Name: 157911-56-3|1-(Bromomethyl)-2,4,5-trifluorobenzene|97%
Brand: Ambeed
SKU: A310038
Price: 7.0 USD
Availability: InStock
Rating: 96 (32 reviews)

1
[ 1068-90-2 ]
[ 157911-56-3 ]
[ 324027-92-1 ]

Yield	Reaction Conditions	Operation in experiment
84%	Stage #1: 2-acetylaminomalonic acid diethyl ester With sodium ethanolate In ethanol at 20℃; for 0.166667h; Stage #2: 2,4,5-trifluorobenzyl bromide In ethanol for 6h; Reflux;
	With ethanol; sodium for 2h; Heating;

Reference： [1]Parmeggiani, Fabio; Rué Casamajo, Arnau; Colombo, Danilo; Ghezzi, Maria Chiara; Galman, James L.; Chica, Roberto A.; Brenna, Elisabetta; Turner, Nicholas J. [Green Chemistry, 2019, vol. 21, # 16, p. 4368 - 4379]
[2]Matsushima; Fujita; Okada; Shirasu; Nose; Shimohigashi [Bulletin of the Chemical Society of Japan, 2000, vol. 73, # 11, p. 2531 - 2538]

2
[ 157911-56-3 ]
[ 485-71-2 ]
(1S,2S,4S,5R)-2-((R)-Hydroxy-quinolin-4-yl-methyl)-1-(2,4,5-trifluoro-benzyl)-5-vinyl-1-azonia-bicyclo[2.2.2]octane; bromide [ No CAS ]

Reference： [1]Organic letters,2002,vol. 4,p. 4245 - 4248

3
[ 78342-42-4 ]
[ 157911-56-3 ]
[ 486460-07-5 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: (S)-2-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine With n-butyllithium In tetrahydrofuran at -78℃; Stage #2: 2,4,5-trifluorobenzyl bromide In tetrahydrofuran at -78℃;
	With n-butyllithium In tetrahydrofuran; hexanes at -70℃; for 3h;	3.A To a solution of 3,42 g (18.5 mmol) of commercially available (2S)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine in 100 mL of tetrahydrofuran at -70 °C was added 12 mL (19 mmol) of a1.6M solution of butyllithium in hexanes. After stirring at this temperature for 20 min, 5 g (22.3 mmol)of 2,4,5-trifluorobenzyl bromide in 20 mL of tetrahydrofuran was added and stirring was continued for 3h before warming the reaction to ambient temperature. The reaction was quenched with water,concentrated in vacuo, and extracted with ethyl acetate. The combined organic phase was washed with brine, dried, and concentrated in vacuo. Purification by flash chromatography (silica gel, 0-5% ethylacetate in hexanes) afforded the title compound.IHNMR (500 MHz, CDCls): 8 7.01 (m, 1H), 6.85 (m, 1H), 4.22 (m, 1H), 3.78 (m, 3H), 3.64 (m, 3H),3.61 (m, 1H), 3.20 (m, 1H), 2.98 (m, 1H), 2.20 (m, 1H), 0.99 (d, 3H, J = 8 Hz), 0.62 (d, 3H, J = 8 Hz).

Reference： [1]Kim, Dooseop; Wang, Liping; Beconi, Maria; Eiermann, George J.; Fisher, Michael H.; He, Huaibing; Hickey, Gerard J.; Kowalchick, Jennifer E.; Leiting, Barbara; Lyons, Kathryn; Marsilio, Frank; McCann, Margaret E.; Patel, Reshma A.; Petrov, Aleksandr; Scapin, Giovanna; Patel, Sangita B.; Roy, Ranabir Sinha; Wu, Joseph K.; Wyvratt, Matthew J.; Zhang, Bei B.; Zhu, Lan; Thornberry, Nancy A.; Weber, Ann E. [Journal of Medicinal Chemistry, 2005, vol. 48, # 1, p. 141 - 151]
[2]Current Patent Assignee: MERCK & CO INC - WO2006/23750, 2006, A2 Location in patent: Page/Page column 42-43

4
[ 157911-56-3 ]
[ 337307-10-5 ]
[ 391888-88-3 ]

Yield	Reaction Conditions	Operation in experiment
70%	With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃;
9.37 g (46%)	With NaH; ammonium chloride In ethyl acetate; N,N-dimethyl-formamide	1.B B B (2S,4R)-2-(2,4,5-Trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidine-1-carboxylic Acid Tert-butyl Ester A solution of 15.5 g (32.59 mmol) (2S,4R)-2-Hydroxymethyl-4-tritylsulfanyl-pyrrolidine-1-carboxylic acid tert-butyl ester and 24.7 g (109.77 mmol) 2,4,5-trifluoro-benzylbromide in 700 ml DMF at 0° C. was treated with 2.28 g (52.14 mmol) of 55% NaH in 4 portions and warmed up to RT during 7 h. The reaction was cooled to 0° C. and treated with 500 ml aqueous saturated NH4Cl solution, extracted with EtOAc (3x). The organic phase was washed with 10% NaCl dried over Na2SO4 and evaporated. Flash column chromatography on silica gel with hexane/EtOAc (9:1 to 8.5:1.5) gave 9.37 g (46%) of (2S,4R)-2-(2,4,5-Trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidine-1-carboxylic acid tert-butyl ester, MS: 620 (MH+).

Reference： [1]Berger, Yann; Dehmlow, Henrietta; Blum-Kaelin, Denise; Kitas, Eric A.; Löffler, Bernd-Michael; Aebi, Johannes D.; Juillerat-Jeanneret, Lucienne [Journal of Medicinal Chemistry, 2005, vol. 48, # 2, p. 483 - 498]
[2]Current Patent Assignee: ROCHE HOLDING AG - US2002/55632, 2002, A1

5
(R)-N-tert-butoxycarbonyl serine [ No CAS ]
[ 157911-56-3 ]
[ 616881-95-9 ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium hydride In N,N-dimethyl-formamide at 20℃;

Reference： [1]Evers, Britta; Ruehter, Gerd; Berg, Martina; Dodge, Jeffrey A.; Hankotius, Dirk; Hary, Ulrike; Jungheim, Louis N.; Mest, Hans-Juergen; De La Nava, Eva-Maria Martin; Mohr, Michael; Muehl, Brian S.; Petersen, Soenke; Sommer, Birgit; Riedel-Herold, Grit; Tebbe, Mark J.; Thrasher, Kenneth J.; Voelkers, Silke [Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 24, p. 6748 - 6762]

6
[ 157911-56-3 ]
[ 486460-00-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: n-BuLi / tetrahydrofuran / -78 °C 1.2: tetrahydrofuran / -78 °C 2.1: aq. HCl / acetonitrile / 72 h / 20 °C 2.2: 2.41 g / triethylamine / CH₂Cl₂ / 16 h / 20 °C 3.1: aq. LiOH / tetrahydrofuran / 20 °C 4.1: isobutyl chloroformate; triethylamine / diethyl ether / 0.25 h / -20 °C 4.2: 0.36 g / diethyl ether / 1 h 5.1: 401 mg / aq. silver benzoate / dioxane / 2 h / 20 °C / sonication
	Multi-step reaction with 4 steps 1.1: magnesium / diethyl ether / Inert atmosphere 1.2: 3 h / 0 - 20 °C / Inert atmosphere 2.1: chloro(1,5-cyclooctadiene)rhodium(I) dimer; pyridinium p-toluenesulfonate; (2S)-1-[(1S)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(diphenylphosphino)ferrocene; Benzophenone imine / 1,2-dichloro-ethane / 36 h / 80 °C / Schlenk technique; Inert atmosphere; Sealed tube 2.2: 12 h / 20 °C / Schlenk technique; Inert atmosphere; Sealed tube 3.1: dichloro bis(acetonitrile) palladium(II); p-benzoquinone / <i>tert</i>-butyl alcohol / 18 h / 20 °C / Inert atmosphere 4.1: sodium dihydrogenphosphate; sodium chlorite; water; 2-methyl-but-2-ene / <i>tert</i>-butyl alcohol; tetrahydrofuran / 2 h / 20 °C / Inert atmosphere

Reference： [1]Kim, Dooseop; Wang, Liping; Beconi, Maria; Eiermann, George J.; Fisher, Michael H.; He, Huaibing; Hickey, Gerard J.; Kowalchick, Jennifer E.; Leiting, Barbara; Lyons, Kathryn; Marsilio, Frank; McCann, Margaret E.; Patel, Reshma A.; Petrov, Aleksandr; Scapin, Giovanna; Patel, Sangita B.; Roy, Ranabir Sinha; Wu, Joseph K.; Wyvratt, Matthew J.; Zhang, Bei B.; Zhu, Lan; Thornberry, Nancy A.; Weber, Ann E. [Journal of Medicinal Chemistry, 2005, vol. 48, # 1, p. 141 - 151]
[2]Berthold, Dino; Breit, Bernhard [European Journal of Organic Chemistry, 2021, vol. 2021, # 46, p. 6247 - 6249]

7
[ 157911-56-3 ]
[ 486460-08-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: n-BuLi / tetrahydrofuran / -78 °C 1.2: tetrahydrofuran / -78 °C 2.1: aq. HCl / acetonitrile / 72 h / 20 °C 2.2: 2.41 g / triethylamine / CH₂Cl₂ / 16 h / 20 °C

Reference： [1]Kim, Dooseop; Wang, Liping; Beconi, Maria; Eiermann, George J.; Fisher, Michael H.; He, Huaibing; Hickey, Gerard J.; Kowalchick, Jennifer E.; Leiting, Barbara; Lyons, Kathryn; Marsilio, Frank; McCann, Margaret E.; Patel, Reshma A.; Petrov, Aleksandr; Scapin, Giovanna; Patel, Sangita B.; Roy, Ranabir Sinha; Wu, Joseph K.; Wyvratt, Matthew J.; Zhang, Bei B.; Zhu, Lan; Thornberry, Nancy A.; Weber, Ann E. [Journal of Medicinal Chemistry, 2005, vol. 48, # 1, p. 141 - 151]

8
[ 157911-56-3 ]
[ 486460-25-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: n-BuLi / tetrahydrofuran / -78 °C 1.2: tetrahydrofuran / -78 °C 2.1: aq. HCl / acetonitrile / 72 h / 20 °C 2.2: 2.41 g / triethylamine / CH₂Cl₂ / 16 h / 20 °C 3.1: aq. LiOH / tetrahydrofuran / 20 °C 4.1: isobutyl chloroformate; triethylamine / diethyl ether / 0.25 h / -20 °C 4.2: 0.36 g / diethyl ether / 1 h

Reference： [1]Kim, Dooseop; Wang, Liping; Beconi, Maria; Eiermann, George J.; Fisher, Michael H.; He, Huaibing; Hickey, Gerard J.; Kowalchick, Jennifer E.; Leiting, Barbara; Lyons, Kathryn; Marsilio, Frank; McCann, Margaret E.; Patel, Reshma A.; Petrov, Aleksandr; Scapin, Giovanna; Patel, Sangita B.; Roy, Ranabir Sinha; Wu, Joseph K.; Wyvratt, Matthew J.; Zhang, Bei B.; Zhu, Lan; Thornberry, Nancy A.; Weber, Ann E. [Journal of Medicinal Chemistry, 2005, vol. 48, # 1, p. 141 - 151]

9
[ 157911-56-3 ]
[ 486460-09-7 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 141 - 151

10
[ 157911-56-3 ]
[ 486460-32-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: n-BuLi / tetrahydrofuran / -78 °C 1.2: tetrahydrofuran / -78 °C 2.1: aq. HCl / acetonitrile / 72 h / 20 °C 2.2: 2.41 g / triethylamine / CH₂Cl₂ / 16 h / 20 °C 3.1: aq. LiOH / tetrahydrofuran / 20 °C 4.1: isobutyl chloroformate; triethylamine / diethyl ether / 0.25 h / -20 °C 4.2: 0.36 g / diethyl ether / 1 h 5.1: 401 mg / aq. silver benzoate / dioxane / 2 h / 20 °C / sonication 6.1: 71 percent / HOBT; EDC / dimethylformamide / 16 h / 20 °C 7.1: 83 percent / HCl / methanol / 1 h / 20 °C

Reference： [1]Kim, Dooseop; Wang, Liping; Beconi, Maria; Eiermann, George J.; Fisher, Michael H.; He, Huaibing; Hickey, Gerard J.; Kowalchick, Jennifer E.; Leiting, Barbara; Lyons, Kathryn; Marsilio, Frank; McCann, Margaret E.; Patel, Reshma A.; Petrov, Aleksandr; Scapin, Giovanna; Patel, Sangita B.; Roy, Ranabir Sinha; Wu, Joseph K.; Wyvratt, Matthew J.; Zhang, Bei B.; Zhu, Lan; Thornberry, Nancy A.; Weber, Ann E. [Journal of Medicinal Chemistry, 2005, vol. 48, # 1, p. 141 - 151]

11
[ 157911-56-3 ]
[ 1025950-29-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: n-BuLi / tetrahydrofuran / -78 °C 1.2: tetrahydrofuran / -78 °C 2.1: aq. HCl / acetonitrile / 72 h / 20 °C 2.2: 2.41 g / triethylamine / CH₂Cl₂ / 16 h / 20 °C 3.1: aq. LiOH / tetrahydrofuran / 20 °C 4.1: isobutyl chloroformate; triethylamine / diethyl ether / 0.25 h / -20 °C 4.2: 0.36 g / diethyl ether / 1 h 5.1: 401 mg / aq. silver benzoate / dioxane / 2 h / 20 °C / sonication 6.1: HOBT; EDC; DIPEA / dimethylformamide / 20 °C

Reference： [1]Kim, Dooseop; Wang, Liping; Beconi, Maria; Eiermann, George J.; Fisher, Michael H.; He, Huaibing; Hickey, Gerard J.; Kowalchick, Jennifer E.; Leiting, Barbara; Lyons, Kathryn; Marsilio, Frank; McCann, Margaret E.; Patel, Reshma A.; Petrov, Aleksandr; Scapin, Giovanna; Patel, Sangita B.; Roy, Ranabir Sinha; Wu, Joseph K.; Wyvratt, Matthew J.; Zhang, Bei B.; Zhu, Lan; Thornberry, Nancy A.; Weber, Ann E. [Journal of Medicinal Chemistry, 2005, vol. 48, # 1, p. 141 - 151]

12
[ 157911-56-3 ]
[ 486460-23-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: n-BuLi / tetrahydrofuran / -78 °C 1.2: tetrahydrofuran / -78 °C 2.1: aq. HCl / acetonitrile / 72 h / 20 °C 2.2: 2.41 g / triethylamine / CH₂Cl₂ / 16 h / 20 °C 3.1: aq. LiOH / tetrahydrofuran / 20 °C 4.1: isobutyl chloroformate; triethylamine / diethyl ether / 0.25 h / -20 °C 4.2: 0.36 g / diethyl ether / 1 h 5.1: 401 mg / aq. silver benzoate / dioxane / 2 h / 20 °C / sonication 6.1: 71 percent / HOBT; EDC / dimethylformamide / 16 h / 20 °C

Reference： [1]Kim, Dooseop; Wang, Liping; Beconi, Maria; Eiermann, George J.; Fisher, Michael H.; He, Huaibing; Hickey, Gerard J.; Kowalchick, Jennifer E.; Leiting, Barbara; Lyons, Kathryn; Marsilio, Frank; McCann, Margaret E.; Patel, Reshma A.; Petrov, Aleksandr; Scapin, Giovanna; Patel, Sangita B.; Roy, Ranabir Sinha; Wu, Joseph K.; Wyvratt, Matthew J.; Zhang, Bei B.; Zhu, Lan; Thornberry, Nancy A.; Weber, Ann E. [Journal of Medicinal Chemistry, 2005, vol. 48, # 1, p. 141 - 151]

13
[ 157911-56-3 ]
7-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyrazine dihydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: n-BuLi / tetrahydrofuran / -78 °C 1.2: tetrahydrofuran / -78 °C 2.1: aq. HCl / acetonitrile / 72 h / 20 °C 2.2: 2.41 g / triethylamine / CH₂Cl₂ / 16 h / 20 °C 3.1: aq. LiOH / tetrahydrofuran / 20 °C 4.1: isobutyl chloroformate; triethylamine / diethyl ether / 0.25 h / -20 °C 4.2: 0.36 g / diethyl ether / 1 h 5.1: 401 mg / aq. silver benzoate / dioxane / 2 h / 20 °C / sonication 6.1: HOBT; EDC; DIPEA / dimethylformamide / 20 °C 7.1: HCl / methanol / 20 °C

Reference： [1]Kim, Dooseop; Wang, Liping; Beconi, Maria; Eiermann, George J.; Fisher, Michael H.; He, Huaibing; Hickey, Gerard J.; Kowalchick, Jennifer E.; Leiting, Barbara; Lyons, Kathryn; Marsilio, Frank; McCann, Margaret E.; Patel, Reshma A.; Petrov, Aleksandr; Scapin, Giovanna; Patel, Sangita B.; Roy, Ranabir Sinha; Wu, Joseph K.; Wyvratt, Matthew J.; Zhang, Bei B.; Zhu, Lan; Thornberry, Nancy A.; Weber, Ann E. [Journal of Medicinal Chemistry, 2005, vol. 48, # 1, p. 141 - 151]

14
[ 157911-56-3 ]
[ 1025933-74-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: n-BuLi / tetrahydrofuran / -78 °C 1.2: tetrahydrofuran / -78 °C 2.1: aq. HCl / acetonitrile / 72 h / 20 °C 2.2: 2.41 g / triethylamine / CH₂Cl₂ / 16 h / 20 °C 3.1: aq. LiOH / tetrahydrofuran / 20 °C 4.1: isobutyl chloroformate; triethylamine / diethyl ether / 0.25 h / -20 °C 4.2: 0.36 g / diethyl ether / 1 h 5.1: 401 mg / aq. silver benzoate / dioxane / 2 h / 20 °C / sonication 6.1: HOBT; EDC; DIPEA / dimethylformamide / 20 °C

Reference： [1]Kim, Dooseop; Wang, Liping; Beconi, Maria; Eiermann, George J.; Fisher, Michael H.; He, Huaibing; Hickey, Gerard J.; Kowalchick, Jennifer E.; Leiting, Barbara; Lyons, Kathryn; Marsilio, Frank; McCann, Margaret E.; Patel, Reshma A.; Petrov, Aleksandr; Scapin, Giovanna; Patel, Sangita B.; Roy, Ranabir Sinha; Wu, Joseph K.; Wyvratt, Matthew J.; Zhang, Bei B.; Zhu, Lan; Thornberry, Nancy A.; Weber, Ann E. [Journal of Medicinal Chemistry, 2005, vol. 48, # 1, p. 141 - 151]

15
[ 157911-56-3 ]
Sitagliptin hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: n-BuLi / tetrahydrofuran / -78 °C 1.2: tetrahydrofuran / -78 °C 2.1: aq. HCl / acetonitrile / 72 h / 20 °C 2.2: 2.41 g / triethylamine / CH₂Cl₂ / 16 h / 20 °C 3.1: aq. LiOH / tetrahydrofuran / 20 °C 4.1: isobutyl chloroformate; triethylamine / diethyl ether / 0.25 h / -20 °C 4.2: 0.36 g / diethyl ether / 1 h 5.1: 401 mg / aq. silver benzoate / dioxane / 2 h / 20 °C / sonication 6.1: 71 percent / HOBT; EDC / dimethylformamide / 16 h / 20 °C 7.1: HCl / methanol / 1 h / 20 °C

Reference： [1]Kim, Dooseop; Wang, Liping; Beconi, Maria; Eiermann, George J.; Fisher, Michael H.; He, Huaibing; Hickey, Gerard J.; Kowalchick, Jennifer E.; Leiting, Barbara; Lyons, Kathryn; Marsilio, Frank; McCann, Margaret E.; Patel, Reshma A.; Petrov, Aleksandr; Scapin, Giovanna; Patel, Sangita B.; Roy, Ranabir Sinha; Wu, Joseph K.; Wyvratt, Matthew J.; Zhang, Bei B.; Zhu, Lan; Thornberry, Nancy A.; Weber, Ann E. [Journal of Medicinal Chemistry, 2005, vol. 48, # 1, p. 141 - 151]

16
[ 157911-56-3 ]
3-amino-1-(3-pentafluoroethyl-5,6-dihydro-8<i>H</i>-[1,2,4]triazolo[4,3-<i>a</i>]pyrazin-7-yl)-4-(2,4,5-trifluoro-phenyl)-butan-1-one; hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: n-BuLi / tetrahydrofuran / -78 °C 1.2: tetrahydrofuran / -78 °C 2.1: aq. HCl / acetonitrile / 72 h / 20 °C 2.2: 2.41 g / triethylamine / CH₂Cl₂ / 16 h / 20 °C 3.1: aq. LiOH / tetrahydrofuran / 20 °C 4.1: isobutyl chloroformate; triethylamine / diethyl ether / 0.25 h / -20 °C 4.2: 0.36 g / diethyl ether / 1 h 5.1: 401 mg / aq. silver benzoate / dioxane / 2 h / 20 °C / sonication 6.1: HOBT; EDC; DIPEA / dimethylformamide / 20 °C 7.1: HCl / methanol / 20 °C

Reference： [1]Kim, Dooseop; Wang, Liping; Beconi, Maria; Eiermann, George J.; Fisher, Michael H.; He, Huaibing; Hickey, Gerard J.; Kowalchick, Jennifer E.; Leiting, Barbara; Lyons, Kathryn; Marsilio, Frank; McCann, Margaret E.; Patel, Reshma A.; Petrov, Aleksandr; Scapin, Giovanna; Patel, Sangita B.; Roy, Ranabir Sinha; Wu, Joseph K.; Wyvratt, Matthew J.; Zhang, Bei B.; Zhu, Lan; Thornberry, Nancy A.; Weber, Ann E. [Journal of Medicinal Chemistry, 2005, vol. 48, # 1, p. 141 - 151]

17
[ 157911-56-3 ]
(L)-2-amino-3-(2,4,5-trifluorophenyl)propanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: Na; C₂H₅OH / 2 h / Heating 2: NaOH; HCl / methanol / 3 h / 40 °C 3: xylene / 2 h / 139 °C 4: NaOH; CH₃COONa; Aspergillus genus acylase / H₂O / 48 h / 38 °C

Reference： [1]Matsushima; Fujita; Okada; Shirasu; Nose; Shimohigashi [Bulletin of the Chemical Society of Japan, 2000, vol. 73, # 11, p. 2531 - 2538]

18
[ 157911-56-3 ]
(D)-2-amino-3-(2,4,5-trifluorophenyl)propanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: Na; C₂H₅OH / 2 h / Heating 2: NaOH; HCl / methanol / 3 h / 40 °C 3: xylene / 2 h / 139 °C 4: NaOH; CH₃COONa; Aspergillus genus acylase / H₂O / 48 h / 38 °C 5: HCl / dioxane / 5 h / Heating
	Multi-step reaction with 3 steps 1.1: sodium ethanolate / ethanol / 0.17 h / 20 °C 1.2: 6 h / Reflux 2.1: sodium hydroxide / methanol; water / 3 h / Reflux 2.2: Reflux 3.1: ammonium chloride; D-glucose; D-amino acid dehydrogenase from Corynebacterium glutamicum (variant Q₁₅₁L-D₁₅₅G-T₁₇₀I-R₁₉₆M-H₂₄₅N); glucose dehydrogenase from Bacillus megaterium; L-amino acid deaminase from Proteus mirabilis / aq. buffer / 12 h / 37 °C / Resolution of racemate; Enzymatic reaction

Reference： [1]Matsushima; Fujita; Okada; Shirasu; Nose; Shimohigashi [Bulletin of the Chemical Society of Japan, 2000, vol. 73, # 11, p. 2531 - 2538]
[2]Parmeggiani, Fabio; Rué Casamajo, Arnau; Colombo, Danilo; Ghezzi, Maria Chiara; Galman, James L.; Chica, Roberto A.; Brenna, Elisabetta; Turner, Nicholas J. [Green Chemistry, 2019, vol. 21, # 16, p. 4368 - 4379]

19
[ 157911-56-3 ]
[ 324028-04-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: Na; C₂H₅OH / 2 h / Heating 2: NaOH; HCl / methanol / 3 h / 40 °C 3: xylene / 2 h / 139 °C

Reference： [1]Matsushima; Fujita; Okada; Shirasu; Nose; Shimohigashi [Bulletin of the Chemical Society of Japan, 2000, vol. 73, # 11, p. 2531 - 2538]

20
[ 157911-56-3 ]
[ 324028-10-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: Na; C₂H₅OH / 2 h / Heating 2: NaOH; HCl / methanol / 3 h / 40 °C 3: xylene / 2 h / 139 °C 4: NaOH; CH₃COONa; Aspergillus genus acylase / H₂O / 48 h / 38 °C

Reference： [1]Matsushima; Fujita; Okada; Shirasu; Nose; Shimohigashi [Bulletin of the Chemical Society of Japan, 2000, vol. 73, # 11, p. 2531 - 2538]

21
[ 157911-56-3 ]
[ 324027-98-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: Na; C₂H₅OH / 2 h / Heating 2: NaOH; HCl / methanol / 3 h / 40 °C

Reference： [1]Matsushima; Fujita; Okada; Shirasu; Nose; Shimohigashi [Bulletin of the Chemical Society of Japan, 2000, vol. 73, # 11, p. 2531 - 2538]

22
[ 651047-29-9 ]
[ 157911-56-3 ]
[ 651047-30-2 ]

Yield	Reaction Conditions	Operation in experiment
96%	With potassium <i>tert</i>-butylate In tetrahydrofuran at 20℃; for 2h;	48.2 Step 2. 1- (2,4,5-trifluorobenzyl)-3-(4-tert-butoxycarbonyl-1-piperazinyl)-2(1H)-pyrazinone To a solution of 3-(4-tert-butoxycarbonyl-1-piperazinyl)-2(1H)-pyrazinone (obtained in Step 1 above ; 1.30 g, 4.66 mmol) in THF (20 mL) was added t-BuOK (0.53 g, 4.66 mmol) and the mixture was stirred at room temperature for 10 min. The resulting solution was added dropwise to a stirred solution of 2,4,5-trifluorobenzyl bromide (1.20 g, 5.33 mmol) in THF (20 ml) at room temperature. After 2 h, the reaction mixture was cooled to 0 C and partitioned between water (20 mL) and EtOAc (50 mL). The organic layer was washed with brine (10 mL) and dried over Na2SO4. Evaporation of the solvent gave 1. 82 g (96%) of the title compound as an oil which crystallized upon standing. The product can be recrystallized from tert-butyl methyl ether. HPLC purity: 94%.1NMR and MS analyses support the stated structure.

Reference： [1]Current Patent Assignee: SWEDISH ORPHAN BIOVITRUM AB - WO2004/9586, 2004, A1 Location in patent: Page 47; 48

23
[ 1072-83-9 ]
[ 157911-56-3 ]
4-[1-(2,4,5-trifluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		27 4-[1-(2,4,5-Trifluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid AI-3-25 EXAMPLE 27 4-[1-(2,4,5-Trifluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid AI-3-25 AI-3-25 was synthesised from 2-acetyl pyrrole and 2,4,5-trifluorobenzyl bromide in a manner similar to that described for AI-3-9 to afford the product as a brownish-yellow solid. melting point 154-156° C. (uncorrected). 1H NMR (400 MHz, DMSO) δ 7.6 (m, 1H), 7.48 (m, 2H), 6.86 (s, 1H), 6.78 (m, 1H), 6.36 (dd, J=2.5, 4.1 Hz, 1H), 5.66 (s, 2H).

Reference： [1]Current Patent Assignee: AMGEN INC - US6306891, 2001, B1

24
[ 913650-39-2 ]
[ 157911-56-3 ]
[ 913650-55-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate In acetone for 1 - 18h; Heating / reflux;	The ethyl 2-[(5-chloro-2-hydroxyphenyl)methyl]-1 ,3-thiazole-4-carboxylate was dissolved in acetone and potassium carbonate (2.5 to 5 equivalents) was added, followed by the appropriate benzyl bromide (1.1 to 2 equivalents). The reaction was stirred at reflux for between 1 and 18h. The mixture was filtered and the filtrate evaporated. The residue was purified by flash chromatography on silica

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2006/114274, 2006, A1 Location in patent: Page/Page column 47; 48

25
[ 121936-50-3 ]
trans-(4-Hydroxy-cyclohexyl)-(2,4,5-trifluoro-benzyl)-carbamic acid benzyl ester [ No CAS ]
[ 157911-56-3 ]

Yield	Reaction Conditions	Operation in experiment
		16.7 Example 16.7 Example 16.7 In analogy to examples 16.2 and 16.3, from trans-[4-(tert-Butyl-dimethyl-silanyloxy)-cyclohexyl]-carbamic acid benzyl ester and 2,4,5-trifluorobenzyl bromide, trans-(4-Hydroxy-cyclohexyl)-(2,4,5-trifluoro-benzyl)-carbamic acid benzyl ester was obtained as orange oil, MS: 394 (MH+).

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2002/45777, 2002, A1

26
[ 100-02-7 ]
[ 157911-56-3 ]
[ 630413-01-3 ]

Yield	Reaction Conditions	Operation in experiment
92%		27.a a a 1,2,4-Trifluoro-5-(4-nitro-phenoxymethyl)-benzene Prepared in analogy to example 8 from 4-nitrophenol and 2,4,5-trifluoro-benzylbromide. Colorless solid. Yield=92%. MS: m/e=283.0 (M+).

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2003/232883, 2003, A1

27
[ 952423-58-4 ]
[ 157911-56-3 ]
[ 952423-59-5 ]
[ 952506-22-8 ]

Yield	Reaction Conditions	Operation in experiment
65%	Stage #1: 2,4,5-trifluorobenzyl bromide With iodine; magnesium In cyclopentyl methyl ether; toluene at 20 - 28℃; Inert atmosphere; Stage #2: C₂₀H₂₈N₂O₃S In dichloromethane; cyclopropyl methyl ether; toluene at -55 - 20℃; diastereoselective reaction;

Reference： [1]Location in patent: experimental part Fei, Zhongbo; Wu, Quanbing; Zhang, Fei; Cao, Yudong; Liu, Chuanqin; Shieh, Wen-Chung; Xue, Song; McKenna, Joe; Prasad, Kapa; Prashad, Mahavir; Baeschlin, Daniel; Namoto, Kenji [Journal of Organic Chemistry, 2008, vol. 73, # 22, p. 9016 - 9021]

28
[ 7439-95-4 ]
[ 157911-56-3 ]
2,4,5-trifluorobenzylmagnesium bromide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In diethyl ether for 0.333333h; Heating / reflux;	1.2 A solution of 2044 µL (15.44 mmol) 1-bromomethyl-2,4,5-trifluoro-benzene in 2 mL diethyl ether is slowly added into a suspension of 375 mg (15.44 mmol) magnesium turnings in 2 mL diethyl ether. After the reaction is initiated, the reaction mixture is maintained at reflux during the addition of the benzylbromide. After 20 min the mixture is directly added to a solution of 1220 mg (3.86 mmol) 4-[(E)-2-methyl-propane-2-sulfinylimino]-methyl}-piperidine-1-carboxylic acid tert-butylester in 60 mL DCM at -78°C. The mixture is stirred at -78°C for 2 h and then allowed to reach ambient temperature. Stirring is continued overnight. When complete, the reaction mixture is quenched by addition of water and extracted with diethyl ether. The combined organic layers are dried over sodium sulfate and the solvent is removed under reduced pressure. The residue is purified by flash chromatography (hexane/ethyl acetate) to yield the desired S/R diastereomer. LC/MS (I) (5-95%, 5 min): rt 4.60, m/z 407 [M-56+H]+, 363 [M-Boc+H]+. 1H-NMR (400 MHz, DMSO-d6) δ = 1.08 (s, 9H), 1.12-1.26 (m, 2H), 1.37 (s, 9H), 1.42-1.71 (m, 3H), 2.60-2.64 (m, 2H), 2.79-2.88 (m, 2H), 3.25 (m, 1 H), 3.93 (m, 2H), 4,91 (d, J = 6.6 Hz, 1H), 7.41-7.54 (m, 2H).

Reference： [1]Current Patent Assignee: SWEDISH ORPHAN BIOVITRUM AB; SANTHERA PHARMACEUTICALS HOLDING AG - EP2019099, 2009, A1 Location in patent: Page/Page column 12-13

29
[ 1133810-75-9 ]
[ 157911-56-3 ]
methyl-(2S)-2-(tert-butoxycarbonyl)-amino-2-[8-(2,4,5-trifluorobenzyl)-8-aza-bicyclo[3.2.1]-oct-3-yl]-exo-acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With triethylamine In dichloromethane at 0 - 20℃; for 3h;	Methyl-(2S)-2-(tert-butoxycarbonyl)-amino-2- [8-aza-bicyclo [3.2.1]-oct-3-yl]-exo- acetate (step-5 of intermediate 2, 2.1g, 7.04 mmol) was dissolved in dichloromethane (70 ml). The reaction mixture was cooled to 0°C and added triethylamine (1.06g, 1.4ml, 10.6 mmol) followed by the addition of a solution of 2,4,5- trifluorobenzyl bromide (1.58g, 7.04 mmol) in dichloromethane (14 ml). The reaction mixture was then stirred at room temperature for 3 hours. The solvent was removed under reduced pressure to yield the crude product, which was purified by column chromatography over silica gel (100-200 mesh) using 1% methanol as an eluent to yield the title compound (2.2g, 71 %). MS: m/z 443(M+1)1HNMR (CDCI3+D2O, 400 MHz):δ 1.42-1.47 (m, 9H), 1.5-1.66 (m, 6H), 1.9-2.05 (m, 3H), 3.16 (s, 2H), 3.73 (s, 3H), 4.1-4.3 (m, 2H), 5.0-5.1 (m, 1H), 6.8-6.9 (m, 1H), 7.4-7.46 (m, 1 H).

Reference： [1]Current Patent Assignee: LUPIN LIMITED - WO2009/37719, 2009, A1 Location in patent: Page/Page column 64; 65

30
[ 1256768-32-7 ]
[ 157911-56-3 ]
[ 1256768-41-8 ]

Yield	Reaction Conditions	Operation in experiment
73%	With potassium carbonate In acetonitrle at 70℃; for 2h;

Reference： [1]Location in patent: experimental part Chen, Xin; Zhu, Changjin; Guo, Fan; Qiu, Xiaowei; Yang, Yanchun; Zhang, Shuzhen; He, Minlan; Parveen, Shagufta; Jing, Chaojun; Li, Yan; Ma, Bing [Journal of Medicinal Chemistry, 2010, vol. 53, # 23, p. 8330 - 8344]

31
[ 1256768-33-8 ]
[ 157911-56-3 ]
[ 1256768-46-3 ]

Yield	Reaction Conditions	Operation in experiment
84%	With potassium carbonate In acetonitrle at 70℃; for 2h;

Reference： [1]Location in patent: experimental part Chen, Xin; Zhu, Changjin; Guo, Fan; Qiu, Xiaowei; Yang, Yanchun; Zhang, Shuzhen; He, Minlan; Parveen, Shagufta; Jing, Chaojun; Li, Yan; Ma, Bing [Journal of Medicinal Chemistry, 2010, vol. 53, # 23, p. 8330 - 8344]

32
[ 1256768-34-9 ]
[ 157911-56-3 ]
[ 1256768-49-6 ]

Yield	Reaction Conditions	Operation in experiment
80%	With potassium carbonate In acetonitrle at 70℃; for 2h;

Reference： [1]Location in patent: experimental part Chen, Xin; Zhu, Changjin; Guo, Fan; Qiu, Xiaowei; Yang, Yanchun; Zhang, Shuzhen; He, Minlan; Parveen, Shagufta; Jing, Chaojun; Li, Yan; Ma, Bing [Journal of Medicinal Chemistry, 2010, vol. 53, # 23, p. 8330 - 8344]

33
[ 1256768-35-0 ]
[ 157911-56-3 ]
[ 1256768-53-2 ]

Yield	Reaction Conditions	Operation in experiment
79%	With potassium carbonate In acetonitrle at 70℃; for 2h;

Reference： [1]Location in patent: experimental part Chen, Xin; Zhu, Changjin; Guo, Fan; Qiu, Xiaowei; Yang, Yanchun; Zhang, Shuzhen; He, Minlan; Parveen, Shagufta; Jing, Chaojun; Li, Yan; Ma, Bing [Journal of Medicinal Chemistry, 2010, vol. 53, # 23, p. 8330 - 8344]

34
[ 359-85-3 ]
[ 157911-56-3 ]
[ 1256768-91-8 ]

Yield	Reaction Conditions	Operation in experiment
76%	With potassium carbonate In acetonitrile at 70℃; for 2h;

Reference： [1]Location in patent: experimental part Chen, Xin; Zhu, Changjin; Guo, Fan; Qiu, Xiaowei; Yang, Yanchun; Zhang, Shuzhen; He, Minlan; Parveen, Shagufta; Jing, Chaojun; Li, Yan; Ma, Bing [Journal of Medicinal Chemistry, 2010, vol. 53, # 23, p. 8330 - 8344]

35
[ 1298029-74-9 ]
[ 157911-56-3 ]
[ 1298029-80-7 ]

Yield	Reaction Conditions	Operation in experiment
71%	With potassium carbonate In acetonitrile at 70℃; for 2h;	7.6. General procedure for the synthesis of [2-benzyl-3,4-dihydro-2H-pyrido[2,3-e]-[1,2,4]-thiadiazine 1,1-dioxide-4-yl] acetic acid methyl esters (6a-6o) General procedure: A mixture of the appropriate (3,4-dihydro-2H-pyrido[2,3-e]-[1,2,4]-thiadiazine 1,1-dioxide-4-yl) acetic acid methyl ester (5a-5c, 2 mmol), potassium carbonate (1 g), and the appropriate benzyl bromide (2.1 mmol) in acetonitrile (30 mL) was heated at 70 °C for 2 h. After evaporation of the solvent under reduced pressure, the crude solid was washed with water, dried, and then recrystallized in ethyl acetate to give pure product.

Reference： [1]Location in patent: experimental part Chen, Xin; Yang, Yanchun; Ma, Bing; Zhang, Shuzhen; He, Minlan; Gui, Dequan; Hussain, Saghir; Jing, Chaojun; Zhu, Changjin; Yu, Qun; Liu, Yan [European Journal of Medicinal Chemistry, 2011, vol. 46, # 5, p. 1536 - 1544]

36
[ 1298029-75-0 ]
[ 157911-56-3 ]
[ 1298029-85-2 ]

Yield	Reaction Conditions	Operation in experiment
66%	With potassium carbonate In acetonitrile at 70℃; for 2h;	7.6. General procedure for the synthesis of [2-benzyl-3,4-dihydro-2H-pyrido[2,3-e]-[1,2,4]-thiadiazine 1,1-dioxide-4-yl] acetic acid methyl esters (6a-6o) General procedure: A mixture of the appropriate (3,4-dihydro-2H-pyrido[2,3-e]-[1,2,4]-thiadiazine 1,1-dioxide-4-yl) acetic acid methyl ester (5a-5c, 2 mmol), potassium carbonate (1 g), and the appropriate benzyl bromide (2.1 mmol) in acetonitrile (30 mL) was heated at 70 °C for 2 h. After evaporation of the solvent under reduced pressure, the crude solid was washed with water, dried, and then recrystallized in ethyl acetate to give pure product.

Reference： [1]Location in patent: experimental part Chen, Xin; Yang, Yanchun; Ma, Bing; Zhang, Shuzhen; He, Minlan; Gui, Dequan; Hussain, Saghir; Jing, Chaojun; Zhu, Changjin; Yu, Qun; Liu, Yan [European Journal of Medicinal Chemistry, 2011, vol. 46, # 5, p. 1536 - 1544]

37
[ 1298029-76-1 ]
[ 157911-56-3 ]
[ 1298029-90-9 ]

Yield	Reaction Conditions	Operation in experiment
74%	With potassium carbonate In acetonitrile at 70℃; for 2h;	7.6. General procedure for the synthesis of [2-benzyl-3,4-dihydro-2H-pyrido[2,3-e]-[1,2,4]-thiadiazine 1,1-dioxide-4-yl] acetic acid methyl esters (6a-6o) General procedure: A mixture of the appropriate (3,4-dihydro-2H-pyrido[2,3-e]-[1,2,4]-thiadiazine 1,1-dioxide-4-yl) acetic acid methyl ester (5a-5c, 2 mmol), potassium carbonate (1 g), and the appropriate benzyl bromide (2.1 mmol) in acetonitrile (30 mL) was heated at 70 °C for 2 h. After evaporation of the solvent under reduced pressure, the crude solid was washed with water, dried, and then recrystallized in ethyl acetate to give pure product.

Reference： [1]Location in patent: experimental part Chen, Xin; Yang, Yanchun; Ma, Bing; Zhang, Shuzhen; He, Minlan; Gui, Dequan; Hussain, Saghir; Jing, Chaojun; Zhu, Changjin; Yu, Qun; Liu, Yan [European Journal of Medicinal Chemistry, 2011, vol. 46, # 5, p. 1536 - 1544]

38
N₁-Boc-benzimidazol-5-amine [ No CAS ]
[ 157911-56-3 ]
[ 1342887-20-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate	18 N,N-Bis(2,4,5-trifluorobenzyl)-1H-benzo[d]imidazol-5-amine Example 18 N,N-Bis(2,4,5-trifluorobenzyl)-1H-benzo[d]imidazol-5-amine The compound was synthesized starting from N1-Boc-benzimidazol-5-amine (233 mg; 1 mmol; 1 eq.), 2,4,5-trifluorbenzylbromide (563 mg; 2.5 mmol; 2.5 eq.) and K2CO3 (345 mg; 2.5 mmol; 2.5 eq.) according to method 4; Yield: 0.172 (40.9%); MS m/z: 422.2 [M+H]+; 1H-NMR (500 MHz, DMSO d6): δ 4.68 (s, 4H); 6.74 (dd, 1H, 4J=2.1 Hz, 3J=8.9 Hz); 6.78 (br s, 1H); 7.23-7.29 (m, 2H); 7.39 (d, 1H, 3J=8.9 Hz); 7.51-7.56 (m, 2H); 7.97 (s, 1H); 12.03 (br s, 1H); HPLC (METHOD [A]): rt 16.46 min (100%)

Reference： [1]Current Patent Assignee: VIVORYON THERAPEUTICS AG - US2011/262388, 2011, A1

39
[ 1342887-13-1 ]
[ 157911-56-3 ]
[ 1342888-10-1 ]

Yield	Reaction Conditions	Operation in experiment
0.134 g (31.3%)	With potassium carbonate	61 N-(2,4,5-Trifluorobenzyl)-N-(4-(methylthio)benzyl)-1H-benzo[d]imidazol-5-amine Example 61 N-(2,4,5-Trifluorobenzyl)-N-(4-(methylthio)benzyl)-1H-benzo[d]imidazol-5-amine The compound was synthesized starting from N-(4-methylthio)benzyl-benzimidazol-5-amine (270 mg; 1 mmol; 1 eq.), 2,4,5-trifluorobenzylbromide (248 mg; 1.1 mmol; 1.1 eq.) and K2CO3 (152 mg; 1.1 mmol; 1.1 eq.) according to method 6; Yield: 0.134 g (31.3%); MS m/z: 414.2 [M+H]+; 1H-NMR (400 MHz, DMSO d6): δ 2.41 (s, 3H); 4.62 (s, 2H); 4.63 (s, 2H); 6.72-6.74 (m, 2H); 7.17-7.21 (m, 5H); 7.34-7.35 (m, 1H); 7.50-7.56 (m, 1H); 7.92 (s, 1H); 11.94 (br s, 1H); HPLC (METHOD [A]): rt 17.22 min (100%)

Reference： [1]Current Patent Assignee: VIVORYON THERAPEUTICS AG - US2011/262388, 2011, A1

40
[ 5510-31-6 ]
[ 157911-56-3 ]
C₁₇H₁₄F₃NO₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate In acetonitrile at 70℃; for 2h;	5.5. General synthetic procedure for 5a-e General procedure: To a solution of 4 (43.1 g, 220 mmol), in benzene (300 mL) were added p-toluenesulfonic acid (PTSA) (2.6 g, 14.0 mmol) and ethylene glycol (31 mL, 550 mmol). The reaction mixture was refluxed in a Dean and Stark apparatus for 3 h. The crude material was then poured into ice-water mixture and the precipitate was collected by suction filtration, washed with cold water and dried in vacuo to leave the product, which was used without further purification. A mixture of the dioxolane (4.9 g, 20 mmol), potassium carbonate (3 g), and appropriate benzyl bromide (20 mmol) in acetonitrile (50 mL) was heated at 70 °C for 2 h. After evaporation of the solvent under reduced pressure, the resulting dioxolane was added to 40 mL tetrahydrofuran and 30 mL 10% hydrochloric acid and stirred at 80 °C for 6 h. The reaction mixture was poured into water with vigorous stirring. After 30 min, filtration afforded the desired product, which was used without further purification.

Reference： [1]Location in patent: experimental part Chen, Xin; Zhang, Shuzhen; Yang, Yanchun; Hussain, Saghir; He, Minlan; Gui, Dequan; Ma, Bing; Jing, Chaojun; Qiao, Zhixin; Zhu, Changjin; Yu, Qun [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 23, p. 7262 - 7269]

41
[ 89532-94-5 ]
[ 157911-56-3 ]
[ 1297284-82-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate In N,N-dimethyl-formamide at 90℃; Inert atmosphere;

Reference： [1]Location in patent: experimental part Kaila, Neelu; Huang, Adrian; Moretto, Alessandro; Follows, Bruce; Janz, Kristin; Lowe, Michael; Thomason, Jennifer; Mansour, Tarek S.; Hubeau, Cedric; Page, Karen; Morgan, Paul; Fish, Susan; Xu, Xin; Williams, Cara; Saiah, Eddine [Journal of Medicinal Chemistry, 2012, vol. 55, # 11, p. 5088 - 5109]

42
quinindine [ No CAS ]
[ 157911-56-3 ]
N-(2,4,5-trifluorobenzyl)quinidinium bromide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	In toluene at 80℃; for 12h; Inert atmosphere;

Reference： [1]Wu, Shaoxiang; Zeng, Wei; Wang, Qi; Chen, Fu-Xue [Organic and Biomolecular Chemistry, 2012, vol. 10, # 47, p. 9334 - 9337]

43
[ 157911-56-3 ]
[ 56-54-2 ]
[ 1415666-61-3 ]

Yield	Reaction Conditions	Operation in experiment
69%	In toluene at 80℃; Inert atmosphere;	5 Ammonium bromides of cinchona alkaloids; general procedure General procedure: To a flame-dried flask equipped with a magnetic stirring bar and a condenser was added with cinchona alkaloids (1 mmol), toluene (5 mL), and benzyl bromide derivatives (1.2 mmol, 1.2 equiv.). The mixture was heated at 80 8C until a TLC analysis showing that the starting material was completely consumed. Cooled to room temperature and poured onto Et2O (30 mL) with stirring, the resulting suspension was stirred for another 1 h. Then the precipitate was purified by flash chromatography (MeOH/EtOAc = 1/10, V/V). 4.24.5 N-(2,4,5-Trifluorobenzyl)quinidinium bromide (1e) Yield: 69%; white solid; m.p. 182-185 °C (decomp.); [α]D28 +194.8 (c 0.19, CH3OH); IR (KBr): 3394, 3198, 3006, 1621, 1520, 1473, 1469, 1431, 1338, 1259, 1241, 1226, 1205, 1158, 1113, 1026, 851, 828, 719 cm-1; 1H NMR (400 MHz, DMSO-d6): δ = 8.82 (d, J = 4.4 Hz, 1H), 8.16-8.10 (m, 1H), 8.02 (d, J = 9.2 Hz, 1H), 7.91-7.85 (m, 1H), 7.76 (d, J = 4.4 Hz, 1H), 7.50 (dd, J = 9.6, 2.8 Hz, 1H), 7.40 (d, J = 2.4 Hz, 1H), 6.84 (d, J = 2.8 Hz, 1H), 6.50 (s, 1H), 6.03 (ddd, J = 17.2, 10.4, 6.8 Hz, 1H), 5.26-5.21 (m, 2H), 5.01 (d, J = 12.8 Hz, 1H), 4.77 (d, J = 13.6 Hz, 1H), 4.23-4.18 (m, 1H), 4.06 (s, 3H), 3.94-3.82 (m, 2H), 3.49 (t, J = 11.4 Hz, 1H), 3.22-3.15 (m, 1H), 2.67-2.60 (m, 1H), 2.36 (t, J = 11.8 Hz, 1H), 1.90 (s, 1H), 1.84-1.75 (m, 2H), 1.10-1.05 (m, 1H); 13C NMR (100 MHz, DMSO-d6): δ = 158.0 (ddd, J = 244.1, 9.9, 2.3 Hz), 157.9, 151.5 (dt, J = 251.2, 13.6 Hz), 147.9, 146.7 (ddd, J = 241.8, 12.6, 2.4 Hz), 144.2, 143.7, 137.7, 131.9, 125.9, 123.8 (dd, J = 19.1, 2.7 Hz), 122.0, 120.7, 117.6, 112.8 (dt, J = 17.0, 5.6 Hz), 107.5 (dd, J = 29.5, 21.4 Hz), 102.7, 68.0, 65.3, 56.4, 56.1, 56.0, 54.7, 37.5, 26.6, 23.7, 21.0; HRMS calcd for [C27H28F3N2O2]+: 469.2097, found 469.2098.
69%	In toluene at 80℃; for 12h;

Reference： [1]Wu, Shaoxiang; Guo, Jiyi; Sohail, Muhammad; Cao, Chengyao; Chen, Fu-Xue [Journal of Fluorine Chemistry, 2013, vol. 148, p. 19 - 29]
[2]Wu, Shaoxiang; Pan, Dong; Cao, Chengyao; Wang, Qi; Chen, Fu-Xue [Advanced Synthesis and Catalysis, 2013, vol. 355, # 10, p. 1917 - 1923]

44
[ 1432503-56-4 ]
[ 157911-56-3 ]
[ 1432503-60-0 ]

Yield	Reaction Conditions	Operation in experiment
83%	With potassium carbonate In acetonitrile at 70℃; for 2h;