Name: 24324-17-2|9-Fluorenemethanol|98%
Brand: Ambeed
SKU: A221246
Price: 6.0 USD
Availability: InStock
Rating: 97 (26 reviews)

1
[ 24324-17-2 ]
[ 98-59-9 ]
[ 71532-40-6 ]

Yield	Reaction Conditions	Operation in experiment
83%	With pyridine In chloroform at 0℃; for 2h;
78%	In pyridine; chloroform at 20℃; for 6h;
71%	With pyridine In chloroform at 20℃; for 2h;

55%	With pyridine In chloroform at 0 - 22℃;
	With pyridine at 0℃; for 2h;

Reference： [1]Albericio, F.; Nicolas, E.; Rizo, J.; Ruiz-Gayo, M.; Pedroso, E.; Giralt, E. [Synthesis, 1990, # 2, p. 119 - 122]
[2]Gu, Xuyuan; Ying, Jinfa; Agnes, Richard S.; Navratilova, Edita; Davis, Peg; Stahl, Gannon; Porreca, Frank; Yamamura, Henry I.; Hruby, Victor J. [Organic Letters, 2004, vol. 6, # 19, p. 3285 - 3288]
[3]Vlahov, Iontcho R.; Santhapuram, Hari Krishna R.; Wang, Yu; Kleindl, Paul J.; You, Fei; Howard, Stephen J.; Westrick, Elaine; Reddy, Joseph A.; Leamon, Christopher P. [Journal of Organic Chemistry, 2007, vol. 72, # 16, p. 5968 - 5972]
[4]Anderson, Zoe J.; Hobson, Christian; Needley, Rebecca; Song, Lijiang; Perryman, Michael S.; Kerby, Paul; Fox, David J. [Organic and Biomolecular Chemistry, 2017, vol. 15, # 44, p. 9372 - 9378]
[5]Anet; Bavin [Canadian Journal of Chemistry, 1956, vol. 34, p. 991,1002]
[6]Palate, Kleopas Y.; Epton, Ryan G.; Whitwood, Adrian C.; Lynam, Jason M.; Unsworth, William P. [Organic and Biomolecular Chemistry, 2021, vol. 19, # 6, p. 1404 - 1411]

2
[ 75-44-5 ]
[ 24324-17-2 ]
[ 28920-43-6 ]

Yield	Reaction Conditions	Operation in experiment
74%	In dichloromethane
	In dichloromethane
	With pyridine In diethyl ether 1.) 1 h, 0 deg C, 2.) 8 h, 25 deg C;

With pyridine In tetrahydrofuran at 0 - 6℃; for 13.5h; Large scale;

1.1 Preparation of Fmoc-cl 2000L glass-lined reactor in the introduction of tetrahydrofuran 900Kg,(0.38 mol) of 9-fluorenylmethanol,Pyridine 1. 5 Kg,Cool to 0-2 ° C with stirring.80 Kg solid phosgene (0.27 Kmol) was added in portions,Each 8Kg,10 times cast finished,Each vote of solid phosgene with lhr,After 10hr, the solid phosgene was added,And then at 5 ~ 6 ° C reaction 2. 5hr

Reference： [1]Vanfleteren, L.; Anteunis, M. J. O. [Bulletin des Societes Chimiques Belges, 1988, vol. 97, # 7, p. 505 - 518]
[2]Carpino,L.A.; Han,G.Y. [Journal of Organic Chemistry, 1972, vol. 37, # 22, p. 3404 - 3409]
[3]Hoffmann, H.M.R.; Iranshahi, Lotfollah [Journal of Organic Chemistry, 1984, vol. 49, # 7, p. 1174 - 1176]
[4]Current Patent Assignee: GENCHEM CHANGZHOU - CN104030962, 2016, B Location in patent: Paragraph 0036-0037

3
[ 590-92-1 ]
[ 24324-17-2 ]
[ 123963-71-3 ]

Reference： [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 661 - 667
[2]Journal of the American Chemical Society,2019,vol. 141,p. 17117 - 17124

4
[ 50-00-0 ]
[ 86-73-7 ]
[ 4425-93-8 ]
[ 24324-17-2 ]

Reference： [1]Synthesis,1992,p. 819 - 820

5
[ 86-73-7 ]
[ 20615-64-9 ]
[ 24324-17-2 ]

Reference： [1]Bulletin des Societes Chimiques Belges,1988,vol. 97,p. 505 - 518

6
[ 1989-33-9 ]
[ 24324-17-2 ]

Yield	Reaction Conditions	Operation in experiment
51%	With indium(III) bromide; 1,1,3,3-Tetramethyldisiloxane In chloroform at 60℃; for 1h; Inert atmosphere;
	With lithium aluminium tetrahydride
	With lithium aluminium tetrahydride In diethyl ether Heating;

Reference： [1]Location in patent: experimental part Sakai, Norio; Kawana, Keita; Ikeda, Reiko; Nakaike, Yumi; Konakahara, Takeo [European Journal of Organic Chemistry, 2011, # 17, p. 3178 - 3183]
[2]Krogh, Erik; Wan, Peter [Tetrahedron Letters, 1986, vol. 27, # 7, p. 823 - 826]
[3]Arlt, Michael; Boettcher, Henning; Riethmueller, Angelika; Schneider, Guenter; Bartoszyk, Gerd D.; Greiner, Hartmut; Seyfried, Christoph A. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 15, p. 2033 - 2038]

7
[ 24324-17-2 ]
[ 917-61-3 ]
[ 84418-43-9 ]

Reference： [1]Journal of Organic Chemistry,1983,vol. 48,p. 661 - 665

8
[ 24324-17-2 ]
[ 73283-56-4 ]

Yield	Reaction Conditions	Operation in experiment
90%	With 2,6-dimethylpyridine; methyltriphenoxyphosphonium iodide In N,N-dimethyl-formamide at 20℃; for 3h;
7.9%	With hydrogen iodide at 90℃; for 26h;
	With hydrogen iodide; zinc(II) iodide In chloroform

	Multi-step reaction with 2 steps 1: pyridine / diethyl ether / 1.) 1 h, 0 deg C, 2.) 8 h, 25 deg C 2: NaI / acetonitrile / 2 h / Heating
	Multi-step reaction with 2 steps 1: pyridine / diethyl ether / 1.) 1 h, 0 deg C, 2.) 8 h, 25 deg C 2: NaI / acetonitrile / 2 h / Ambient temperature

Reference： [1]Liu, Hongyan; Hashmi, Syed N.; Shaw, Barbara Ramsay [Nucleosides, nucleotides and nucleic acids, 2007, vol. 26, # 10-12, p. 1455 - 1457]
[2]Nakano, Tamaki; Okamoto, Yoshio; Hatada, Koichi [Journal of the American Chemical Society, 1992, vol. 114, # 4, p. 1318 - 1329]
[3]Meng, Qingshui; Thibblin, Alf [Journal of the American Chemical Society, 1997, vol. 119, # 21, p. 4834 - 4840]
[4]Hoffmann, H.M.R.; Iranshahi, Lotfollah [Journal of Organic Chemistry, 1984, vol. 49, # 7, p. 1174 - 1176]
[5]Hoffmann, H.M.R.; Iranshahi, Lotfollah [Journal of Organic Chemistry, 1984, vol. 49, # 7, p. 1174 - 1176]

9
[ 50-00-0 ]
[ 86-73-7 ]
[ 24324-17-2 ]

Yield	Reaction Conditions	Operation in experiment
71%	Stage #1: 9H-fluorene With n-butyllithium In tetrahydrofuran; hexane at 0℃; Stage #2: formaldehyd In tetrahydrofuran; hexane at 0 - 20℃; for 5h;	1.A (A) 60 g (0.36 mol) of fluorine was dissolved in 1,500 mL of dehydrated THF. Thereafter, 225 mL of a butyllithium hexane solution (1.6 M) was slowly added dropwise thereto at 0° C. in an argon gas atmosphere. 12 g of p-formaldehyde was then added, followed by stirring at room temperature for 5 hours. After stirring, 600 mL of a saturated sodium bicarbonate water was added, the mixture was extracted with diethyl ether, and the organic layer was washed twice with saturated saline. After drying over anhydrous magnesium sulfate, the solvent was distilled off. The resulting solid in a paste form was recrystallized from a mixed solvent of hexane and ethanol to obtain 50 g of fluorenylmethanol in a white acicular crystal form. It was confirmed that the resulting compound had the aforementioned structure represented by the formula (5) by measuring with 1H-NMR. The melting point and the measurement result of 1H-NMR are shown below. Yield: 71% Melting point: 98-101° C. 1H-NMR (270 MHz, CDCl3) δ (ppm): 1.71 (1H, s, OH), 3.6-4.3 (3H, m, CH, CH2), 7.2-7.5 (4H, m, ArH), 7.54 (2H, d, J=7.3 Hz, ArH), 7.73 (2H, d, J=7.3 Hz, ArH)
30.5%	Stage #1: 9H-fluorene With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 0.133333h; Stage #2: formaldehyd In tetrahydrofuran; hexane at 0 - 20℃; for 1.5h;
17%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In dimethyl sulfoxide at 20℃; for 0.333333h;	1.1; 2-4 step (1) Fluorene (39g, 235mmol) was dissolved in DMSO (400mL), paraformaldehyde (7g, 235mmol) was added at room temperature, and then DBU (7.1g, 47mmol) was added dropwise in 5 minutes. The reaction mixture continued to be stirred at room temperature for 15 min. The reaction was stopped by adding water (500 mL). Then it was extracted with ethyl acetate (500 mL×3), and the combined ethyl acetate phase was washed with water (200 mL×3). The collected organic phase was dried with anhydrous sodium sulfate, filtered, and the filtrate was spin-dried through the column. The eluent is petroleum ether: ethyl acetate (20:1, v/v) to obtain 9-hydroxymethyl fluorene (7.7 g, 39.3 mmol, yield 17%).

With N-benzyl-trimethylammonium hydroxide In pyridine

Reference： [1]Current Patent Assignee: SEKISUI CHEMICAL CO., LTD. - US2008/200580, 2008, A1 Location in patent: Page/Page column 7
[2]Erb, William; Levanen, Gael; Roisnel, Thierry; Dorcet, Vincent [New Journal of Chemistry, 2018, vol. 42, # 5, p. 3808 - 3818]
[3]Current Patent Assignee: TIANJIN JENKEM TECH - CN111995513, 2020, A Location in patent: Paragraph 0039-0045; 0062-0063; 0068-0069; 0074-0075
[4]Ghera,E.; Sprinzak,Y. [Journal of the American Chemical Society, 1960, vol. 82, p. 4945 - 4952]

10
[ 4025-77-8 ]
[ 24324-17-2 ]
[ 197384-32-0 ]

Yield	Reaction Conditions	Operation in experiment
74%	In dichloromethane 1.) -20 deg C to room temperature, 3 h, 2.) room temperature, 2 h;
72%	In dichloromethane at -23 - 20℃; for 7.01667h;	5 A solution of 9-(fluorenyl)methyl alcohol (4.8 g, 0.0245 mol) in dichloromethane (65 mL) is added slowly over 11 minutes to a solution of chlorosulfonylacetyl chloride (2.6 mL, 0.0245 mol) in dichloromethane (24 mL) at -23° C. to -19° C. The reaction is stirred in an ice bath for 6.5 hours, then stirred at ambient temperature for 20 minutes, and concentrated. The residue is dissolved in diethyl ether (13 mL) and slowly diluted with hexanes (26 mL). The mixture is stirred for 30 minutes and the solid which forms is collected by filtration to afford 5.96 g (72% yield) of the desired compound. 1H NMR (CDCl3) δ 7.81 (d, J=7.5 Hz, 2H), 7.65 (d, J=7.5 Hz, 2H), 7.47 (m, 2H), 7.37 (m, 2H), 4.67 (d, J=6.6 Hz, 2H), 4.64 (s, 2H), 4.31 (t, J=12.9 Hz, 1H).

Reference： [1]Gordeev, Mikhail F.; Gordon, Eric M.; Patel, Dinesh V. [Journal of Organic Chemistry, 1997, vol. 62, # 23, p. 8177 - 8181]
[2]Current Patent Assignee: PFIZER INC - US2007/299120, 2007, A1 Location in patent: Page/Page column 23

11
[ 24324-17-2 ]
[ 81196-09-0 ]
[ 223546-50-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry,1999,vol. 7,p. 161 - 175

12
[ 24324-17-2 ]
[ 73821-95-1 ]
[ 222639-66-9 ]

Reference： [1]Journal of Organic Chemistry,1999,vol. 64,p. 1972 - 1978

13
[ 20615-64-9 ]
[ 555-31-7 ]
[ 67-63-0 ]
etheric solution [ No CAS ]
[ 24324-17-2 ]

Reference： [1]Journal of the American Chemical Society,1940,vol. 62,p. 3256
Journal of the American Chemical Society,1943,vol. 65,p. 1082

14
[ 24324-17-2 ]
[ 20615-64-9 ]

Reference： [1]RSC Advances,2016,vol. 6,p. 36728 - 36735
[2]Journal of Organic Chemistry,2001,vol. 66,p. 7907 - 7909
[3]RSC Advances,2014,vol. 4,p. 64419 - 64428

15
[ 24324-17-2 ]
[ 4425-82-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	With 1H-imidazole; PS-triphenylphosphine; iodine In dichloromethane for 0.5h; Heating / reflux;	Compound 204a:; 204aTo a dichloromethane solution (35 imL) of triphenylphosphine (polymer-supported, 3 mmol/g, 1.87 g, 5.61 mmol) was added I2 (1.42 g, 5.61 mmol). The mixture was stirred for 15 minutes. Imidazole (410 mg, 6.38 mmol) was introduced and stirred gently at room temperature for another 15 minutes. 9- Fluorenyl methanol (500 mg, 2.55 mmole) was then introduced into the reaction mixture and refluxed for 30 minutes. It was filtered through a pad of celite. The filtrate was diluted with dichloromethane (30 mL), washed with saturated Na2S2O3 (30 mL), water (30 mL) and brine (30 nriL), dried with Na2SO4 and concentrated to give the title compound in 100% yield. 1H NMR (DMSO- d6): δ 7.88 (2H, d, J=7.3Hz), 7.83 (2H, d, J=7.6Hz), 7.41 (2H, td, J=7.6, 1.1 Hz), 7.33 (2H, td, J=7.6, 1.3Hz), 6.27 (2H, s). LCMS (APCI): 179.0 (M+H+).
91.8%	With potassium hydroxide In methanol at 60℃; for 1h;
84.9%	With potassium <i>tert</i>-butylate at 60℃; for 0.333333h;

	Multi-step reaction with 2 steps 1.1: pyridine / dichloromethane / 0.17 h / 0 °C 1.2: 1.5 h / 20 °C 2.1: DBN; water / tetrahydrofuran / 1 h / 20 - 60 °C
	In hexane at 23℃; Irradiation;

Reference： [1]Current Patent Assignee: PFIZER INC - WO2006/40646, 2006, A1 Location in patent: Page/Page column 130
[2]Nakano; Takewaki; Yade; Okamoto [Journal of the American Chemical Society, 2001, vol. 123, # 37, p. 9182 - 9183]
[3]Nakano, Tamaki; Yade, Tohru [Journal of the American Chemical Society, 2003, vol. 125, # 50, p. 15474 - 15484]
[4]Vangala, Madhuri; Shinde, Ganesh P. [Beilstein Journal of Organic Chemistry, 2016, vol. 12, p. 2086 - 2092]
[5]Nageh, Hassan; Zhao, Liming; Nakayama, Akira; Hasegawa, Jun-Ya; Wang, Yue; Nakano, Tamaki [Chemical Communications, 2017, vol. 53, # 60, p. 8431 - 8434]

16
[ 108-55-4 ]
[ 24324-17-2 ]
[ 239087-66-2 ]

Yield	Reaction Conditions	Operation in experiment
61%	With dmap In dichloromethane at 20℃; for 20h;	27 Scheme 27. Preparation of rifabutin bisphosphonate conjugates 155.; [00352] 4-(((9H-Fluoren-9-yl)methoxy)carbonyl)butanoic acid (151): To a solution of glutaric anhydride (1.0 g, 8.76 mmol) and (9/-/-fluoren-9-yl)methanol (1.56 g, 7.97 mmol) in CH2CI2 (44 ml.) was added DMAP (107 mg, 0.88 mmol) and the mixture was stirred for 20 h at room temperature. The reaction mixture was concentrated, diluted with H2O and saturated NaHCOs solution and washed with ethyl acetate. The organic layer was extracted with saturated NaHCOs solution (3χ). The combined aqueous layers were acidified to pH=2 with cone. HCl solution, extracted with a 4:1 mixture of CHCl3 / /-PrOH (3χ~). The organic layers were combined, dried over MgSO4, filtered and concentrated to dryness, yielding acid 151 as a white solid (1.5 g, 61%). 1H NMR (400 MHz, CDCI3) δ 1.95 (quint, J=I.3 Hz, 2H), 2.40 (t, J=7.3 Hz, 2H), 2.47 (t, J=7.3 Hz, 2H), 4.21 (t, J=6.9 Hz, 1 H), 4.43 (d, J=7.0 Hz, 2H), 7.32 (dt, J=IA, 1.1 Hz, 2H), 7.41 (t, J=7.4 Hz, 2H), 7.59 (d, J=7.5 Hz, 2H), 7.78 (d, J=7.5 Hz, 2H).
	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 18h;

Reference： [1]Current Patent Assignee: Novartis (w/o Sandoz); NOVARTIS AG - WO2010/19511, 2010, A2 Location in patent: Page/Page column 155
[2]Griffin, John H.; Linsell, Martin S.; Nodwell, Matthew B.; Chen, QiQi; Pace, John L.; Quast, Kelly L.; Krause, Kevin M.; Farrington, Lesley; Wu, Terry X.; Higgins, Deborah L.; Jenkins, Thomas E.; Christensen, Burton G.; Judice, J. Kevin [Journal of the American Chemical Society, 2003, vol. 125, # 21, p. 6517 - 6531]

17
[ 24324-17-2 ]
[ 486-25-9 ]

Yield	Reaction Conditions	Operation in experiment
86%	With sodium bromate; 1-n-butyl-3-methylimidazolim bromide at 70℃; for 140h;
81%	With N-hydroxyphthalimide; oxygen; 3-chloro-benzenecarboperoxoic acid; cobalt(III) acetylacetonate In ethyl acetate at 60℃; for 6h; Schlenk technique; Green chemistry;
78%	With dipotassium peroxodisulfate; V₂O₅/TiO₂ In water; acetonitrile at 80℃; Sealed tube; Green chemistry;

75%	With manganese(IV) oxide; 2,2'-azobis(isobutyronitrile); potassium hydroxide In cyclohexane; acetone for 24h; Reflux;	substrate H (entry 32, table 3) 131 mg (0.667 mmol, 1 eq.) 9-fluorenyl methanol were dissolved in 300 mL cyclohexane. 116 mg (1.33 mmol, 2 eq.) Mn(IV) oxide, 112 mg (2 mmol, 3 eq.) KOH, 11 mg (0.066 mmol, 0.1 eq.) AIBN and 5 drops of acetone were added. The suspension was heated at reflux for 1 day. After cooling, the suspension was filtered through kieselguhr and the solvent removed. The product was isolated by column chromatography (eluent: cyclohexanes: EtOAc = 50: 1 → 20: 1 → 10: 1 → 1: 1).yellow solid powder; m.p. 80-82 oC (81-83 oC); 1H NMR (300 MHz, CDCl3): δ 7.65 (d, J = 7.4 Hz, 2H), 7.48-7.45 (m, 4H), 7.28-7.26 (m, 2H). 13C NMR (75 MHz, CDCl3): δ 193.8, 144.3, 134.6, 134.0, 129.0, 124.2, 120.2.
63%	With molecular sieve; pyridinium chlorochromate In dichloromethane at 20℃; for 12h;
87 %Chromat.	With oxygen; potassium carbonate In o-xylene at 20℃; for 9h;
	With potassium carbonate In o-xylene at 20℃; for 14h;	3.3. Oxidation of alcohols; General procedure General procedure: In a typical reaction, an alcohol (1.0 mmol) was added to a twoneckedflask containing MnO2silk (0.09 g, 10 mol% of MnO2),K2CO3 (0.50 mmol), and o-xylene (5.0 mL) and stirred under airblowing at room temperature. The progress of the reaction was followedby TLC and GC method. After completion of reaction and filtrationof mixture, the filtrate was analyzed by GC method.
89 %Chromat.	With potassium hydroxide In o-xylene at 144℃; for 3h; Green chemistry;

Reference： [1]Location in patent: experimental part Shaabani, Ahmad; Farhangi, Elham; Rahmati, Abbas [Monatshefte fur Chemie, 2008, vol. 139, # 8, p. 905 - 908]
[2]Li, Tingting; Hammond, Gerald B.; Xu, Bo [Chemistry - A European Journal, 2021, vol. 27, # 38, p. 9737 - 9741]
[3]Upadhyay, Rahul; Kumar, Shashi; Maurya, Sushil K. [ChemCatChem, 2021, vol. 13, # 16, p. 3594 - 3600]
[4]Havare, Nizam [Arkivoc, 2020, vol. 2020, # 6, p. 247 - 261]
[5]Fernandes, Rodney A.; Kumar, Pradeep [Tetrahedron Letters, 2003, vol. 44, # 6, p. 1275 - 1278]
[6]Shaabani, Ahmad; Hezarkhani, Zeinab; Badali, Elham [RSC Advances, 2015, vol. 5, # 76, p. 61759 - 61767]
[7]Shaabani, Ahmad; Hezarkhani, Zeinab; Badali, Elham [Polyhedron, 2016, vol. 107, p. 176 - 182]
[8]Shaabani, Ahmad; Rashidi Vahid, Adina; Shaabani, Shabnam; Mohammadian, Reza; Nazeri, Mohammad Taghi; Keramati Nejad, Mina [Applied Organometallic Chemistry, 2018, vol. 32, # 10]

18
[ 13726-67-5 ]
[ 24324-17-2 ]
[ 402717-36-6 ]

Reference： [1]Macromolecules,2002,vol. 35,p. 746 - 759

19
[ 2389-45-9 ]
[ 24324-17-2 ]
[ 220064-87-9 ]

Yield	Reaction Conditions	Operation in experiment
86.5%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;
	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide
	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide

Reference： [1]Miyazaki, Anna; Tsuda, Yuko; Fukushima, Shoji; Yokoi, Toshio; Vántus, Tibor; Bökönyi, Gyöngyi; Szabó, Edit; Horváth, Anikó; Kéri, György; Okada, Yoshio [Journal of Medicinal Chemistry, 2008, vol. 51, # 16, p. 5121 - 5124]
[2]Miyazaki, Anna; Yokoi, Toshio; Tachibana, Yoshifumi; Enomoto, Riyo; Lee, Eibai; Bokonyi, Gyongyi; Keri, Gyorgy; Tsuda, Yuko; Okada, Yoshio [Tetrahedron Letters, 2004, vol. 45, # 33, p. 6323 - 6327]
[3]Location in patent: scheme or table Miyazaki, Anna; Tsuda, Yuko; Fukushima, Shoji; Yokoi, Toshio; Vantus, Tibor; Boekoenyi, Gyoengyi; Szabo, Edit; Horvath, Aniko; Keri, Gyoergy; Okada, Yoshio [Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 23, p. 6199 - 6201]

20
[ 24324-17-2 ]
[ 40350-83-2 ]
Boc-Hyp(Bzl)-OFm [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 5677 - 5680

21
[ 24324-17-2 ]
[ 800388-78-7 ]
[ 800388-80-1 ]

Yield	Reaction Conditions	Operation in experiment
64%	Stage #1: (7R,8S)-7-((1S,2S)-1-Allyloxycarbonyl-2-methyl-butylamino)-8-(tert-butyl-dimethyl-silanyloxy)-4-[(S)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-7,8-dihydro-quinoline-2-carboxylic acid With 2,4,6-trichlorobenzoyl chloride; triethylamine In toluene at 25℃; for 12h; Stage #2: 9-Fluorenylmethanol With dmap In toluene at 25℃; for 12h;
64%	Stage #1: (7R,8S)-7-((1S,2S)-1-Allyloxycarbonyl-2-methyl-butylamino)-8-(tert-butyl-dimethyl-silanyloxy)-4-[(S)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-7,8-dihydro-quinoline-2-carboxylic acid With 2,4,6-trichlorobenzoyl chloride; triethylamine In toluene at 25℃; for 4h; Stage #2: 9-Fluorenylmethanol With dmap In toluene at 25℃; for 14h;

Reference： [1]Nicolaou; Zak, Mark; Safina, Brian S.; Lee, Sang Hyup; Estrada, Anthony A. [Angewandte Chemie - International Edition, 2004, vol. 43, # 38, p. 5092 - 5097]
[2]Nicolaou; Safina, Brian S.; Zak, Mark; Lee, Sang Hyup; Nevalainen, Marta; Bella, Marco; Estrada, Anthony A.; Funke, Christian; Zecri, Frederic J.; Bulat, Stephan [Journal of the American Chemical Society, 2005, vol. 127, # 31, p. 11159 - 11175]

22
[ 921-26-6 ]
[ 24324-17-2 ]
[ 197709-11-8 ]

Yield	Reaction Conditions	Operation in experiment
72%	With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0 - 20℃; for 3h;
53%	With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 1h;
	With N-ethyl-N,N-diisopropylamine In tetrahydrofuran for 10h; Schlenk technique; Cooling with ice;	Fromtheobtainedliquid,analiquotwastaken(2.0g,10mml).ThiswasdissolvedindryTHF(40ml)andDIPEA(3.5ml,2equiv)wasadded.Thesolutionwascooledinanicebathand(9H--fluoren--9--yl)methanol(3.92g,2equiv)indryTHF(10ml)wasadded.Thesolutionwasstirredfor10hduringwhichawhiteprecipitateformed.Thereactionwaspouredintoaqueousphosphatebuffer(1M,pH=7)andextractedwithethylacetate(4x50ml).Thecombinedorganicextractswerewashedwiththesamephosphatebuffer,brine,driedandevaporated.Thecrudeproductwasusedwithoutfurtherpurificationduetoitssensitivity.31PNMR(162MHz,CDCl3)δ148.01.

Reference： [1]Lambrecht, Michael J.; Brichacek, Matthew; Barkauskaite, Eva; Ariza, Antonio; Ahel, Ivan; Hergenrother, Paul J. [Journal of the American Chemical Society, 2015, vol. 137, # 10, p. 3558 - 3564]
[2]Bialy, Laurent; Waldmann, Herbert [Chemistry - A European Journal, 2004, vol. 10, # 11, p. 2759 - 2780]
[3]Jain, Samta; Caforio, Antonella; Fodran, Peter; Lolkema, Juke S.; Minnaard, Adriaan J.; Driessen, Arnold J.M. [Chemistry and Biology, 2014, vol. 21, # 10, p. 1392 - 1401]

23
[ 20615-64-9 ]
[ 24324-17-2 ]

Reference： [1]Journal of Chemical Thermodynamics,2004,vol. 36,p. 79 - 86

24
[ 511547-46-9 ]
[ 24324-17-2 ]
[ 869081-67-4 ]

Yield	Reaction Conditions	Operation in experiment
89%	With dmap; benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane
89%	With dmap; benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane at 20℃; for 1h;
86%	With dmap; benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane

Reference： [1]Amorin, Manuel; Brea, Roberto J.; Castedo, Luis; Granja, Juan R. [Organic Letters, 2005, vol. 7, # 21, p. 4681 - 4684]
[2]Amorin, Manuel; Castedo, Luis; Granja, Juan R. [Chemistry - A European Journal, 2005, vol. 11, # 22, p. 6543 - 6551]
[3]Amorin, Manuel; Brea, Roberto J.; Castedo, Luis; Granja, Juan R. [Heterocycles, 2006, vol. 67, # 2, p. 575 - 583]

25
[ 869116-60-9 ]
[ 24324-17-2 ]
[ 869116-61-0 ]

Yield	Reaction Conditions	Operation in experiment
92%	With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 2h;

Reference： [1]Brea, Roberto J.; Amorin, Manuel; Castedo, Luis; Granja, Juan R. [Angewandte Chemie - International Edition, 2005, vol. 44, # 35, p. 5710 - 5713]

26
[ 24324-17-2 ]
[ 616867-28-8 ]

Reference： [1]Journal of the American Chemical Society,2003,vol. 125,p. 12106 - 12107

27
[ 24324-17-2 ]
[ 117014-32-1 ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 2555 - 2561
[2]Synthetic Communications,1992,vol. 22,p. 1001 - 1005
[3]Synthesis,1990,p. 119 - 122

28
[ 24324-17-2 ]
[ 82911-78-2 ]

Reference： [1]Canadian Journal of Chemistry,1982,vol. 60,p. 976 - 980

29
[ 24324-17-2 ]
[ 82911-79-3 ]

Reference： [1]Canadian Journal of Chemistry,1982,vol. 60,p. 976 - 980

30
[ 24324-17-2 ]
[ 84418-43-9 ]

Reference： [1]Synthesis,1988,p. 992 - 994

31
[ 24324-17-2 ]
[ 35661-51-9 ]

Reference： [1]Journal of Organic Chemistry,1972,vol. 37,p. 3404 - 3409

32
[ 24324-17-2 ]
[ 598-21-0 ]
[ 857722-29-3 ]

Yield	Reaction Conditions	Operation in experiment
62%	With triethylamine In dichloromethane at 20℃; for 18h;	15.1 Step 1 To the solution of (9H-fluoren-9-yl)methanol (2.0 g, 10.2 mmol) and 2-bromoacetyl bromide (4.08 g, 20.4 mmol) in DCM (40 mL) was added TEA (3.09 g, 30.6 mmol), and the mixture was stirred at room temperature for 18 h. The reaction mixture was quenched with water (40 mL), the organic layer was separated, and the aqueous layer extracted with DCM (3 x 40 mL). The combined organic layers were washed with brine, dried over Na2SO4and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by flash column chromatography on silica (0-15% tert-butyl methyl ether /petroleum ether) to give (9H-fluoren-9- yl)methyl 2-bromoacetate (2.0 g, 62% yield) as yellow oil. LCMS m/z 339.0 (M+Na)+(ES+).
39.8%	With triethylamine In dichloromethane for 1h; Cooling with ice;	41 Synthesis of compound Pseudouridine 1 -(2-ethanoic acid -Fm) (03601015034- Fm): 9-Fluorenyl methanol (10 g, 1 eq) was dissolved in 100 mL of dichlormethane, and triethylamine (6.14 g, 1 .19 eq) was added. The reaction mixture was cooled in ice bath, and a solution of bromoacetyl bromide (10.3 g, 1 eq) in 10 m L methylene chloride was added under stirring over 1 h. The cloudy mixture was warmed to room temperature, and stirred overnight. The mixture was washed with water (100 mL x 3) and brine. The combined organic phase was dried and concentrated under reduced pressure. The crude product thus obtained was purified via silica gel chromatography (PE:EA = 300:1 -50:1 ) giving 6.4 g product 102 as a light yellow solid in 39.8% yield.
39.8%	With triethylamine In dichloromethane at 20℃; Cooling with ice;	34; 41 ynt es s o romoacet c c m ster 102 : 9- uoreny met ano 10 g, 1 eq was solved in 1 00 mL of dichlormethane, and triethylamine (6.1 4 g, 1 .1 9 eq) was added. The reaction xture was cooled in ice bath, and a solution of bromoacetyl bromide (10.3 g, 1 eq) in 1 0 mL thylene chloride was added under stirring over 1 h. The cloudy mixture was warmed to room mperature, and stirred overnight. The mixture was washed with water (1 00 mL x 3) and brine. The mbined organic phase was dried and concentrated under reduced pressure. The crude product s obtained was purified via silica gel chromatography (PE:EA = 300:1 -50:1 ) giving 6.4 g product 2 as a light yellow solid in 39.8% yield.

In tetrahydrofuran at 0℃;

13 Bromoacetic acid 9H-fluoren-9-ylmethyl ester was prepared from bromoacetyl bromide and 9Sfluorenylmethanol in dry THF at 0°C. Boc-butyl-PAMA-OFm ( [ (4-tert-butoxy- carbonylamino-butyl)-pyridin-2-ylmethyl-amino]-acetic acid 9Sfluoren-9-ylmethyl ester) was prepared from Boc-NH- (CH2) 4NH2, pyridine-2-aldehyde and bromoacetic acid 9S fluoren-9-ylmethyl ester according to the procedure used by Schibli et al. (Nucl. Med. Biol. 2003,30, 465) for the synthesis of Boc-pentyl-PAMA-OMe.

Reference： [1]Current Patent Assignee: SITRYX THERAPEUTICS - WO2022/38365, 2022, A2 Location in patent: Page/Page column 73
[2]Current Patent Assignee: MODERNA THERAPEUTICS INC - WO2014/93924, 2014, A1 Location in patent: Page/Page column 275
[3]Current Patent Assignee: MODERNA THERAPEUTICS INC - WO2015/196128, 2015, A2 Location in patent: Page/Page column 616
[4]Current Patent Assignee: SOLIDAGO AG; UNIVERSITY OF ZURICH; PAUL SCHERRER INSTITUTE - WO2005/61527, 2005, A1 Location in patent: Page/Page column 22-23

33
[ 24324-17-2 ]
[ 38818-50-7 ]
[ 866366-63-4 ]

Yield	Reaction Conditions	Operation in experiment
95%	With pyridine; In tetrahydrofuran; at 20℃;	4-Chloro-3-nitrobenzoyl chloride (1.13 equiv. , 133.2 mmol, 29.3 g) was dissolved in dry THF and pyridine (2 equiv. , 235.8 mmol, 19.0 ml) was added. A white precipitate formed immediately upon addition of pyridine. A solution of 9-fluorenemethanol (1 equiv. , 117.9 mmol, 23.1 g) in dry THF was added and the resulting mixture was stirred at room temperature over night. The solvent was removed in vacuo and the resulting solid was mixed with diethyl ether and filtered. The solid was then washed several times with ether to achieve the pure desired product. Yield : 95%.

Reference： [1]Patent: WO2005/92872,2005,A1 .Location in patent: Page/Page column 30

34
[ 13734-36-6 ]
[ 24324-17-2 ]
[ 530-62-1 ]
[ 180312-46-3 ]

Yield	Reaction Conditions	Operation in experiment
73%	With hydrogenchloride In 1,4-dioxane; dichloromethane	11 Preparation of sarcosine-O-fluorenylmethyl ester hydrochloride salt. STR32 To a solution of Boc-sarcosine (30 g, 158 mmole) in 500 mL dichloromethane was added with stirring carbonyl diimidazole (25.7 g, 158 mmole). After 15 minutes, 9-fluorene methanol (29.5 g, 150 mmole) was added and stirring was continued. After 16 hours, the reaction mixture was diluted with 1200 mL ethyl acetate and extracted with 300 mL each of water, 1 M aqueous hydrochloric acid, water, saturated aqueous sodium bicarbonate and brine. The organic phase was dried over anhydrous magnesium sulfate, filtered and the solvent removed in vacuo. The resulting oil was dissolved in 500 mL dichloromethane and treated with 100 mL of a 4.0M solution of hydrochloric acid in dioxane. After 12 hours, the title compound was precipitated by pouring the reaction mixture into ether (1000 mL) with vigorous stirring. The precipitate was filtered and dried in vacuo to provide 35 g (73% yield) of the title compound as an off-white powder.
73%	With hydrogenchloride In 1,4-dioxane; dichloromethane	11 Preparation of sarcosine-O-fluorenylmethyl ester hydrochloride salt. STR31 To a solution of Boc-sarcosine (30 g, 158 mmole) in 500 mL dichloromethane was added with stirring carbonyl diimidazole (25.7 g, 158 mmole). After 15 minutes, 9-fluorene methanol (29.5 g, 150 mmole) was added and stirring was continued. After 16 hours, the reaction mixture was diluted with 1200 mL ethyl acetate and extracted with 300 mL each of water, 1M aqueous hydrochloric acid, water, saturated aqueous sodium bicarbonate and brine. The organic phase was dried over anhydrous magnesium sulfate, filtered and the solvent removed in vacuo. The resulting oil was dissolved in 500 mL dichloromethane and treated with 100 mL of a 4.0M solution of hydrochloric acid in dioxane. After 12 hours, the title compound was precipitated by pouring the reaction mixture into ether (1000 mL) with vigorous stirring. The precipitate was filtered and dried in vacuo to provide 35 g (73% yield) of the title compound as an off-white powder.

Reference： [1]Current Patent Assignee: NANJING XINJIEKOU DEPARTMENT STORE CO., LTD. - US6025472, 2000, A
[2]Current Patent Assignee: NANJING XINJIEKOU DEPARTMENT STORE CO., LTD. - US5696231, 1997, A

35
chlorocarbonic acid-(1,1,2,2-tetrachloro-ethyl ester) [ No CAS ]
[ 24324-17-2 ]
9-fluorenylmethyl carbonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	With pyridine In dichloromethane	9 Preparation of 1, 2, 2, 2 tetrachloroethyl and 9-fluorenylmethyl carbonate STR19 EXAMPLE 9 Preparation of 1, 2, 2, 2 tetrachloroethyl and 9-fluorenylmethyl carbonate STR19 6.7 (0.027 mole) of 1, 2, 2, 2 tetrachloroethyl chloroformate are added at one time to a solution of 9-fluorenylmethanol (4.9 g; 0.025 mole) in 50 ml dichloromethane. The mixture is cooled to 0° C. and 2.2 ml of pyridine are added drop by drop. The mixture is stirred for four hours at 0° C. 50 ml of dichloromethane are then added and the organic phase washed twice with 50 ml of chilled water. Drying takes place over magnesium sulfate and the solvent is evaporated. The residue is crystallized from hexane and 9.3 g of the desired carbonate obtained (yield 98%). m.p.=98°-100° C. IR: νC=0 1750 cm-1 NMR H1: (CDC13, TMS) 4.5 ppm CH2 --0; 6.75 ppm STR20

Reference： [1]Current Patent Assignee: AURELIUS SE & CO KGAA - US4960881, 1990, A

36
[ 13641-96-8 ]
[ 24324-17-2 ]
[ 909781-41-5 ]

Yield	Reaction Conditions	Operation in experiment
71%	With 2,6-di-tert-butyl-4-methyl-phenol In benzene for 9h; Heating / reflux;	1.B Synthesis of Acrylate MonomerAn acrylate monomer was synthesized according to the formula (6) below. 60 mL of dehydrated benzene and 100 mg of di-n-butyltin dilaurylate as a catalyst were added to 2.08 g (10.6 mmol) fluorenylmethanol synthesized according to the formula (5). Thereafter, 1.41 g (10 mmol) of 2-isocyanatoethyl acrylate and 20 mL of a benzene solution containing 50 mg of 2,6-di-tert-butyl-p-cresol as a polymerization inhibitor were slowly added dropwise thereto under refluxing. After refluxing for 9 hours, the mixture was cooled to room temperature, and the solvent was distilled off. A small amount of diethyl ether and a large amount of hexane were added to the resulting brown oil. Recrystallization was effected by storing in a freezer to obtain an acrylate monomer in a white crystal form. It was confirmed that the resulting compound had the aforementioned structure represented by the formula (6) by measuring with 1H-NMR. The melting point and the measurement result of 1H-NMR are shown below.Yield: 71%Melting point: 101-103° C.1H-NMR (270 MHz, CDCl3) δ (ppm): 3.3-3.7 (2H, m, NH-CH2), 4.0-4.6 (4H, m, O-CH2), 5.06 (1H, s, NH), 5.85 (1H, d, J=10.3 Hz, CCH2), 6.0-6.2 (1H, m, CCH), 6.44 (1H, d, J=17.0 Hz, CCH2), 7.1-7.5 (4H, m, ArH), 7.57 (2H, d, J=7.3 Hz, ArH), 7.76 (2H, d, J=7.3 Hz, ArH)

Reference： [1]Current Patent Assignee: SEKISUI CHEMICAL CO., LTD. - US2008/200580, 2008, A1 Location in patent: Page/Page column 7-8

37
[ 24324-17-2 ]
[ 37553-65-4 ]
[ 1038618-28-8 ]

Yield	Reaction Conditions	Operation in experiment
70%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane

Reference： [1]Tan, Li; Ma, Dawei [Angewandte Chemie - International Edition, 2008, vol. 47, # 19, p. 3614 - 3617]

38
[ 660449-93-4 ]
[ 24324-17-2 ]
[ 660450-83-9 ]

Yield	Reaction Conditions	Operation in experiment
45%	Stage #1: 3-[(tert-butoxycarbonyl)amino]methyl}-4-(4-methylphenyl)-2-(2-methylpropyl)quinoline-6-carboxylic acid With diphenyl phosphoryl azide; triethylamine In DMF (N,N-dimethyl-formamide) at 20℃; for 1h; Stage #2: 9-Fluorenylmethanol In toluene for 13h; Heating / reflux;	78.1 Example 78; [N- [3- (AMINOMETHYL)-2-ISOBUTYL-4- (4-METHYLPHENYL)-6-] quinolinyl] acetamide dihydrochloride 1) A mixture of [3-[(TERT-BUTOXYCARBONYL) AMINO] METHYL}-2-] isobutyl-4- (4-methylphenyl) quinoline-6-carboxylic acid (Example 45 [(1))] (2.24 g, 5.0 mmol), diphenylphosphoryl azide (1.3 ml, 6.0 mmol), triethylamine (0.84 ml, 6.0 mmol) and N, N- dimethylformamide (20 ml) was stirred at room temperature for 1 hr. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and toluene (30 ml) was added to the residue. The mixture was heated under reflux for 1 hr. The obtained mixture was cooled to room temperature and 9-fluorenylmethanol (1.47 g, 7.5 mmol) was added. The mixture was heated under reflux for [12 HRS.] The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give 9H-fluoren-9-ylmethyl [3- [ [ (TERT-] butoxycarbonyl) amino] [METHYL]-2-ISOBUTYL-4- (4-METHYLPHENYL)-6-] quinolinylcarbamate (1.45 [G,] yield [45%)] as an amorphous form. 1H-NMR [(CDC13)] [G] : 1.02 (6H, [D,] J = 6.6 Hz), 1.41 (9H, s), 2.30- 2.46 (4H, m), 2.93 (2H, d, J = 7.2 Hz), 4.03-4. 21 (3H, m), 4.25 (2H, d, J = 4.8 Hz), 4.32 [(1H,] bs), 4.49 (2H, d, [J] = 6.6 Hz), 6.76 [(1H,] bs), 7.07-7. 12 (3H, m), 7.25-7. 41 (5H, [M),] 7.53-7. 62 (3H, m), 7.73-7. 77 (3H, m), 7.99 [(1H,] d, J [=-9.] 0 Hz).

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2004/14860, 2004, A2 Location in patent: Page 177-178

39
[ 24324-17-2 ]
[ 874-60-2 ]
[ 1036648-29-9 ]

Yield	Reaction Conditions	Operation in experiment
91%	With N,N,N,N,-tetramethylethylenediamine In dichloromethane at -78℃; for 0.5h; Inert atmosphere;
91%	With N,N,N,N,-tetramethylethylenediamine In dichloromethane at -78℃; for 0.5h;
91%	With N,N,N,N,-tetramethylethylenediamine In dichloromethane at -78℃; for 0.5h; Inert atmosphere;

Reference： [1]Lam, Kevin; Marko, Istvan E. [Organic Letters, 2008, vol. 10, # 13, p. 2773 - 2776]
[2]Lam, Kevin; Marko, Istvan E. [Chemical Communications, 2009, # 1, p. 95 - 97] Lam, Kevin; Marko, Istvan E. [Organic Letters, 2009, vol. 11, # 13, p. 2752 - 2755]
[3]Location in patent: experimental part Lam, Kevin; Markó, István E. [Tetrahedron, 2009, vol. 65, # 52, p. 10930 - 10940]

40
[ 1162648-59-0 ]
[ 24324-17-2 ]

Yield	Reaction Conditions	Operation in experiment
99%	With methanol; 1,3-disulfonic acid imidazolium hydrogen sulfate at 20℃; for 0.0833333h; Green chemistry;	General procedure for the deprotection of trimethylsilyl ethers General procedure: A mixture of the substrate (1 mmol), ionic liquid [Dsim]HSO4 (6.5 mg, ∼0.02 mmol) in methanol (2 mL) was stirred at room temperature. After completion of the reaction (monitored by TLC), solvent was evaporated, water (1 mL) was added to the mixture, and stirred vigorously. Decantation of the mixture gave almost pure product(s). The products were characterized by comparison of their IR and NMR data. The ionic liquid was dried at 65 ◦C under vacuum to remove moisture, and then reused.
94%	With rice husk ash supported on anatase-phase titania nanoparticles nanocomposite In methanol at 20℃; for 0.05h;
92%	With methanol; vanadium hydrogen sulfate at 20℃; for 0.0833333h;

91%	With poly (ethylene glycol)-sulfonated sodium montmorillonite nanocomposite In methanol at 20℃; for 0.133333h;	General procedure for deprotection of silyl ethers General procedure: A mixture of the substrate (1 mmol) and the PEG-SANMnanocomposite (8 mg) in methanol (2 mL) was stirred at roomtemperature. After completion of the reaction (monitored byTLC), the catalyst was filtered off and the solvent was evaporatedunder reduced pressure. The crude product was purifiedby column chromatography on silica gel to yield pure alcoholsand phenols.
85%	With methanol at 20℃; for 0.0833333h;	2.5. General procedure for deprotection of trimethylsilyl ethers General procedure: A mixture of the substrate (1 mmol) and TiO2-HClO4 (5 mg) in methanol (1 mL) was stirred at room temperature. After completion of the reaction (indicated by TLC), the catalyst was filtered off and the solvent was evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel to afford pure alcohols and phenols (Table 2).

Reference： [1]Shirini, Farhad; Khaligh, Nader Ghaffari; Akbari-Dadamahaleh, Somayeh [Journal of Molecular Catalysis A: Chemical, 2012, vol. 365, p. 15 - 23]
[2]Seddighi, Mohadeseh; Shirini, Farhad; Goli-Jolodar, Omid [RSC Advances, 2016, vol. 6, # 28, p. 23564 - 23570]
[3]Location in patent: experimental part Shirini, Farhad; Zolfigol, Mohammad Ali; Abedini, Masoumeh; Sakhaei, Ali Reza [Journal of the Chinese Chemical Society, 2008, vol. 55, # 5, p. 943 - 946]
[4]Shirini, Farhad; Shojaei, Abdollah Fallah; Heirati, Seyedeh Zahra Dalil [Phosphorus, Sulfur and Silicon and the Related Elements, 2016, vol. 191, # 6, p. 944 - 951]
[5]Shirini, Farhad; Atghia, Seyyed Vahid; Jirdehi, Mojtaba Ghazi [Catalysis Communications, 2012, vol. 18, p. 5 - 10]

41
[ 24324-17-2 ]
[ 999-97-3 ]
[ 1162648-59-0 ]

Yield	Reaction Conditions	Operation in experiment
98%	With poly(4-vinylpyridine) In acetonitrile at 20℃; for 0.0833333h;
96%	With 1,3-disulfonic acid imidazolium hydrogen sulfate In neat (no solvent) at 20℃; for 0.0333333h; Green chemistry;	General procedure for O-silylation of alcohols and phenols with HMDS in the presence of [Dsim]HSO4 ionic liquid General procedure: Ionic liquid [Dsim]HSO4 (6.5 mg, ∼0.02 mmol) was added to a stirred mixture of alcohol, phenol or naphthol (1.0 mmol) and HMDS (80 mg, 0.5 mmol) at room temperature under solvent free conditions. After completion of the reaction (monitored by TLC, It should be noted that when addition of HMDS is finished stirring of the mixture is stopped after 1 min. TLC showed that in most of the cases the reaction is completed immediately after the addition of HMDS), the product was extracted with Et2O and the ionic liquid was recovered and was dried at 65 ◦C under vacuum to remove moisture, and then reused. Evaporation of the solvent under reduced pressure gave the highly pure product without further purification. The desired pure products were characterized by comparison of their IR, NMR and MS data as well as boiling poin twith those of known compounds
95%	With niobium pentachloride In dichloromethane at 20℃; for 0.0833333h;

95%	With 3-methyl-1-sulfonic acid imidazolium hydrogen sulfate at 20℃; for 0.05h; Neat (no solvent);
95%	With succinimide-N-sulfonic acid In acetonitrile at 20℃; for 0.05h;
90%	With poly (ethylene glycol)-sulfonated sodium montmorillonite nanocomposite In acetonitrile at 20℃; for 0.116667h;	General procedure for silylation of the alcohols andphenols General procedure: HMDS (0.5 mmol) was added to a stirring mixture of the substrate(1 mmol), and the PEG-SANM nanocomposite (8 mg)in CH3CN (2 mL) at room temperature. The progress of thereaction was monitored by TLC. After completion of the reaction,the mixture was filtered and the recovered catalyst waswashed with acetonitrile and acetone, dried at 80°C and reusedfor the same reaction. Evaporation of the solvent gave almostpure product. Further purification proceeded by recrystallizationto yield pure silyl ether.
89%	With saccharin sulfonic acid In acetonitrile at 20℃; for 0.166667h; chemoselective reaction;
89%	In acetonitrile at 20℃; for 0.0333333h;	2.4. General procedure for trimethylsilylation of alcohols and phenols General procedure: To a stirring mixture of the substrate (1 mmol), and TiO2-HClO4 (5 mg) in CH3CN (3 mL), HMDS (120 mg, 0.75 mmol) was added at room temperature. The progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was filtered and the filtrate was washed with acetonitrile (5 mL). Evaporation of the solvent gave almost pure product(s). Further purification proceeded by bulb to bulb distillation under reduced pressure or recrystallization to afford pure silyl ether (Table 2).
89%	With rice husk ash supported on anatase-phase titania nanoparticles nanocomposite In acetonitrile at 50℃; for 0.0166667h; chemoselective reaction;
85%	With vanadium hydrogen sulfate In acetonitrile at 20℃; for 0.25h; chemoselective reaction;
79%	at 20℃; for 0.7h; Neat (no solvent); Air atmosphere;	4.1. Representative procedure of the non-catalysed reaction of phenols and alcohols with HMDS under SFRC (small scale) General procedure: To phenol 1a (0.173 g, 1 mmol) or alcohol 3a (0.108 g, 1 mmol) HMDS (0.089 g, 0.55 mmol) was added, and the mixture was stirred at room temperature until the complete consumption of the starting material (TLC check). The excess of HMDS was distilled off under reduced pressure and nearly pure products were obtained. Products can be purified with column chromatography and/or distillation.

Reference： [1]Shirini, Farhad; Khaligh, Nader Ghaffari [Journal of the Iranian Chemical Society, 2012, vol. 9, # 4, p. 495 - 502]
[2]Shirini, Farhad; Khaligh, Nader Ghaffari; Akbari-Dadamahaleh, Somayeh [Journal of Molecular Catalysis A: Chemical, 2012, vol. 365, p. 15 - 23]
[3]Location in patent: experimental part Hou, Jun-Tao; Chen, Hong-Li; Zhang, Zhan-Hui [Phosphorus, Sulfur and Silicon and the Related Elements, 2011, vol. 186, # 1, p. 88 - 93]
[4]Location in patent: experimental part Khaligh, Nader Ghaffari [Journal of Molecular Catalysis A: Chemical, 2011, vol. 349, # 1-2, p. 63 - 70]
[5]Location in patent: experimental part Shirini; Khaligh, Nader Ghaffari [Phosphorus, Sulfur and Silicon and the Related Elements, 2011, vol. 186, # 11, p. 2156 - 2165]
[6]Shirini, Farhad; Shojaei, Abdollah Fallah; Heirati, Seyedeh Zahra Dalil [Phosphorus, Sulfur and Silicon and the Related Elements, 2016, vol. 191, # 6, p. 944 - 951]
[7]Location in patent: experimental part Shirini, Farhad; Zolfigol, Mohammad Ali; Abedini, Masoumeh [Monatshefte fur Chemie, 2009, vol. 140, # 1, p. 61 - 64]
[8]Shirini, Farhad; Atghia, Seyyed Vahid; Jirdehi, Mojtaba Ghazi [Catalysis Communications, 2012, vol. 18, p. 5 - 10]
[9]Seddighi, Mohadeseh; Shirini, Farhad; Goli-Jolodar, Omid [RSC Advances, 2016, vol. 6, # 28, p. 23564 - 23570]
[10]Location in patent: experimental part Shirini, Farhad; Zolfigol, Mohammad Ali; Abedini, Masoumeh; Sakhaei, Ali Reza [Journal of the Chinese Chemical Society, 2008, vol. 55, # 5, p. 943 - 946]
[11]Location in patent: experimental part Jereb, Marjan [Tetrahedron, 2012, vol. 68, # 20, p. 3861 - 3867]

42
[ 24324-17-2 ]
[ 20724-73-6 ]
[ 1185923-47-0 ]

Yield	Reaction Conditions	Operation in experiment
		Reference Example 1 (R6=Et)Step 1:; 5'-O-[[[(1S)-2-ethoxy-1-methyl-2-oxo ethyl]amino](9H-fluoren-9-ylmethoxy)phosphinyl]-<strong>[20724-73-6]2'-C-methylcytidine</strong>Bisphenyl phosphite was dissolved in pyridine (0.3 M) and a solution of fluorenylmethyl alcohol in pyridine (0.3 M) was added. The mixture was stirred at 0 C. for 20 min. Then a solution of 2'-C-methyl-cytidine in pyridine (0.3M) was added at 0 C. The resulting solution was warmed to 40 C. and stirred for 1 h at this temperature. The solvent was evaporated and the residue dissolved in DMA (0.19M). The resulting solution was added to a solution of L-alanine-ethylester hydrochloride (1.2 eq.) and Et3N (2.0 eq.) in iPrOH:CCl4 (0.24 M, 10:1). The mixture was stirred for 10 min at 0 C. and then the solvent was evaporated. The residue was dissolved in EtOAc and water. The aqueous phase was extracted three times with EtOAc, the combined organic phases were washed with brine and dried over Na2SO4. The crude product was purified by RP-HPLC (stationary phase: column XTerra C18, 5 mum, 19×150 mm. Mobile phase: MeCN/H2O 5 mM AMBIC). Fractions containing the pure compound were freeze-dried to afford the title compound as white powder and as a mixture of diastereoisomers 1:1. MS (ES+) m/z 615 (M+H)-

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 5394 - 5407
[2]Patent: US2010/152128,2010,A1 .Location in patent: Page/Page column 13

43
[ 24324-17-2 ]
[ 88050-17-3 ]
[ 1325728-11-7 ]

Reference： [1]Journal of Polymer Science, Part A: Polymer Chemistry,2011,vol. 49,p. 3783 - 3796

44
[ 1353724-12-5 ]
[ 24324-17-2 ]

Yield	Reaction Conditions	Operation in experiment
91%	With Amberlite 120-H resin In methanol for 3h; Reflux;	Procedure for the deprotection of tert-butyl ether Compound 1b (1 g) was taken in 5 mL of methanol in a 50 mL round bottom flask and 1 g of amberlite resin 120-H was added. Reaction mass was refluxed for 5 h, filtered and washed with methanol. Methanol was removed under vacuum to yield pure compound 1a.

Reference： [1]Location in patent: experimental part Mallesha; Prahlada Rao; Suhas; Channe Gowda [Tetrahedron Letters, 2012, vol. 53, # 6, p. 641 - 645]

45
[ 1634-04-4 ]
[ 24324-17-2 ]
[ 1353724-12-5 ]

Yield	Reaction Conditions	Operation in experiment
94%	With sulfuric acid at 25℃; for 4h; Molecular sieve;	Procedure for the preparation of tert-butyl ethers General procedure: 10 mmol of substrate, 2 g of molecular sieves and 10 mL of MTBE were taken in a 50 mL round bottom flask fitted with septum and cooled to 25 °C. To this solution 20 mmol of sulfuric acid was added very slowly using syringe. Reaction was carried out at 25 °C for given reaction time as shown in Table 4. Reaction mass was slowly quenched in to 20 mL of saturated aqueous solution of sodium bicarbonate. Organic layer was separated and washed with water (2 × 20 mL), dried over anhydrous sodium sulphate. Unreacted MTBE was recovered and reused. Obtained residue was purified by eluting through flash column using hexane and MTBE (10:1).

Reference： [1]Location in patent: experimental part Mallesha; Prahlada Rao; Suhas; Channe Gowda [Tetrahedron Letters, 2012, vol. 53, # 6, p. 641 - 645]

46
[ 905724-75-6 ]
[ 24324-17-2 ]
C₂₆H₂₁NO₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0℃; for 1h; Inert atmosphere;	2.5 EXAMPLE 2Step 55-((R)-5-hydroxy-2,3-dihydro-1H-inden-1-yl)thiazolidine-2,4-dione 2-6 was prepared according to WO 2006/083781. A mixture of 2-6 (2.00 g, 8.04 mmol), (9H-fluoren-9-yl)methanol (3.15 g, 16.1 mmol), and triphenylphosphine (6.31 g, 24.1 mmol) was dissolved in THF (60 mL) at 0° C. under N2. Diisopropyl azodicarboxylate (3.58 g, 17.7 mmol) was added to the mixture dropwise. The mixture was stirred at 0° C. for 1 h. The mixture was diluted with water (50 mL) and extracted with EtOAc. The layers were separated, and the organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography (eluting with hexanes/EtOAc 9:1 to 7:3) to provide the crude product (7.50 g) as well as a diisopropyl azodicarboxylate related impurity. The crude product was purified by prep-HPLC (XBridge ODB C18, 5 μm, 30×150 mm, 43 mL/min, acetonitrile/water 10:90 to 90:10 at 25 min, total run 50 min). The product containing fractions were combined and concentrated in vacuo to provide 2-7 (2.8 g, 82%) as a white solid (2:1 mixture of diastereomers). 1H NMR (300 MHz, CDCl3) δ 7.75 (d, J=7.4 Hz, 2H), 7.55-7.18 (m, 6H), 7.03 (d, J=7.9 Hz, 0.65H), 6.91 (d, J=8.1 Hz, 0.35H), 6.74-6.62 (m, 1.65H), 6.50 (dd, J=2.0, 8.3 Hz, 0.35H), 4.87 (d, J 3.8 Hz, 0.65H), 4.80-4.70 (m, 1H), 4.58 (d, J=3.8 Hz, 0.35H), 4.36 (t, J=7.0 Hz, 1H), 4.20-3.80 (m, 3H), 3.10-2.75 (m, 2H), 2.55-2.35 (m, 0.35H), 2.20-2.00 (m, 1H), 1.90-1.79 (m, 0.65H)

Reference： [1]Current Patent Assignee: MERCK & CO INC - US2011/312995, 2011, A1 Location in patent: Page/Page column 51

47
[ 24324-17-2 ]
[ 75-05-8 ]
[ 63839-86-1 ]

Yield	Reaction Conditions	Operation in experiment
83%	With trimethylsilyl trifluoromethanesulfonate at 20℃; for 65h;
83%	Stage #1: 9-Fluorenylmethanol; acetonitrile With trimethylsilyl trifluoromethanesulfonate at 20℃; for 65h; Stage #2: With water	General procedure (GP 1) for reactions with acetonitrile or acrylonitrile. General procedure: TMSOTf (336 mg, 1.51 mmol) is added to a solution of the alcohol (0.755 mmol) in the respective nitrile (3 mL) and the mixture is stirred at rt for 65 h. H2O (25 mL) and brine (25 mL) are added, and the mixture is extracted with EtOAc (3 × 30 mL). The combined organic layers are dried (Na2SO4) and concentrated. The crude product is purified by flash column chromatography (silica gel).

Reference： [1]Pfaff, Dominik; Nemecek, Gregor; Podlech, Joachim [Helvetica Chimica Acta, 2012, vol. 95, # 10, p. 1851 - 1856,6]
[2]Pfaff, Dominik; Nemecek, Gregor; Podlech, Joachim [Beilstein Journal of Organic Chemistry, 2013, vol. 9, p. 1572 - 1577]

48
[ 24324-17-2 ]
[ 107-13-1 ]
[ 138981-57-4 ]

Yield	Reaction Conditions	Operation in experiment
67%	Stage #1: 9-Fluorenylmethanol; acrylonitrile With trimethylsilyl trifluoromethanesulfonate at 20℃; for 65h; Stage #2: With water	General procedure (GP 1) for reactions with acetonitrile or acrylonitrile. General procedure: TMSOTf (336 mg, 1.51 mmol) is added to a solution of the alcohol (0.755 mmol) in the respective nitrile (3 mL) and the mixture is stirred at rt for 65 h. H2O (25 mL) and brine (25 mL) are added, and the mixture is extracted with EtOAc (3 × 30 mL). The combined organic layers are dried (Na2SO4) and concentrated. The crude product is purified by flash column chromatography (silica gel).
52%	With trimethylsilyl trifluoromethanesulfonate at 20℃; for 65h;

Reference： [1]Pfaff, Dominik; Nemecek, Gregor; Podlech, Joachim [Beilstein Journal of Organic Chemistry, 2013, vol. 9, p. 1572 - 1577]
[2]Pfaff, Dominik; Nemecek, Gregor; Podlech, Joachim [Helvetica Chimica Acta, 2012, vol. 95, # 10, p. 1851 - 1856,6]

49
[ 24324-17-2 ]
[ 140-29-4 ]
[ 1413134-86-7 ]

Yield	Reaction Conditions	Operation in experiment
86%	With trimethylsilyl trifluoromethanesulfonate at 20℃; for 65h;
86%	Stage #1: 9-Fluorenylmethanol; phenylacetonitrile With trimethylsilyl trifluoromethanesulfonate at 20℃; for 65h; Stage #2: With water	General procedure (GP 3) for reactions with benzyl cyanide or benzonitrile General procedure: TMSOTf (336 mg, 1.51 mmol) is added to a solution of the alcohol (0.755 mmol) in the respective nitrile (3 mL) and the mixture is stirred at rt for 65 h. H2O (25 mL) and brine (25 mL) are added, and the mixture is extracted with EtOAc (3 × 30 mL). The combined organic layers are dried (Na2SO4) and concentrated, and excess nitrile is distilled off at reduced pressure (90 °C, 0.1 mbar). The crude product is purified by flash column chromatography (silica gel).

Reference： [1]Pfaff, Dominik; Nemecek, Gregor; Podlech, Joachim [Helvetica Chimica Acta, 2012, vol. 95, # 10, p. 1851 - 1856,6]
[2]Pfaff, Dominik; Nemecek, Gregor; Podlech, Joachim [Beilstein Journal of Organic Chemistry, 2013, vol. 9, p. 1572 - 1577]

50
[ 24324-17-2 ]
[ 6976-17-6 ]
[ 104-15-4 ]
[ 1443827-27-7 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 5321 - 5334

51
[ 32315-10-9 ]
[ 24324-17-2 ]
[ 28920-43-6 ]

Yield	Reaction Conditions	Operation in experiment
98%	With tributyl-amine In toluene at 0℃;	1-5; 1-2; 2 Example 2 To 0.61 g of triphosgene, 25.49 g of toluene was added to prepare a homogeneous solution, and the resulting solution was referred to as solution A. To 1.42 g of tributylamine and 1.00 g of 9-fluorenylmethanol, 22.81 g of toluene was added to prepare a homogeneous solution, and the resulting solution was referred to as solution B. A T-shape mixer (inner diameter: 2 mm, material: polytetrafluoroethylene (PTFE)) and a retention line (inner diameter of tube: 2 mm, material: polytetrafluoroethylene (PTFE)) were placed in a constant-temperature bath at 0° C. Then, the solution A and the solution B were each transferred using a diaphragm pump (manufactured by KNF Japan Co. Ltd.) at a rate of 2 ml/min (linear velocity: 127 cm/min) and mixed by the T-shape mixer, and the resulting mixture was allowed to flow in the retention line for 4 minutes to perform a reaction. The reaction solution was quenched while stirring with 34.85 g of a 13% phosphoric acid aqueous solution in a flask. After separation, 71.85 g of an organic layer containing 1.29 g of 9-fluorenylmethyl chloroformate was obtained (yield: 98%). No crystals precipitated during the reaction, and the reaction solution was a clear solution.
	With pyridine In dichloromethane at 0 - 20℃; Inert atmosphere;
	With pyridine In dichloromethane at 0 - 20℃; Inert atmosphere;

98 %Chromat.	With tributyl-amine In toluene at 0℃; for 0.0666667h; Flow reactor;
	With pyridine In toluene at 0 - 20℃;

Reference： [1]Current Patent Assignee: KANEKA CORPORATION - US2019/177262, 2019, A1 Location in patent: Paragraph 0051-0052; 0060-0067
[2]Diosdado, Saioa; Etxabe, Julen; Izquierdo, Joseba; Landa, Aitor; Mielgo, Antonia; Olaizola, Iurre; Lopez, Rosa; Palomo, Claudio [Angewandte Chemie - International Edition, 2013, vol. 52, # 45, p. 11846 - 11851][Angew. Chem., 2013, vol. 125, # 45, p. 12062 - 12067,6]
[3]Diosdado, Saioa; Lopez, Rosa; Palomo, Claudio [Chemistry - A European Journal, 2014, vol. 20, # 21, p. 6526 - 6531]
[4]Yasukouchi, Hiroaki; Nishiyama, Akira; Mitsuda, Masaru [Organic Process Research and Development, 2018, vol. 22, # 2, p. 247 - 251]
[5]Chang, Sukbok; Jung, Hoimin; Kim, Dongwook; Lee, Jeonghyo; Lee, Jia; Park, Juhyeon [Journal of the American Chemical Society, 2020, vol. 142, # 28, p. 12324 - 12332]

52
[ 24324-17-2 ]
[ 1172579-62-2 ]

Reference： [1]Chemistry - A European Journal,2014,vol. 20,p. 6526 - 6531

53
[ 24324-17-2 ]
C₁₁H₁₇BN₂O₅ [ No CAS ]
C₂₅H₂₉BN₂O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With copper(l) chloride In N,N-dimethyl-formamide at 23℃; for 3h;	α-Boryl Carbamates 7a-e; Procedure 1C (Table 3) General procedure: In a vial equipped with a stirring bar and a screw-cap lid was dissolved the appropriate α-boryl isocyanate 2 (0.30 mmol, 1.0 equiv) in anhydrous DMF (2 mL). Alcohol (0.90 mmol, 3.0 equiv) and CuCl (0.30 mmol, 1.0 equiv) were added subsequently and the reaction mixture was stirred at r.t. for 3 h until the reaction was complete as judged by TLC (eluent: EtOAc) or crude 1H NMR analysis. The resulting green mixture was diluted with EtOAc (10 mL) and the CuCl suspension was filtered off. The filtrate was washed with H2O (2 × 3 mL) and brine (3 mL). The organic layers were concentrated to remove the solvent. The crude residue was purified by flash column chromatography on silica gel [hexanes-EtOAc (50:50) →EtOAc → EtOAc-MeCN (90:10)] to afford the pure product.

Reference： [1]Zajdlik, Adam; He, Zhi; St Denis, Jeffrey D.; Yudin, Andrei K. [Synthesis, 2014, vol. 46, # 4, p. 445 - 454]

54
[ 1033814-13-9 ]
[ 24324-17-2 ]
[ 1621325-96-9 ]

Yield	Reaction Conditions	Operation in experiment
63%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 25℃; for 2h;	Synthesis of S6: To a solution of S52 (468.7 mg, 1.31 mmol) in CH2Cl2 (35 mL) were added 9-fluorenemethanol (386.6 mg, 1.97 mmol), EDCI (504.2 mg, 2.63 mmol), and DMAP (160.0 mg, 1.31 mmol) at 25 °C. After stirring for 2 h at 25 °C, the reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (silica gel, EtOAc/hexanes = 1/3) to afford S6 (441.7 mg, 63%)
63%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 25℃; for 2h;	1 To a solution of S5 (468.7 mg, 1.31 mmol) (which was prepared as described in Bowers, A.; West, N.; Taunton, J.; Schreiber, S. L.; Bradner, J. E.; Williams, R. M. J. Am. Chem. Soc. 2008, 130, 11219) in CH2C12(35 mL) were added 9-fluorenemethanol (386.6 mg, 1.97 mmol), EDCI (504.2 mg, 2.63 mmol), and DMAP (160.0 mg, 1.31 mmol) at 25 °C. After stirring for 2 h at 25 °C, the reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (silica gel, EtOAc/hexanes = 1/3) to afford S6 (441.7 mg, 63%):]H NMR (400 MHz, CDC13) δ 7.98 (s, 1H), 7.74 (dd, J = 7.6, 4.4 Hz, 2H), 7.63 (dd, J = 7.2, 0.4 Hz, 2H), 7.38 (ddd, J = 10.4, 7.2, 7.2 Hz, 2H), 7.24 (ddd, J = 23.6, 7.6, 7.6 Hz, 2H), 5.47 (br s, 1H), 4.66 (d, J = 6.0 Hz, 2H), 4.51(d, J = 7.6 Hz, 2H), 4.27 (dd, / = 6.8, 6.8 Hz, 1H), 3.79 (d, / = 11.2 Hz, 1H), 3.24 (d, / = 11.6 Hz, 1H), 1.67 (s, 3H), 1.41 (s, 9H).

Reference： [1]Kim, Bumki; Park, Heekwang; Salvador, Lilibeth A.; Serrano, Patrick E.; Kwan, Jason C.; Zeller, Sabrina L.; Chen, Qi-Yin; Ryu, Soyoung; Liu, Yanxia; Byeon, Seongrim; Luesch, Hendrik; Hong, Jiyong [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 16, p. 3728 - 3731]
[2]Current Patent Assignee: DUKE UNIVERSITY - WO2015/200699, 2015, A2 Location in patent: Page/Page column 31-32; 34-35

55
[ 24324-17-2 ]
[ 14296-92-5 ]
C₂₆H₃₀N₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
520 mg	With dmap; dicyclohexyl-carbodiimide; In tetrahydrofuran; at 20℃;	Step a)DCC (430 mg, 2.1 mmol) was added into a solution of Boc-Gly-L-Pro dipeptide (540mg, 2.0 mmol) in 20 mis of THF at room temperature followed by 9-fluorenylmethanol (400mg, 2mmol) and 15 mg of DMAP. The reaction mixture was stirred overnight and then 20g of silica gel was added and the mixture was stripped to dryness. The residue was loaded into an empty sample-cartridge (ISCO) and the product was washed out gradually by increasing the ethyl acetate gradient in hexanes to provide 520 mg product .1 H NM R (300 MHz, CDCI3) delta ppm 7.78 (d, J7.5Hz, 2H), 7.55(d, J=7.2Hz, 2H), 7.40(t, J=7.5Hz, 2H), 7.31 (t, J=5.7Hz, 2H), 4.71 (m, 2H) 4.55 (ddd, J1 =3Hz, J2=6Hz, J3=20Hz, 1 H) 4.23 (t, J=5.4Hz, 1 H) 4.48 (dd, J=3Hz, 1 H), 3.90 (dd, J 1 =5.4Hz, J2=17Hz, 1 H), 3.60(dd, J1 =4.0Hz, J2=1 7Hz), 2.02 (2H, m), 3.26 (1 H, m), 1 .72 (m, 1 OH), 1 .47(1 H, b)

Reference： [1]Patent: WO2015/164289,2015,A1 .Location in patent: Page/Page column 68

56
[ 24324-17-2 ]
[ 79-08-3 ]
[ 857722-29-3 ]

Yield	Reaction Conditions	Operation in experiment
87%	With dicyclohexyl-carbodiimide; 4-(dimethylamino)pyridinium tosylate In dichloromethane at 0℃; for 1h;	14.a 9-Fluorenylmethyl bromoacetate Under ice-cooling, 9-fluorenemethanol (99%, 0.694 g, 3.5 mmol), bromoacetic acid (99%, 0.406 g, 2.9 mmol), DPTS (0.130 g, 0.44 mmol) and DCC (99%, 0.729 g, 3.5 mmol) were combined in dichloromethane (9 mL), stirred at 0° C. for 1 h, and the precipitate of dicyclohexylurea was filtered off from the cold mixture. The filtrate was diluted with cold ethyl acetate (30 mL), washed twice with cold 5% aqueous solution of NaH2PO4 (60 mL, acidified with H3PO4 to pH=3), freed of water droplets, and the solvents were distilled off in vacuo. The residue was extracted with cold pentane to remove the excess of DCC, and purified by flash chromatography (silica-gel, hexane-CHCl3, 5:1 to 1:1) followed by crystallization from cold hexane. Yield of 8: 0.795 g (87%). The purity was confirmed by TLC (SiO2, heptane-ethyl acetate, 9:1).

Reference： [1]Current Patent Assignee: THE CHILDREN'S HOSPITAL OF PHILADELPHIA - US9233163, 2016, B2 Location in patent: Page/Page column 25

57
[ 24324-17-2 ]
[ 598-21-0 ]
bromoacetic acid Fm ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39.8%	With triethylamine In dichloromethane at 20℃; for 1h; Cooling with ice;	41 Synthesis of Bromoacetic Acid Fm Ester (102) Synthesis of Bromoacetic Acid Fm Ester (102): 9-Fluorenyl methanol (10 g, 1 eq) was dissolved in 100 mL of dichlormethane, and triethylamine (6.14 g, 1.19 eq) was added. The reaction mixture was cooled in ice bath, and a solution of bromoacetyl bromide (10.3 g, 1 eq) in 10 mL methylene chloride was added under stirring over 1 h. The cloudy mixture was warmed to room temperature, and stirred overnight. The mixture was washed with water (100 mL x 3) and brine. Thecombined organic phase was dried and concentrated under reduced pressure. The crude product thus obtained was purified via silica gel chromatography (PE:EA = 300:1-50:1) giving 6.4 g product 102 as a light yellow solid in 39.8% yield.

Reference： [1]Current Patent Assignee: MODERNA THERAPEUTICS INC - WO2015/196130, 2015, A2 Location in patent: Page/Page column 608

58
[ 40052-13-9 ]
[ 24324-17-2 ]
tert-butyl fluorenylmethyl malonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 10 - 35℃; for 24h;	[COMPARATIVE EXAMPLE 19] (Synthesis Process R): Preparation of des(1-7)-Dibenzylaminocarbamoylacetyl-[Arg(Me)9,Trp10]MS10 (Compound No. 434) Dibenzylaminocarbamoylacetyl-Leu-Arg(Me)-Trp-NH2 After 1.54 mL of <strong>[40052-13-9]mono-tert-butyl malonate</strong>, 1.08 g of fluorenylmethanol and 61 mg of DMAP were dissolved in 20 mL of DCM 20, 1.15 g of WSCD HCl was added to the solution, followed by stirring at room temperature for 24 hours. The solvent was distilled off in vacuum, the residue was dissolved in AcOEt. The solution was then washed with 1N HCl aq. solution, satd. NaHCO aq. solution and then satd. NaCl aq. solution. After drying over NaSO, the solvent was concentrated and the concentrate was purified by flush column chromatography to give 1.62 g (yield 96%) of tert-butyl fluorenylmethyl malonate. In 20 mL of TFA, 61 mg of tert-butyl fluorenylmethyl malonate was dissolved and the solution was stirred at room temperature for 2 hours. After the solvent was distilled off in vacuum, the residue was dissolved in AcOEt, followed by washing with satd. NaCl aq. solution. After drying over NaSO, the solvent was concentrated and purified by flush column chromatography to give 850 mg (yield 67%) of mono-fluorenylmethyl malonate. After 5 mL of 20% piperidine/DMF was added to 46 mg (15 mumol) of Fmoc-LeuArg(Me,Boc)Trp(Boc)-Rink amide MBHA resin prepared in a manner similar to COMPARATIVE EXAMPLE 15, the solution was shaken at room temperature for 30 minutes. After the resin washed, 42 mg of mono-fluorenylmethyl malonate, 70 mg of PyBrop, 300 muL of 0.5M HOAt/DMF, 52 muL of DIEA and 1 mL of DMF were added to the resin, and the mixture was shaken for 15 hours. After this procedure was repeated twice, 8 muL of AcO, 5 muL of DIEA and 2 mL of DCM were added, followed by stirring at room temperature for 30 minutes. After the resin washed and then dried, 5 mL of 20% piperidine/DMF was added to a half of the resin, followed by stirring at room temperature for 30 minutes. After the resin washed, 13 mg of dibenzylhydrazine, 28 mg of PyBrop, 120 muL of 0.5M HOAt/DMF, 21 muL of DIEA and 1 mL of DMF were added to the resin, followed by shaking for 15 hours. After the resin washed and then dried, 200 muL of TFA/PhSMe/m-cresol/TIS/EDT (85/5/5/2.5/2.5) was added to the resin, followed by stirring for 2 hours. Ether was added to the reaction solution, the resulting precipitate was centrifuged and the supernatant was removed. This procedure was repeated for washing. The residue was extracted with an aqueous acetic acid solution and the extract was filtered to remove the resin. Then, linear density gradient elution (120 minutes) was performed with eluants A/B: 83/17-63/37 using: 0.1% TFA in water and eluant B: 0.1% TFA-containing acetonitrile on preparative HPLC using YMC D-ODS-5-ST S-5 120A column (20 x 150 mm). The fractions containing the product were collected and lyophilized to give 21.6 mg of white powders. Mass spectrum (M+H)+ 767.6 (Calcd. 767.4) Elution time on HPLC: 14.5 min Elution conditions: Column: Wakosil-II 5C18 HG (4.6 x 100 mm) Eluant: linear density gradient elution with eluants A/B = 100/0-30/70, using 0.1% TFA in water as eluant A and acetonitrile containing 0.1% TFA (25 mins.) Flow rate: 1.0 ml/min.

Reference： [1]Patent: EP2113513,2016,B1 .Location in patent: Paragraph 0262

59
[ 843666-40-0 ]
[ 24324-17-2 ]
tert-butyl 17-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)heptadecanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
16.94%	With diphenyl phosphoryl azide; triethylamine; In toluene; at 20℃;Reflux;	Diphenyl phosphorazidate (1.738 ml, 8.04 mmol) was added to a solution of 1 8-(tert-butoxy)- 1 8-oxooctadecanoic acid (1.49 g, 4.02 mmol) and triethylamine (1.115 ml, 8.04 mmol) in Toluene (16.08 ml) at room temperature. The resulting mixture was heated under reflux overnight. The reaction mixture was cooled to roomtemperature and quenched with a 5% citric acid solution. The mixture was concentrated to half volume in vacuo and then extracted 3 times with dichloromethane. The combined organics were washed with brine, dried over MgSO4, filtered, and concentrated to give crude product. The crude product was dissolved in dichloromethane and applied to a 40 g ISCO silica gel cartridge. Theproduct was eluted by a 0-25% ethyl acetate/hexanes gradient. Like fractions were combined and concentrated to give tert-butyl 1 7-((((9H-fluoren-9- yl)methoxy)carbonyl)amino)heptadecanoate (0.384 g, 0.68 1 mmol, 16.94 % yield) as a white solid. ?H NMR (400MHz, CHLOROFORM-d) oe 7.78 (d, J7.3 Hz, 2H),7.61 (d, J7.5 Hz, 2H), 7.41 (t, J7.4 Hz, 2H), 7.33 (td, J=7.4, 1.0 Hz, 2H), 4.41 (d,J7.0 Hz, 2H), 4.24 (d, J=6.8 Hz, 1H), 3.20 (q, J=6.8 Hz, 2H), 2.21 (t, J=7.5 Hz, 2H),1.61 - 1.48 (m, 4H), 1.45 (s, 9H), 1.26 (s, 24H).

Reference： [1]Patent: WO2016/77518,2016,A1 .Location in patent: Page/Page column 289; 290

60
[ 24324-17-2 ]
[ 7693-46-1 ]
[ 67827-10-5 ]

Yield	Reaction Conditions	Operation in experiment
81%	Stage #1: 9-Fluorenylmethanol With pyridine In dichloromethane at 0℃; for 0.166667h; Stage #2: 4-Nitrophenyl chloroformate In dichloromethane at 20℃; for 1.5h;	General procedure for the synthesis of p-nitrophenyl carbonate derivatives General procedure: The alcohol (0.5 g) was dissolved in dry DCM (6 mL) and cooled to 0 C in an ice bath. Dry pyridine (2 equiv) was added and the mixture was allowed to stir for 10 min. p-Nitrophenyl chloroformate (1.2 equiv) dissolved in DCM (2 mL) was added stirring continued for 1.5 h at room temperature. After completion, the reaction mixture was extracted with DCM (2 × 30 mL), the organic layer washed with water, brine and dried over anhydrous Na2SO4. The solvent was evaporated and the crude compound was purified by column chromatography using hexane/ethylacetate.

Reference： [1]Vangala, Madhuri; Shinde, Ganesh P. [Beilstein Journal of Organic Chemistry, 2016, vol. 12, p. 2086 - 2092]

61
[ 24324-17-2 ]
[ 598-21-0 ]
9H-fluoren-9-yl 2-bromoacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39.8%	With triethylamine In dichloromethane at 20℃; for 1h; Cooling with ice;	41 Synthesis of Bromoacetic Acid Fm Ester (102) Synthesis of Bromoacetic Acid Fm Ester (102): 9-Fluorenyl methanol (10 g, 1 eq) was dissolved in 100 mL of dichlormethane, and triethylamine (6.14 g, 1.19 eq) was added. The reaction mixture was cooled in ice bath, and a solution of bromoacetyl bromide (10.3 g, 1 eq) in 10 mL methylene chloride was added under stirring over 1 h. The cloudy mixture was warmed to room temperature, and stirred overnight. The mixture was washed with water (100 mL x 3) and brine. The combined organic phase was dried and concentrated under reduced pressure. The crude product thus obtained was purified via silica gel chromatography (PE:EA = 300:1-50:1) giving 6.4 g product 102 as a light yellow solid in 39.8% yield.

Reference： [1]Current Patent Assignee: MODERNA THERAPEUTICS INC - EP2918275, 2015, A1 Location in patent: Paragraph 2122; 2123

62
[ 18951-85-4 ]
[ 24324-17-2 ]
C₂₄H₂₉NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	Stage #1: (R)-citronellic acid With triethylamine In toluene at 20℃; for 0.5h; Stage #2: With diphenyl phosphoryl azide In toluene at 80℃; for 1h; Stage #3: 9-Fluorenylmethanol In toluene at 120℃; for 1h;	2.1 In the first step Compound 34 (947 mg, 5.56 mmol) was dissolved in toluene(8 ml), and triethylamine(0.848 ml, 6.12 mmol)And the mixture was stirred at room temperature for 30 minutes. Diphenylphosphonoazide(1.32 ml, 6.12 mmol), and the mixture was stirred at 80 ° C. for 1 hour, (9H-fluoren-9-yl) methanol(5.46 g, 27.8 mmol)And the mixture was refluxed under heating at 120 ° C. for 1 hour. After cooling to room temperature,The reaction was stopped by adding saturated aqueous sodium hydrogen carbonate solution.The reaction solution was extracted with ethyl acetate, and the organic layer was washed with saturated brine.After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure.The obtained residue was purified by silica gel column chromatography(Ethyl acetate-hexane) to give Compound 35(1.5 g, yield 74%).

Reference： [1]Current Patent Assignee: SHIONOGI & CO., LTD. - JP6267397, 2018, B1 Location in patent: Paragraph 0079

63
[ 24324-17-2 ]
[ 4651-67-6 ]
C₃₈H₄₈O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97.1%	With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 0℃; for 16h;	3alpha-Hydroxy-7-oxo-5beta-cholanoic acid (39.0 g, 100 mmol),Fluorenyl methanol (21.6g, 110mmol),2gDMAP (4-dimethylaminopyridine)Soluble in 200ml methylene chlorideStir and cool to 0C.DCC (dicyclohexylcarbodiimide) (24.7 g, 120 mmol) was slowly added dropwise50ml of methylene chloride solution was added dropwise.Stir and stir for 16 hours.Filter, concentrate the filtrate3[alpha]-Hydroxy-7-oxo-5[beta]-benzalkanoic acid methyl ester (53.9 g, yield 97.1%).

Reference： [1]Patent: CN107383139,2017,A .Location in patent: Paragraph 0062

64
[ 24324-17-2 ]
[ 4651-67-6 ]
C₃₉H₅₀O₄ [ No CAS ]

Reference： [1]Patent: CN107383139,2017,A

65
[ 57294-38-9 ]
[ 24324-17-2 ]
fluorenylmethyl N^γ-(t-butyloxycarbonyl)aminobutyric acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	Stage #1: N-(tert-butoxycarbonyl)-4-aminobutanoic acid With 1,1'-carbonyldiimidazole In dichloromethane at 20℃; for 1h; Inert atmosphere; Stage #2: 9-Fluorenylmethanol In dichloromethane at 20℃; for 4h; Inert atmosphere;	Synthesis of fluorenylmethyl A^-f-butyloxycarbonyl-aminobutyric Acid (Boc-GABA-Fm) [70] Boc-GAB A (1.0 g, 9.8 mmol) was pre-activated with CDI (1.6 g, 9.8 mmol) in 2 mL of anhydrous DCM at room temperature under nitrogen atmosphere for 1 h. Fluorenylmethanol (1.3 g, 6.5 mmol) was added and the reaction carried out at room temperature under nitrogen atmosphere for 4h. The mixture was diluted to 20 mL with DCM, washed sequentially with 20 mL 5% NaHCCb, brine and dried over sodium sulfate. After removing DCM under reduced pressure, the product was collected as an off-white solid in 95% yield (1.2 g). Removal of the Boc-protecting group was carried out with 50% TFA/DCM at room temperature in 30 min. All solvents were removed under a gentle nitrogen stream; the crude product obtained after repeated 20-mL hexane washes (5X) was ready to be used for the next step. [71] NMR (CDCh, 400 MHz): δ 7.80 (d, 2H, J = 8.0 Hz), 7.61 (d, 2H, J = 7.4 Hz), 7.44 (t, 2H, J = 7.3 Hz), 7.35 (t, 2H, J = 7.9 Hz), 4.56 (s, 1H), 4.45 (d, 2H, J = 6.7 Hz), 4.24 (t, 1H, J = 7.3 Hz), 3.13 (m, 2H), 2.43 (t, 2H, J = 7.3 Hz), 1.81 (q, 2H, J = 6.8 Hz), 1.46 (s, 9H); 13C NMR (CDCh, 100 MHz): δ 143.8, 141.3, 127.8, 127.1, 125.0, 120.0, 66.2, 46.9, 38.4, 31.5, 28.4, 25.3, MS (ESI+): m/z (intensity), 381.7 ([M+H]+, 10%), 282.0 ([M+H-Boc], 100%).
95%	Stage #1: N-(tert-butoxycarbonyl)-4-aminobutanoic acid With 1,1'-carbonyldiimidazole In dichloromethane at 20℃; for 1h; Inert atmosphere; Stage #2: 9-Fluorenylmethanol In dichloromethane at 20℃; for 4h; Inert atmosphere;	(9H-Fluoren-9-yl)methyl 4-((tert-butoxycarbonyl)amino)butanoate (Boc-GABA-Fm) Boc-GABA (1.0 g, 9.8 mmol) was pre-activated with CDI(1.6 g, 9.8 mmol) in 2 mL of anhydrous DCM at roomtemperature under nitrogen atmosphere for 1 h. Fluorenylmethanol(1.3 g, 6.5 mmol) was added and the reactioncarried out at room temperature under nitrogen atmospherefor 4 h. The mixture was diluted to 20 mL with DCM,washed sequentially with 20 mL 5% NaHCO3, brine anddried over sodium sulfate. After removing DCM underreduced pressure, the product was collected as an off-whitesolid in 95% yield (1.2 g). Removal of the Boc-protecting group was carried out with 50% TFA/DCM at room temperaturein 30 min. All solvents were removed under agentle nitrogen stream to afford the intermediate Boc-GABA-Fm, which was washed repeatedly with hexanes(5 × 20 mL) and used for the next step.

Reference： [1]Current Patent Assignee: RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY - WO2018/144880, 2018, A1 Location in patent: Paragraph 70-71
[2]Aloysius, Herve; Hu, Longqin [Medicinal Chemistry Research, 2020]

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[ 88744-04-1 ]
[ 67-56-1 ]
[ 771-61-9 ]
[ 24324-17-2 ]