Inert atmosphere;

Reference： [1]Coya, Estibaliz; Sotomayor, Nuria; Lete, Esther [Advanced Synthesis and Catalysis, 2015, vol. 357, # 14-15, p. 3206 - 3214]
[2]Van Der Kaaden, Marjolein; Breukink, Eefjan; Pieters, Roland J. [Beilstein Journal of Organic Chemistry, 2012, vol. 8, p. 732 - 737]
[3]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US2006/94707, 2006, A1 Location in patent: Page/Page column 27
[4]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US2007/259850, 2007, A1 Location in patent: Page/Page column 64 Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US2007/259851, 2007, A1 Location in patent: Page/Page column 64
[5]Fan, Yi Chiao; Kwon, Ohyun [Organic Letters, 2012, vol. 14, # 13, p. 3264 - 3267]
[6]Wang, Liang; Li, Xuehu; Tao, Hua; Zhou, Xiang; Lu, Xihong; Du, Wenyue; Jiang, Tingting; Xin, Zhijun; Liang, Jianping [Organic and Biomolecular Chemistry, 2017, vol. 15, # 11, p. 2403 - 2410]

47
cis 1-chlorocarbonyl-2,6-dimethyl-4-tert-butoxycarbonylpiperazine [ No CAS ]
[ 1700-30-7 ]
3-Benzyloxybenzyl cis-2,6-dimethylpiperazine-1-carboxylate hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%		79 Example 79 Example 79 3-Benzyloxybenzyl cis-2,6-dimethylpiperazine-1-carboxylate hydrochloride was prepared from cis 1-chlorocarbonyl-2,6-dimethyl-4-tert-butoxycarbonylpiperazine and 3-benzyloxybenzyl alcohol according to the methods described for Examples 52 and 54 to give the product as a white solid (0.254 g, 65% overall); νmax (nujol)/cm-1 3320, 2684, 2587, 1716, 1694, 1599, 1415, and 1312; δH (400 MHz, DMSO-d6) 10.02 (1H, br), 9.27 (1H, br), 7.45-7.28 (6H, m), 7.01-6.94 (3H, m), 5.11 (2H, s), 5.09 (2H, s), 4.33 (2H, m), 3.15 (2H, d, J 13.2 Hz), 3.07 (2H, m), and 1.31 (6H, d, J 7.6 Hz).

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG; LIGAND PHARMACEUTICALS INC - US2002/143020, 2002, A1

48
[ 1700-30-7 ]
[ 6674-22-2 ]
[ 440105-49-7 ]

Yield	Reaction Conditions	Operation in experiment
	With diphenylphosphoranyl azide In toluene	5.A Step A Step A 3-Benzyloxybenzyl azide To a stirred solution of 3-benzyloxybenzyl alcohol (5.0 g, 23.3 mmol) and diphenylphosphoryl azide (7.7 g, 28.0 mmol) in dry toluene (40 mL) at 0° C., was added 1,8-diazabicyclo[5.4.0]undec-7-ene (3.9 g, 25.6 mmol). The resulting mixture was allowed to warm to ambient temperature, and stirred under argon for 18 hrs, then washed with water (2*15 mL), then 5% hydrochloric acid (15 mL). The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography on silica, eluding with hexane -4% ethyl acetate to yield the product as a colorless oil.
	With diphenylphosphoranyl azide In toluene	1.H Step H Step H 3-Benzyloxybenzyl Azide To a stirred solution of 3-benzyloxybenzyl alcohol (5.0 g, 23.3 mmol) and diphenylphosphoryl azide (7.7 g, 28.0 mmol) in dry toluene (40 mL) at 0° C., was added 1,8-diazabicyclo[5.4.0]undec-7-ene (3.9 g, 25.6 mmol). The resulting mixture was allowed to warm to ambient temperature, and stirred under argon for 18 hours, then washed with water (2*15 mL), then 5% hydrochloric acid (15 mL). The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography on silica, eluding with hexane-4% EtOAc to yield the product as a colorless oil.

Reference： [1]Current Patent Assignee: MERCK & CO INC - US6410534, 2002, B1
[2]Current Patent Assignee: MERCK & CO INC - US6441017, 2002, B1

49
[ 1700-30-7 ]
[ 7143-01-3 ]
3-(Benzyloxy)benzylmethanesulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In dichloromethane	1.H Step H Step H Preparation of 3-(Benzyloxy)benzylmethanesulfonate To a solution of 3-(benzyloxy)benzyl alcohol (1.546 g, 7.21 mmol) in 20 mL of CH2Cl2 at 0° C. was added triethylamine (1.206 mL, 8.65 mmol) and methanesulfonic anhydride (1.257 g, 7.21 mmol). After 45 minutes, the solution was poured into EtOAc, washed with 10% HCl soln., sat. aq. NaHCO3 and brine, dried (Na2SO4), filtered, and concentrated in vacuo to provide the titled product as a yellow oil.

Reference： [1]Current Patent Assignee: MERCK & CO INC - US6562823, 2003, B1

50
[ 100-39-0 ]
[ 100-83-4 ]
[ 1700-30-7 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium borohydrid; potassium carbonate In methanol; acetonitrile	R.20 3-Benzyloxybenzyl alcohol Reference Example 20 3-Benzyloxybenzyl alcohol 3-Hydroxybenzaldehyde (25.0 g) and 28.3 g of potassium carbonate were added to 150 ml of acetonitrile, then 26.8 ml of benzyl bromide was added dropwise, and the mixture was stirred at 60 °C for 4 hours. Dilute hydrochloric acid was added to the reaction mixture, and the mixture was extracted with diethyl ether. The organic layer was washed successively with a saturated aqueous sodium hydrogen carbonate solution and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the resulting residue was washed with hexane and then dissolved in 150 ml of methanol. To the solution was added portionwise 3.3 g of sodium borohydride under ice-cooling, and the mixture was stirred under an argon atmosphere at room temperature for 10 minutes. The reaction mixture was acidified with dilute hydrochloric acid, and the mixture was extracted with diethyl ether. The organic layer was washed successively with a saturated aqueous sodium hydrogen carbonate solution and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give 32.0 g of 3-benzyloxybenzyl alcohol. 1H-NMR(CDCl3) δ ppm: 4.67 (2H, s), 5.08 (2H, s), 6.87-7.05 (3H, m), 7.26-7.45 (6H, m)

Reference： [1]Current Patent Assignee: KISSEI PHARMACEUTICAL COMPANY LIMITED - EP1020434, 2000, A1

51
[ 1700-30-7 ]
[ 124-63-0 ]
[ 24033-03-2 ]

Yield	Reaction Conditions	Operation in experiment
67%	Stage #1: (3-(benzyloxy)phenyl)methanol; methanesulfonyl chloride With triethylamine In dichloromethane at 0 - 20℃; Stage #2: With sodium hydrogencarbonate In dichloromethane; water	2 Preparation Example 2. 3-Benzyloxybenzylamine To a solution of 3-benzyloxybenzyl alcohol (3.0g, 14.0mmol) in dichloromethane (30mL) was added methanesulfonyl chloride (1.39mL, 16.8mmol) and triethylamine (2.34mL, 16.8mmol) on an ice bath, and the solution was stirred overnight. The reaction solution was diluted with dichloromethane, washed with aqueous solution of 5% sodium bicarbonate, and then, dried over anhydrous magnesium sulfate. The solvent was evaporated, then, the residue was purified by silica gel column chromatography (hexane : ethyl acetate = 10 : 1), and 1-benzyloxy-3-chloromethyl-benzene (2.2g, 67%) was obtained as a colorless oil. Next, to a solution of iminodicarboxylic acid di-tert-butyl ester (2.12g, 8.76mmol) in N,N-dimethylformamide (13mL) was added sodium hydride (0.39g, 9.86mmol, 60% in oil), the solution was stirred at 60°C for 6 hours, 1-benzyloxy-3-chloromethyl-benzene (1.0g, 4.30mmol) was added, and the solution was further stirred at 60°C for 4 hours. The reaction solution was allowed to room temperature, then, dichloromethane and water were added for partitioning, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated, then, the residue was purified by silica gel column chromatography (hexane : ethyl acetate = 10 : 1), and (3-benzyloxybenzyl) iminodicarboxylic acid di-tert-butyl ester (691 mg, 39%) was obtained as a pale yellow oil. Lastly, (3-benzyloxybenzyl) iminodicarboxylic acid di-tert-butyl ester (691 mg, 1.67mmol) was cooled on an ice bath, trifluoroacetic acid (3mL) was added, and the solution was stirred for 30 minutes. An aqueous solution of saturated sodium bicarbonate was added to the reaction solution, which was then extracted with ethyl acetate and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the title compound (292mg, 82%) was obtained as a white waxy solid. This was used in the next reaction without further purification.

Reference： [1]Current Patent Assignee: EISAI CO LTD - EP1782811, 2007, A1 Location in patent: Page/Page column 67

52
[ 773837-37-9 ]
[ 1700-30-7 ]
[ 20967-96-8 ]

Yield	Reaction Conditions	Operation in experiment
85%		Reference Example 84 To a mixture of (3-benzyloxyphenyl) methanol (22.09 g) and dichloroethane (250 ml) was added thionyl chloride (14.8 ml) at 0 C, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated, and the residue was poured into aqueous sodium hydrogen carbonate and extracted with diethyl ether. The diethyl ether layer was washed with saturated aqueous sodium chloride solution, dried (MgS04) and concentrated to give a residue. A mixture of the obtained residue, sodium cyanide (5.32 g) and N, N- dimethylformamide (100 ml) was stirred overnight at50 C. The reaction mixture was poured into water, and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried(MgS04) and concentrated. The residue was subjected to silica gel column chromatography, and (3-benzyloxyphenyl) acetonitrile (19.64 g, yield85%) was obtained as a pale-yellow oily substance from a fraction eluted with ethyl acetate-hexane (1: 3, volume ratio). 1H-NMR(CDC13)$ : 3.72 (2H, s), 5.07 (2H, s), 6.89-6. 96 (3H,m), 7.24-7. 45 (6H, m).

Reference： [1]Patent: WO2003/99793,2003,A1 .Location in patent: Page 158

53
[ 1700-30-7 ]
[ 999-97-3 ]
[ 1174495-96-5 ]

Yield	Reaction Conditions	Operation in experiment
85%	With saccharin sulfonic acid In acetonitrile at 20℃; for 0.333333h; chemoselective reaction;

Reference： [1]Location in patent: experimental part Shirini, Farhad; Zolfigol, Mohammad Ali; Abedini, Masoumeh [Monatshefte fur Chemie, 2009, vol. 140, # 1, p. 61 - 64]

54
[ 1700-30-7 ]
[ 124-63-0 ]
[ 191097-27-5 ]

Yield	Reaction Conditions	Operation in experiment
88%	With triethylamine In dichloromethane at 0℃; for 3h;	26.2 3-(benzyloxy)benzyl methanesulfonate 26c Compound 26b (500 mg, 2.33 mmol) was dissolved in dichloromethane (15 mL)Add triethylamine (472 mg, 4.66 mmol) and cool to 0 ° C and stir.After methanesulfonyl chloride (400 mg, 3.49 mmol) was dropped into the above reaction system,The reaction was carried out at 0 ° C for 3 hours.Stop after the reaction is over,Add 50mL of water,Dichloromethane extraction (50mLX3),The combined organic phases were dried over anhydrous sodium sulfate.Concentration gave the title compound 26c (600 mg, yield: 88%)
	With triethylamine In dichloromethane at -30℃; for 4.5h; Inert atmosphere;
	With triethylamine In 1,2-dimethoxyethane for 0.0833333h;	5.1.1. 4-(4-Benzyloxyphenylmethyl)-5-trifluoromethyl-1,2-dihydro-3H-pyrazol-3-one (9a) General procedure: MsCl (0.88 mL, 11.4 mmol), under ice cooling, was added to a solution of 4-benzyloxyphenylmethanol (2.33 g, 10.9 mmol) and Et3N (1.67 mL, 11.9 mmol) in 1,2-dimethoxyethane (DME: 10 mL), and the mixture was stirred for 5 min. The insoluble material was removed by filtration and washed with DME (2 mL). The filtrate and washing were added to the mixture prepared by the addition of NaH (478 mg, 12.0 mmol, 60% oil dispersion) into a solution of ethyl 4,4,4-trifluoroacetoacetate (2.00 g, 10.9 mmol) in DME (15 mL) under ice cooling and stirring for 5 min, then the mixture was refluxed for 11 h. After cooling to room temperature, 1 M HCl (20 mL) was added, and the resulting mixture was extracted with EtOAc. The extract was washed with brine and dried over anhydrous MgSO4. The solvent was removed under reduced pressure to give crude ethyl 2-(4-benzyloxyphenylmethyl)-4,4,4-trifluoroacetoacetate (8a). This material was dissolved in toluene (30 mL), and N2H4·H2O (1.05 mL, 21.7 mmol) was added to the solution. After refluxing for 7 h, water was added, and the mixture was extracted with EtOAc. The extract was washed with brine and dried over anhydrous MgSO4. Next, the solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: CH2Cl2/MeOH = 10:1) to give 9a (2.46 g, 65%) as a white solid.

	With triethylamine In dichloromethane at 0℃; for 1h;	57.A (57A) (57A) Tert-butyl trans-4-{3-[(2-ethoxy-2-oxoethoxy)methyl]phenoxy}cyclohexanecarboxylate To a solution of [3-(benzyloxy)phenyl]methanol (2.27 g, 10.6 mmol) in dichloromethane (100 mL), triethylamine (2.2 mL, 15.9 mmol) and methanesulfonyl chloride (0.93 mL, 11.7 mmol) were added, and the resulting mixture was stirred at 0°C for 1 hour. To the reaction solution, 1 N hydrochloric acid was added, and extraction was performed with ethyl acetate. The obtained organic layer was washed with water and a saturated aqueous solution of sodium chloride and then dried over anhydrous sodium sulfate. Then, the solvent was distilled off under reduced pressure, whereby a crude product was obtained. The obtained crude product was dissolved in N,N-dimethylformamide (70 mL), and sodium hydride (63%, 812 mg, 21.2 mmol) was added thereto at room temperature, and then, the resulting mixture was stirred at room temperature for 30 minutes. Thereafter, ethyl glycolate (1.7 g, 15.9 mmol) was added to the reaction solution, and the resulting mixture was stirred at 50°C for 2 hours. To the reaction solution, a saturated aqueous solution of ammonium chloride was added, and extraction was performed with ethyl acetate. The obtained organic layer was washed with water and a saturated aqueous solution of sodium chloride and then dried over anhydrous sodium sulfate. Then, the solvent was distilled off under reduced pressure, and the obtained residue was roughly purified by silica gel column chromatography, whereby a crude product was obtained. To a solution of the obtained crude product in methanol (30 mL), palladium on carbon (10%, 100 mg) was added, and the resulting mixture was stirred under a hydrogen atmosphere at room temperature for 1 hour. The reaction solution was filtered through a Celite filter, and the obtained mother liquor was concentrated under reduced pressure, whereby a crude product was obtained. To a solution (40 mL) of the obtained crude product in toluene, tert-butyl cis-4-hydroxycyclohexanecarboxylate (722 mg, 3.6 mmol) and cyanomethylenetributylphosphorane (1.0 g, 4.3 mmol) were added, and the resulting mixture was stirred at 100°C for 90 minutes. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate = 95:5 to 85:15 (v/v)), whereby the target compound was obtained as a colorless oil (856 mg, yield: 60%). 1H NMR(CDCl3, 400MHz): δ1.29(3H, t, J=7.2Hz), 1.45-1.60(13H, m), 2.03-2.06(2H, m), 2.16-2.20(2H, m), 2.21-2.27(1H, m), 4.09(2H, s), 4.18-4.27(3H, m), 4.60(2H, s), 6.83-6.84(1H, m), 6.91-6.93(2H, m), 7.24(1H, d, J=8.2Hz).
	With triethylamine In dichloromethane for 12h; Cooling with ice;	5.1.5. Benzyl methanesulfonate (11a) General procedure: To a solution of compound 8a (1.08 g, 10 mmol) and Et3N (1.52g, 15 mmol) in anhydrous DCM (100 mL) was added dropwisemethanesulfonyl chloride (1.36 g, 12 mmol) in anhydrous DCM(20 mL). The mixture was stirred for 12 h while being cooled withan ice-water bath. DCM was evaporated under vacuum. The residuewas dissolved in EtOAc (100 mL) and washed with 10% HCl(3 100 mL), saturated NaHCO3 (3 100 mL) and brine (3 100mL), and then dried over MgSO4 overnight. EtOAc was evaporatedto give 11a as yellow oil (1.77 g, yield: 95%). ESI-MS m/z 187.4 [M+H]+. The crude product was used directly in the next reactionwithout further purification.Compounds 11b-11w, 11aa-11ff and 23a-23h were preparedusing the same procedure described above.

Reference： [1]Current Patent Assignee: JIANGSU HENGRUI MEDICINE CO., LTD. - CN110218218, 2019, A Location in patent: Paragraph 0713; 0715; 0720-0722
[2]Location in patent: experimental part Banfi, Luca; Basso, Andrea; Giardini, Lorenzo; Riva, Renata; Rocca, Valeria; Guanti, Giuseppe [European Journal of Organic Chemistry, 2011, # 1, p. 100 - 109]
[3]Fushimi, Nobuhiko; Fujikura, Hideki; Shiohara, Hiroaki; Teranishi, Hirotaka; Shimizu, Kazuo; Yonekubo, Shigeru; Ohno, Kohsuke; Miyagi, Takashi; Itoh, Fumiaki; Shibazaki, Toshihide; Tomae, Masaki; Ishikawa-Takemura, Yukiko; Nakabayashi, Takeshi; Kamada, Noboru; Ozawa, Tomonaga; Isaji, Masayuki; Kobayashi, Susumu [Bioorganic and medicinal chemistry, 2012, vol. 20, # 22, p. 6598 - 6612,15]
[4]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP2623492, 2013, A1 Location in patent: Paragraph 0458-0465
[5]Cao, Jiangying; Ma, Chunhua; Zang, Jie; Gao, Shuai; Gao, Qianwen; Kong, Xiujie; Yan, Yugang; Liang, Xuewu; Ding, Qin'ge; Zhao, Chunlong; Wang, Binghe; Xu, Wenfang; Zhang, Yingjie [Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 12, p. 3145 - 3157]

55
[ 1700-30-7 ]
[ 96995-06-1 ]

Yield	Reaction Conditions	Operation in experiment
89%	With iodine; triphenylphosphine In acetonitrile at 20℃; for 3h; Inert atmosphere;
89%	With iodine; triphenylphosphine In acetonitrile at 20℃; for 3h; Inert atmosphere; Darkness;

Reference： [1]Mai, Thi Thoa; Branca, Mathieu; Gori, Didier; Guillot, Régis; Kouklovsky, Cyrille; Alezra, Valérie [Angewandte Chemie - International Edition, 2012, vol. 51, # 20, p. 4981 - 4984]
[2]Mai, Thi Thoa; Viswambharan, Baby; Gori, Didier; Guillot, Régis; Naubron, Jean-Valère; Kouklovsky, Cyrille; Alezra, Valérie [Chemistry - A European Journal, 2017, vol. 23, # 24, p. 5787 - 5798]

56
[ 1700-30-7 ]
[ 123-08-0 ]
[ 1266666-42-5 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: (3-(benzyloxy)phenyl)methanol With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0℃; for 0.25h; Stage #2: 4-hydroxy-benzaldehyde In tetrahydrofuran at 0 - 20℃;	To a stirring solution of triphenylphosphine (1.1 mmols) in THF (2 mLs) was added 34 (1.1 mmols). The solution was immediately cooled to 0° C. and diisopropyl azodicarboxylate (1.1 mmols) was added dropwise and the mixture was stirred at this low temperature for 15 minutes. After this time, 4-hydroxybenzaldehyde (1 mmol) was added to the reaction vessel, still stirring at 0° C. The mixture was warmed slowly to ambient temperature and stirred for 15 hours. At this time, the THF was evaporated, reconstituted in Et2O and filtered through a small portion of silica gel. The eluent was collected and evaporated to dryness. The title product (0.45 mmols) was recovered after flash chromatography. 1H NMR (300 MHz, CDCl3) δ 9.89 (s, 1H), 7.91-7.77 (m, 2H), 7.50-7.30 (m, 6H), 7.03 (ddd, J=5.1, 11.5, 24.0, 5H), 5.13 (s, 2H), 5.08 (s, 2H). 13C NMR (75 MHz, CDCl3) δ 191.04, 163.88, 159.36, 137.82, 136.98, 132.24, 130.09, 128.86, 128.29, 127.74, 120.05, 115.39, 114.79, 114.14, 77.70, 77.27, 76.85, 70.25.

Reference： [1]Current Patent Assignee: UNIVERSITY OF VIRGINIA - US2012/214858, 2012, A1 Location in patent: Page/Page column 29

57
[ 1700-30-7 ]
[ 834-17-3 ]

Yield	Reaction Conditions	Operation in experiment
75%	With chlorocarbonylbis(triphenylphosphine)iridium(I); hydrazine hydrate; potassium hydroxide In methanol at 160℃; for 3h; Sealed tube;
75%	With chlorocarbonylbis(triphenylphosphine)iridium(I); hydrazine hydrate; potassium hydroxide In methanol at 160℃; for 3h; Sealed tube;

Reference： [1]Huang, Jian-Lin; Dai, Xi-Jie; Li, Chao-Jun [European Journal of Organic Chemistry, 2013, # 29, p. 6496 - 6500]
[2]Dai, Xi-Jie; Li, Chao-Jun [Journal of the American Chemical Society, 2016, vol. 138, # 16, p. 5433 - 5440]

58
[ 1476847-56-9 ]
[ 1700-30-7 ]
6-(4-((3-(benzyloxy)benzyl)oxy)-6-methoxybenzofuran-2-yl)-2-methoxyimidazo[2,1-b][1,3,4]thiadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 22℃; for 3h; Inert atmosphere; Sonication;	205 6-(4-((3-(Benzyloxy)benzyl)oxy)-6-methoxybenzofuran-2-yl)-2-methoxyimidazo[2,1-b][1,3,4]thiadiazole A mixture of 6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)benzofuran-4-ol (Example 204, 0.100 g, 0.315 mmol), triphenylphosphine (0.100 g, 0.378 mmol) and 3-benzyloxybenzyl alcohol (0.081 g, 0.378 mmol) in a 50 ml flask was maintained under vacuum for 10 min and then purged with nitrogen. Dry tetrahydrofuran (10 ml) was added and the resulting mixture was slightly warmed and maintained in an ultrasonic bath for 5 min. The cooled mixture (still heterogeneous) was treated at 22 °C with a solution of diisopropyl azodicarboxylate (0.076 g, 0.378 mmol) in tetrahydrofuran (2 ml) added dropwise over 2 min. The mixture was then stirred at 22 °C for 3 h (the mixture was placed in the ultrasonic bath for 5 min every 10 min for the first 40 min of the reaction; the solution should be clear and homogeneous at this point). The reaction mixture was quenched by the addition of dichloromethane (100 ml) and saturated sodium bicarbonate (10 ml). The organic phase was washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. Chromatography of the residue on silica gel (2.5 x 12 cm, elution toluene - ethyl acetate 5%) gave 0.1 13 g (70% yield) of the title material as a white solid (> 95% pure by hplc). Recrystallization of this material from ethyl acetate (3 ml) gave 0.082 g of pure title material as colorless prisms. LC (Method A): 2.482 min. HRMS(ESI) calcd for C28H24N3O5S [M+H]+ m/z 514.1431 , found 514.1406. NMR (CDCl3, 600 Mz) δ 3.81 (s, 3H), 4.18 (s, 3H), 5.06 (s, 2H), 5.14 (s, 2H), 6.36 (d, J = 2.82 Hz, 1H), 6.67 (broad d, 1H), 6.91 (dd, J = 8.16, 2.13 Hz, 1H), 7.04 (d, J = 7.57 Hz, 1H), 7.06 (s, 1H), 7.09 (broad s, 1H), 7.26 - 7.43 (m, 6 H), 7.82 (s, 1H).
70%	With trisubstituted phosphine; 1,1'-(azodicarbonyl) derivative In tetrahydrofuran at 23℃; for 3h; Inert atmosphere; Sonication;

Reference： [1]Current Patent Assignee: UNIVERSITY OF MONTREAL; BRISTOL-MYERS SQUIBB CO - WO2013/163244, 2013, A1 Location in patent: Paragraph 00233
[2]Miller, Michael M.; Banville, Jacques; Friends, Todd J.; Gagnon, Mark; Hangeland, Jon J.; Lavallée, Jean-François; Martel, Alain; O'Grady, Harold; Rémillard, Roger; Ruediger, Edward; Tremblay, François; Posy, Shana L.; Allegretto, Nick J.; Guarino, Victor R.; Harden, David G.; Harper, Timothy W.; Hartl, Karen; Josephs, Jonathan; Malmstrom, Sarah; Watson, Carol; Yang, Yanou; Zhang, Ge; Wong, Pancras; Yang, Jing; Bouvier, Michel; Seiffert, Dietmar A.; Wexler, Ruth R.; Lawrence, R. Michael; Priestley, E. Scott; Marinier, Anne [Journal of Medicinal Chemistry, 2019, vol. 62, # 16, p. 7400 - 7416]

59
[ 3137-63-1 ]
[ 1700-30-7 ]
4-(3-(benzyloxy)benzyloxy)-2-(trichloromethyl)quinazoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With dmap In toluene at 130℃; for 1h; Microwave irradiation; Sealed tube;	21 4.1.3. General procedure for the preparation of compounds 2 to 34 General procedure: A mixture of 4-chloro-2-trichloromethylquinazoline 1 (0.2 g, 0.71 mmol), DMAP (26 mg, 0.21 mmol, 0.3 equiv) and adequate alcohol derivative (0.85 mmol, 1.2 equiv) in toluene (3 mL) was introduced in miniaturized sealed reactor (5mL). The reaction mixture was irradiated in a monomode microwave oven, for 1 h at 130°C. After removal of the toluene under reduced pressure, the residue was purified by silica gel column chromatography and recrystallized from appropriate solvent. 4.1.21 4-(3-(Benzyloxy)benzyloxy)-2-(trichloromethyl)quinazoline (19) Yield 68%. Yellow powder. Mp 96 °C, (isopropanol). 1H NMR (200 MHz, CDCl3) δ = 8.23 (dd, J = 1 Hz; 8 Hz, 1H), 8.10 (d, J = 8 Hz, 1H), 7.91 (td, J = 1 Hz; 8 Hz, 1H), 7.69-7.61 (m, 1H), 7.47-7.18 (m, 8H), 5.72 (s, 1H), 5.72 (s, 2H), 5.10 (s, 2H). 13C NMR (50 MHz, CDCl3) δ = 167.6, 160.1, 159.0, 150.4, 137.2, 136.9, 134.5, 130.0, 129.7, 128.9, 128.8, 128.6, 128.0, 127.5, 123.7, 121.4, 115.5, 115.3, 115.0, 97.2, 70.1, 69.3. LC-MS (ESI+) tR 5.87 min, m/z [M + H]+ 458.74/460.72/462.84. MW: 459.75 g/mol. Anal. Calcd for C23H17Cl3N2O2: C, 60.09; H, 3.73; N, 6.09. Found: C, 59.87; H, 3.70; N, 5.98.

Reference： [1]Gellis, Armand; Primas, Nicolas; Hutter, Sébastien; Lanzada, Gilles; Remusat, Vincent; Verhaeghe, Pierre; Vanelle, Patrice; Azas, Nadine [European Journal of Medicinal Chemistry, 2016, vol. 119, p. 34 - 44]

60
[ 38359-74-9 ]
[ 1700-30-7 ]
7-(3-(benzyloxy)benzyloxy)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride In 1-methyl-pyrrolidin-2-one; mineral oil at 100 - 130℃;	2 General Route 1 General procedure: General Route 1 : I [00103] NaH (2.0-4.0 eq, 60% dispersion in oil) was added to a mixture of ROH (1.5- 4.0 eq), 7-bromo-3H-[l,2,3]triazolo[4,5-b]pyridin-5-amine or 7-chloro-3H- [l,2,3]triazolo[4,5-b]pyridin-5-amine (1.0 eq) in NMP (0.10-0.50 M) and stirred at 100- 130 °C for 1-3 days. The reaction was quenched with aqueous ammonium acetate, partially concentrated and purified by prep HPLC to yield the desired product.Example 2 was synthesized from (3-(benzyloxy)phenyl)methanol and Intermediate 2 using General Route 1. MS(ESI) m/z 348.3 (M+H). lH NMR (500 MHz, CD3OD) δ 7.43 - 7.38 (m, 2H), 7.38 - 7.30 (m, 3H), 7.29 - 7.23 (m, 1H), 7.16 - 7.12 (m, 1H), 7.10 (d, J=7.4 Hz, 1H), 7.03 (dd, J=8.0, 2.2 Hz, 1H), 6.30 (s, 1H), 5.45 (s, 2H), 5.12 (s, 2H). Analytical HPLC Method A: 6.47 min, 94%; Method B: 7.14 min, 97%.

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2017/40450, 2017, A1 Location in patent: Paragraph 00103; 00131

61
[ 1700-30-7 ]
[ 20349-89-7 ]
C₂₄H₂₄O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With triphenylphosphine; diethylazodicarboxylate In toluene at 70℃; for 3h; Inert atmosphere;

Reference： [1]Sayama, Misa; Inoue, Asuka; Nakamura, Sho; Jung, Sejin; Ikubo, Masaya; Otani, Yuko; Uwamizu, Akiharu; Kishi, Takayuki; Makide, Kumiko; Aoki, Junken; Hirokawa, Takatsugu; Ohwada, Tomohiko [Journal of Medicinal Chemistry, 2017, vol. 60, # 14, p. 6384 - 6399]

62
[ 1700-30-7 ]
C₁₈H₁₃NO₃ [ No CAS ]
C₂₅H₂₁NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	Stage #1: (3-(benzyloxy)phenyl)methanol; C₁₈H₁₃NO₃ With trifluoroacetic acid In 1,2-dichloro-ethane at 80℃; for 16h; Stage #2: With potassium carbonate In methanol; 1,2-dichloro-ethane at 23℃; for 24h;
94%	Stage #1: (3-(benzyloxy)phenyl)methanol; C₁₈H₁₃NO₃ With trifluoroacetic acid In 1,2-dichloro-ethane at 80℃; for 16h; Stage #2: With potassium carbonate In methanol; 1,2-dichloro-ethane at 23℃; for 24h;	4 Acetal 1b: A 2-dram vial with a PTFE-lined cap was charged with (3-(benzyloxy)phenyl)methanol (8b, 65.3 mg, 0.305 mmol) and benzoate S1 (113 mg, 0.388 mmol). These were dissolved in DCE (1.00 mL), and TFA (2.2 μL, 0.0297 mmol) was added. The resulting mixture was heated to 80° C. and stirred for 16 h. After cooling to room temperature, K2CO3 (82.8 mg, 0.600 mmol) and MeOH (1.00 mL) were added, and the resulting mixture was stirred at 23° C. for 24 h. The mixture was then filtered through a short pad of silica gel, eluting with EtOAc (30 mL), and the filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography (4:1 hexanes/EtOAc eluent) to afford acetal 1b (110 mg, 94% yield, Rf=0.16 in 5:1 hexanes/EtOAc) as a colorless oil. 1H NMR: (400 MHz, CDCl3) δ 8.18 (d, J=8.5 Hz, 1H), 8.05 (s, 1H), 7.85 (d, J=8.1 Hz, 1H), 7.77-7.69 (m, 1H), 7.61-7.54 (m, 1H), 7.43 (d, J=7.3 Hz, 2H), 7.37 (t, J=7.3 Hz, 2H), 7.34-7.28 (m, 1H), 7.26 (t, J=7.9 Hz, 2H), 7.12 (s, 1H), 7.04 (d, J=7.6 Hz, 1H), 6.89 (dd, J=8.2, 2.4 Hz, 1H), 6.31 (s, 1H), 5.39 (d, J=13.3 Hz, 1H), 5.23 (d, J=13.3 Hz, 1H), 5.07 (s, 2H), 4.93 (d, J=11.6 Hz, 1H), 4.86 (d, J=11.6 Hz, 1H). 13C NMR: (100 MHz, CDCl3) δ 159.6, 159.1, 148.7, 139.4, 137.3, 130.8, 130.0, 129.7, 129.6, 129.1, 128.8, 128.10, 128.06, 127.8, 127.3, 120.9, 114.6, 114.5, 103.6, 70.4, 70.13, 70.12. IR: (film) 1585, 1503, 1265, 1073, 1022 cm-1. HRMS: (ESI+) m/z calc'd for (M+H)+[C25H21NO3+H]+: 384.1594, found 384.1599.

Reference： [1]Li, Qiankun; Ferreira, Eric M. [Chemistry - A European Journal, 2017, vol. 23, # 48, p. 11519 - 11523]
[2]Current Patent Assignee: UNIVERSITY SYSTEM OF GEORGIA - US2018/65909, 2018, A1 Location in patent: Paragraph 0139-0144

63
[ 69026-14-8 ]
[ 1700-30-7 ]

Yield	Reaction Conditions	Operation in experiment
	With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; for 12h; Inert atmosphere;	3.2. (3-(Benzyloxy)phenyl)methanol (17) LiAlH4 (2.5 g, 65.7 mmol) was taken in dry THF (40 mL) under nitrogen atmosphere and cooled to 0. Compound 16 (10 g, 43.8 mmol) dissolved in dry THF (70 mL) was added drop wise to the above solution. It was allowed to stir at room temperature for 12 h. Upon completion, the mixture was cooled to 0 and was quenched by the dropwise addition with H2O (2.5 mL), 15% aqueous NaOH (2.5 mL), H2O (2.5 mL × 3). The mixture was warmed to room temperature, stirred for 15 min and diluted with DCM. MgSO4 was added and the mixture was stirred a further 15 min. the solid was filtered, the filtrate was concentrated under reduced pressure, compound 17 was obtained quantitatively and used without further purification.

Reference： [1]Bi, Fangchao; Ji, Shengli; Venter, Henrietta; Liu, Jingru; Semple, Susan J.; Ma, Shutao [Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 5, p. 884 - 891]

64
[ 620-24-6 ]
[ 1700-30-7 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate In N,N-dimethyl-formamide at 80℃;	(3-Ethoxyphenyl)methanol (13c). General procedure: To a solution of compound 12 (200 mg, 1.61 mmol, 1.0 eq) dissolved in DMF were added K2CO3 (668 mg, 4.83 mmol, 3.0 eq), bromoethane (193 mg, 1.77 mmol, 1.1 eq) (for most other intermediates, R4Br or R4I could be 1.1 eq or 1.5 eq).The mixture was stirred at 60 °C overnight. For most other intermediates, the stirring could be 80 °C for 0.5-1.0 h. Then the mixturewas cooled, poured into water and extracted with EtOAc. The organiclayer was washed with saturated brine, dried over NaSO4 and concentrated under reduced pressure to give the crude (3-ethoxyphenyl)methanol (13c) as a colorless or light yellow liquid (210 mg, 86%yield). For most other intermediates, the crude product was further purified by silica gel chromatography with petroleum ether/EtOAc (1/5-1/2) to obtain products which were monitored by TLC. The intermediates 13c-13j, 13o-13u, 13w-13x were not characterized but were used directly in the next steps.

Reference： [1]Hu, Qingqing; Wang, Chao; Xiang, Qiuping; Wang, Rui; Zhang, Cheng; Zhang, Maofeng; Xue, Xiaoqian; Luo, Guolong; Liu, Xiaomin; Wu, Xishan; Zhang, Yan; Wu, Donghai; Xu, Yong [Bioorganic Chemistry, 2020, vol. 94]

65
[ 1700-30-7 ]
[ 614-16-4 ]
3-(benzyloxy)benzyl benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	With potassium <i>tert</i>-butylate In neat (no solvent) at 140℃; for 12h; Schlenk technique; Inert atmosphere; Sealed tube;

Reference： [1]Subaramanian, Murugan; Ramar, Palmurukan M.; Rana, Jagannath; Gupta, Virendra Kumar; Balaraman, Ekambaram [Chemical Communications, 2020, vol. 56, # 58, p. 8143 - 8146]

66
[ 1700-30-7 ]
[ 62-53-3 ]
[ 39860-74-7 ]

Yield	Reaction Conditions	Operation in experiment
79%	With potassium <i>tert</i>-butylate In octane at 140℃; for 24h; Inert atmosphere; Sealed tube;

Reference： [1]Subaramanian, Murugan; Ramar, Palmurukan M.; Sivakumar, Ganesan; Kadam, Ravishankar G.; Petr, Martin; Zboril, Radek; Gawande, Manoj B.; Balaraman, Ekambaram [ChemCatChem, 2021, vol. 13, # 20, p. 4334 - 4341]

67
[ 7781-98-8 ]
[ 1700-30-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 16 h / 80 °C / Inert atmosphere; Schlenk technique 2: sodium t-butanolate; 15-crown-5; hydrogen; (1-(2-(2,3-diisopropyl-1-methylguanidino)ethyl)-3-mesityl-1,3-dihydro-2H-imidazol-2-ylidene)copper(I) chloride / 1,4-dioxane / 24 h / 60 °C / Inert atmosphere

Reference： [1]Kaicharla, Trinadh; Ngoc, Trung Tran; Teichert, Johannes F.; Tzaras, Dimitrios-Ioannis; Zimmermann, Birte M. [Journal of the American Chemical Society, 2021, vol. 143, # 40, p. 16865 - 16873]

68
[ 63888-94-8 ]
[ 1700-30-7 ]

Yield	Reaction Conditions	Operation in experiment
75%	With 15-crown-5; (1-(2-(2,3-diisopropyl-1-methylguanidino)ethyl)-3-mesityl-1,3-dihydro-2H-imidazol-2-ylidene)copper(I) chloride; hydrogen; sodium t-butanolate In 1,4-dioxane at 60℃; for 24h; Inert atmosphere;

Reference： [1]Kaicharla, Trinadh; Ngoc, Trung Tran; Teichert, Johannes F.; Tzaras, Dimitrios-Ioannis; Zimmermann, Birte M. [Journal of the American Chemical Society, 2021, vol. 143, # 40, p. 16865 - 16873]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	1700-30-7	MDL No. :	MFCD00004642
Formula :	C₁₄H₁₄O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	AFKLSWIRJUJWKY-UHFFFAOYSA-N
M.W :	214.26	Pubchem ID :	74341
Synonyms :

Num. heavy atoms :	16
Num. arom. heavy atoms :	12
Fraction Csp3 :	0.14
Num. rotatable bonds :	4
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	63.55
TPSA :	29.46 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.55 cm/s

Log Po/w (iLOGP) :	2.41
Log Po/w (XLOGP3) :	2.9
Log Po/w (WLOGP) :	2.45
Log Po/w (MLOGP) :	2.68
Log Po/w (SILICOS-IT) :	3.27
Consensus Log Po/w :	2.74

[ CAS No. 1700-30-7 ]

Quality Control of [ 1700-30-7 ]

Related Doc. of [ 1700-30-7 ]

Product Details of [ 1700-30-7 ]

Calculated chemistry of [ 1700-30-7 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 1700-30-7 ]

Application In Synthesis of [ 1700-30-7 ]

[ 1700-30-7 ] Synthesis Path-Upstream 1~3

[ 1700-30-7 ] Synthesis Path-Downstream 1~68

Related Functional Groups of
[ 1700-30-7 ]

Aryls

Ethers

Alcohols

Precautionary Statements-General

Prevention

Response

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Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

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

Log S (ESOL) :	-3.29
Solubility :	0.111 mg/ml ; 0.000517 mol/l
Class :	Soluble
Log S (Ali) :	-3.18
Solubility :	0.142 mg/ml ; 0.000662 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.9
Solubility :	0.00272 mg/ml ; 0.0000127 mol/l
Class :	Moderately soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.81

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

Yield	Reaction Conditions	Operation in experiment
97%	With phosphorus tribromide In diethyl ether	Synthesis of Compound 172 Preparation of (3-benzyloxy)benzyl bromide: To a solution of (3-benzyloxy)benzyl alcohol (3.0 g, 14.0 mmol) in anhydrous diethyl ether (50 mL) was added PBr₃ (0.66 mL, 7.0 mmol) in one portion, and the resulting mixture was stirred at room temperature for 3 hours. The mixture was diluted with diethyl ether (60 mL) and washed with H₂O (240 mL), saturated NaHCO₃ (240 mL), and brine (2*40 mL). The ether layer was dried over anhydrous MgSO₄, and the solvent was removed under reduced pressure to afford (3-benzyloxy)benzyl bromide (3.76 g, 97percent) as a pale yellow solid.
97%	With phosphorus tribromide In diethyl ether	Synthesis of Compound 172 Preparation of (3-benzyloxy)benzyl bromide: To a solution of (3-benzyloxy)benzyl alcohol (3.0 g, 14.0 mmol) in anhydrous diethyl ether (50 mL) was added PBr₃ (0.66 mL, 7.0 mmol) in one portion, and the resulting mixture was stirred at room temperature for 3 hours. The mixture was diluted with diethyl ether (60 mL) and washed with H₂O (240 mL), saturated NaHCO₃ (240 mL), and brine (2*40 mL). The ether layer was dried over anhydrous MgSO₄, and the solvent was removed under reduced pressure to afford (3-benzyloxy)benzyl bromide (3.76 g, 97percent) as a pale yellow solid.
89%	With phosphorus tribromide In dichloromethane at 0 - 20℃; for 3 h;	Using the procedure reported by K. Thakkar et al., J. Med. Chem., 1993, 36 (20), 2950. [0500] Phosphorus tribromide (1.96 mL, 20.6 mmol) was added to a solution of 3-benzyloxybenzyl alcohol (4.29 g, 20 mmol) in anhydrous dichloromethane (90 mL) at 0° C. The mixture was stirred at 0° C. for 2 h and then at room temperature for 1 h. The reaction was poured onto ice/water (400 mL) and allowed to warm to room temperature. The aqueous solution was extracted with Et2O (5.x.100 mL) and the combined ethereal solution dried (MgSO4). Concentration in vacuo gave a light yellow oil which crystallised on standing to give OBS01018 as colourless needles (4.93 g, 89percent). TLC [SiO2, EtOAc-n-hexane (1:1)] Rf=0.9; m.p. 55-56° C. [Lit. (Petroleum ether): 55° C.]; 1H-NMR (400 MHz, CDCl3) 4.44 (2H, s), 5.05 (2H, s); 6.78 (1H, d, J=2), 6.93 (1H, m), 7.22 (1H, t, J=8), 7.40 (5H, m).

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