113211-94-2

Basic information

• Product Name: 2,3-Difluorobenzyl bromide
• Synonyms: TIMTEC-BB SBB006681;1-(BROMOMETHYL)-2,3-DIFLUORO-BENZENE;2,3-DIFLUOROBENZYL BROMIDE;ALPHA-BROMO-2,3-DIFLUOROTOLUENE;Benzene, 1-(bromomethyl)-2,3-difluoro-;à-bromo-2,3-difluorotoluene;α-bromo-2,3-difluorotoluene;2,3-Difluorobenzyl bromide 98%
• CAS NO: 113211-94-2
• Molecular Formula: C₇H₅BrF₂
• Molecular Weight: 207.02
• Product Categories: Fluoro-contained benzyl bromide series;Aromatic compound;Miscellaneous;Benzenes
• Mol File: 113211-94-2.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 190.5 °C at 760 mmHg
• Flash Point: 194 °F
• Appearance: clear colorless to light yellow liquid
• Density: 1.628 g/mL at 25 °C(lit.)
• Vapor Pressure: 98.1mmHg at 25°C
• Refractive Index: n20/D 1.528(lit.)
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Sensitive: Lachrymatory
• BRN: 7089244
• CAS DataBase Reference: 2,3-Difluorobenzyl bromide(CAS DataBase Reference)
• NIST Chemistry Reference: 2,3-Difluorobenzyl bromide(113211-94-2)
• EPA Substance Registry System: 2,3-Difluorobenzyl bromide(113211-94-2)

Safety Data

• Hazard Codes: C,Xi
• Statements: 34-36/37/38
• Safety Statements: 26-36/37/39-45-25-36/37
• RIDADR: UN 3265 8/PG 2
• WGK Germany: 3
• F: 10-19-21
• HazardClass: 8
• PackingGroup: III
• Hazardous Substances Data: 113211-94-2(Hazardous Substances Data)

Usage

Chemical Properties

clear colorless to light yellow liquid

Uses

2,3-Difluorobenzyl bromide was used in the synthesis of chemokine antagonists.

InChI:InChI=1/C4F7I/c5-1(2(6)12)3(7,8)4(9,10)11/b2-1-

Synthetic route

(2,3-difluoro-phenyl)-methanol (75853-18-8) → 2,3-difluorobenzyl bromide (113211-94-2)

Conditions	Yield
With phosphorus tribromide In toluene at 100℃; for 1h;	61%
With phosphorus tribromide In diethyl ether at -10℃; for 1.25h;	20 g

2,3-difluorobenzoic acid (4519-39-5) → 2,3-difluorobenzyl bromide (113211-94-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 40 percent / B2H6 / tetrahydrofuran / 1.5 h 2: 61 percent / PBr3 / toluene / 1 h / 100 °C View Scheme

2,3-difluorobenzaldehyde (2646-91-5) → 2,3-difluorobenzyl bromide (113211-94-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol; sodium tetrahydroborate / 1 h / 0 - 50 °C 2: phosphorus tribromide / diethyl ether / 1.25 h / -10 °C View Scheme

C23H30BrNO5S + 2,3-difluorobenzyl bromide (113211-94-2) → C30H34BrF2NO5S

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 18h;	96%

potassium phtalimide (1074-82-4) + 2,3-difluorobenzyl bromide (113211-94-2) → 2-(3-chloro-2-fluorobenzyl)-4,5-dihydroxyisoindoline-1,3-dione (923845-93-6)

Conditions	Yield
In N,N-dimethyl-formamide at 120℃; for 2.5h;	92%

2,3-difluorobenzyl bromide (113211-94-2) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → 2-acetylamino-2-(2,3-difluoro-benzyl)-malonic acid diethyl ester (266360-43-4)

Conditions	Yield
With sodium ethanolate In ethanol for 2h; Alkylation; Heating;	90%

2,3-difluorobenzyl bromide (113211-94-2) → 1-(2,3-difluorobenzyl)-3-(4-methoxy-3-(3R)-tetrahydrofuranyloxyphenyl)-1H-pyrazole + 1-(2,3-difluorobenzyl)-5-[4-methoxy-3-(3R)-tetrahydrofuranyloxy-phenyl]-1H-pyrazole

Conditions	Yield
Stage #1: 3-[4-methoxy-3-(3R)-tetrahydrofuranyloxyphenyl]-1H-pyrazole With sodium hydride In DMF (N,N-dimethyl-formamide) at 20℃; for 3h; Stage #2: 2,3-difluorobenzyl bromide In DMF (N,N-dimethyl-formamide) at 20℃; for 16h;	A 90% B n/a

3-(4-methoxy-3-(3R)-tetrahydrofuranyloxyphenyl)-1H-pyrazole + 2,3-difluorobenzyl bromide (113211-94-2) → 1-(2,3-difluorobenzyl)-3-(4-methoxy-3-(3R)-tetrahydrofuranyloxyphenyl)-1H-pyrazole + 1-(2,3-difluorobenzyl)-5-[4-methoxy-3-(3R)-tetrahydrofuranyloxy-phenyl]-1H-pyrazole

Conditions	Yield
Stage #1: 3-(4-methoxy-3-(3R)-tetrahydrofuranyloxyphenyl)-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide at 20℃; for 3h; Stage #2: 2,3-difluorobenzyl bromide In N,N-dimethyl-formamide at 20℃; for 16h;	A 90% B n/a

3-[4-methoxy-3-(3R)-tetrahydrofuranyloxyphenyl]-1H-pyrazole (784189-75-9) + 2,3-difluorobenzyl bromide (113211-94-2) → 1-(2,3-difluorobenzyl)-3-(4-methoxy-3-(3R)-tetrahydrofuranyloxyphenyl)-1H-pyrazole + 1-(2,3-difluorobenzyl)-5-[4-methoxy-3-(3R)-tetrahydrofuranyloxy-phenyl]-1H-pyrazole

Conditions	Yield
Stage #1: 3-[4-methoxy-3-(3R)-tetrahydrofuranyloxyphenyl]-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide at 20℃; for 3h; Stage #2: 2,3-difluorobenzyl bromide In N,N-dimethyl-formamide at 20℃; for 16h;	A 90% B n/a

2-nitropropane (79-46-9) + 2,3-difluorobenzyl bromide (113211-94-2) → 1-(2,3-difluoro-phenyl)-2-methyl-2-nitro-propan-1-ol + 2,3-difluorobenzaldehyde (2646-91-5)

Conditions	Yield
With tetrabutyl ammonium fluoride In tetrahydrofuran Hass-Bender/Henry reaction;	A 89% B n/a

4-aminothiouracil (1004-40-6) + 2,3-difluorobenzyl bromide (113211-94-2) → 6-amino-2-[[(2,3-difluorophenyl)methyl]thio]-4-pyrimidinol (503271-69-0)

Conditions	Yield
With potassium hydroxide In N,N-dimethyl-formamide	89%
With sodium hydroxide In tetrahydrofuran; water at 20℃; for 3.91667h;

2-(2-methyl-3-((6-oxo-1,6-dihydropyridazin-3-yl)methyl)-1H-indol-1-yl)-acetic acid (1297284-31-1) + 2,3-difluorobenzyl bromide (113211-94-2) → 2,3-difluorobenzyl 2-(3-((1-(2,3-difluorobenzyl)-6-oxo-1,6-dihydro-pyridazin-3-yl)methyl)-2-methyl-1H-indol-1-yl)acetate (1297284-38-8)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 85℃; for 16h; Inert atmosphere;	89%

cis 1-(1,3-benzodioxol-5-yl)-4-(1-piperazinyl)cyclohexanol + 2,3-difluorobenzyl bromide (113211-94-2) → Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2,3-difluorophenyl)methyl]-1-piperazinyl]cyclohexanol

Conditions	Yield
	88.5%

6-ethyl-3-mercapto-1,2,4-triazin-5(2H)-one (452-12-0) + 2,3-difluorobenzyl bromide (113211-94-2) → 3-[(2,3-difluorobenzyl)thio]-6-ethyl-1,2,4-triazin-5(2H)-one (892592-68-6)

Conditions	Yield
With potassium carbonate In water	88%

3-iodine-6-methyl-1H-pyrazolo[3,4-b]pyridine + 2,3-difluorobenzyl bromide (113211-94-2) → 1-(2,3-difluorobenzyl)-3-iodo-6-methyl-1H-pyrazolo[3,4-b]pyridine

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 0℃; for 7h;	87%
With caesium carbonate In N,N-dimethyl-formamide at 0 - 20℃;

Methyl 5,6,7,8-tetrahydrocarbazole-1-carboxylate (59003-26-8) + 2,3-difluorobenzyl bromide (113211-94-2) → methyl 9-(2,3-difluorobenzyl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxylate

Conditions	Yield
Stage #1: Methyl 5,6,7,8-tetrahydrocarbazole-1-carboxylate With potassium hydroxide In dimethyl sulfoxide at 20℃; for 0.0833333h; Stage #2: 2,3-difluorobenzyl bromide In dimethyl sulfoxide for 0.333333h;	82%

4-aminothiouracil (1004-40-6) + 2,3-difluorobenzyl bromide (113211-94-2) → 6-amino-2-[[(2,3-difluorophenyl)methyl]thio]-4(3H)-pyrimidinone (503271-69-0)

Conditions	Yield
Stage #1: 4-aminothiouracil With sodium hydride In DMF (N,N-dimethyl-formamide) for 1h; Stage #2: 2,3-difluorobenzyl bromide In DMF (N,N-dimethyl-formamide) at 20℃;	81%
Stage #1: 4-aminothiouracil With potassium hydroxide In DMF (N,N-dimethyl-formamide); water for 0.5h; Stage #2: 2,3-difluorobenzyl bromide In tetrahydrofuran; DMF (N,N-dimethyl-formamide); water for 20h;
Stage #1: 4-aminothiouracil With sodium hydride In DMF (N,N-dimethyl-formamide) for 1h; Stage #2: 2,3-difluorobenzyl bromide In DMF (N,N-dimethyl-formamide) at 20℃;

ethyl 9H-pyrido[3,4-b]indole-3-carboxylate (74214-62-3) + 2,3-difluorobenzyl bromide (113211-94-2) → 2,9-bis(2,3-difluorobenzyl)-β-carbolineum bromide

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; mineral oil for 3h; Reflux;	81%

1H-pyrazolo[3,4-b]pyridine-3-carbonitrile (956010-88-1) + 2,3-difluorobenzyl bromide (113211-94-2) → 1-(2,3-difluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile (627076-46-4)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 16h; Inert atmosphere;	75%

5-chlorosalicyclaldehyde (635-93-8) + 2,3-difluorobenzyl bromide (113211-94-2) → 5-chloro-2-(2,3-difluorobenzyloxy)-benzaldehyde (632627-61-3)

Conditions	Yield
With potassium carbonate In DMF (N,N-dimethyl-formamide) at 60℃; for 3h;	74.3%

ethyl 6-mercaptocyclohex-1-ene-1-carboxylate (1028450-05-6) + 2,3-difluorobenzyl bromide (113211-94-2) → ethyl 6-[(2,3-difluorobenzyl)sulfanyl]cyclohex-1-ene-1-carboxylate (1028450-19-2)

Conditions	Yield
In N,N-dimethyl-formamide	74%

2,3-difluorobenzyl bromide (113211-94-2) + trans-4-(trans-4'-propyl cyclohexyl)-cyclohexane carboxylic acid chloride (83860-52-0) → C23H32F2O

Conditions	Yield
With zinc; palladium diacetate; triphenylphosphine In diethylene glycol dimethyl ether at 0℃; for 5h;	73%

2-pyrrolidinon (616-45-5) + 2,3-difluorobenzyl bromide (113211-94-2) → 1-(2,3-difluorobenzyl)pyrrolidin-2-one (1418719-35-3)

Conditions	Yield
Stage #1: 2-pyrrolidinon With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; under 760.051 Torr; for 2.16667h; Inert atmosphere; Stage #2: 2,3-difluorobenzyl bromide In N,N-dimethyl-formamide; mineral oil at 20℃; under 760.051 Torr; for 2.75h;	71.2%

tert-butyl acetoacetate (1694-31-1) + 2,3-difluorobenzyl bromide (113211-94-2) → 5-(2,3-difluorophenyl)-3-oxopentanoic acid tert-butyl ester (412950-60-8)

Conditions	Yield
Stage #1: tert-butyl acetoacetate With sodium hydride In tetrahydrofuran at 0℃; for 0.25h; Stage #2: With n-butyllithium In tetrahydrofuran; hexanes at 10℃; for 0.333333h; Stage #3: 2,3-difluorobenzyl bromide In tetrahydrofuran; hexanes at 20℃; for 0.25h;	71%

2-pyrrole aldehyde (1003-29-8) + 2,3-difluorobenzyl bromide (113211-94-2) → 1-[(2,3-difluorophenyl)methyl]pyrrole-2-carboxaldehyde (1482542-00-6)

Conditions	Yield
With sodium hydroxide In N,N-dimethyl-formamide at 20℃;	71%

5-fluoro-3-iodo-6-methyl-1H-pyrazolo[3,4-b]pyridine (1426309-26-3) + 2,3-difluorobenzyl bromide (113211-94-2) → 1-(2,3-difluorobenzyl)-5-fluoro-3-iodo-6-methyl-1H-pyrazolo[3,4-b]pyridine

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 20℃;	71%
With caesium carbonate In N,N-dimethyl-formamide at 20℃;	71%
With caesium carbonate In N,N-dimethyl-formamide at 20℃;	71%
With caesium carbonate In N,N-dimethyl-formamide at 20℃;	71%

2,3-difluorobenzyl bromide (113211-94-2) → (4S)-4-(3-cyclopentyloxy-4-methoxyphenyl)-1-(2,3-difluorobenzyl)-2-pyrrolidone (514215-43-1)

Conditions	Yield
Stage #1: Rolipram With 15-crown-5; sodium hydride In N,N-dimethyl-formamide at 20℃; for 3h; Stage #2: 2,3-difluorobenzyl bromide In tetrahydrofuran; N,N-dimethyl-formamide at 0 - 20℃; for 6h;	70%

(S)-rolipram (85416-73-5) + 2,3-difluorobenzyl bromide (113211-94-2) → (4S)-4-(3-cyclopentyloxy-4-methoxyphenyl)-1-(2,3-difluorobenzyl)-2-pyrrolidone (514215-43-1)

Conditions	Yield
Stage #1: (S)-rolipram With sodium hydride; 15-crown-5 In DMF (N,N-dimethyl-formamide) at 20℃; for 3h; Stage #2: 2,3-difluorobenzyl bromide In tetrahydrofuran; DMF (N,N-dimethyl-formamide) at 0 - 20℃; for 6h;	70%

1-tert-butoxycarbonyl-4-cyanopiperidine (91419-52-2) + 2,3-difluorobenzyl bromide (113211-94-2) → tert-butyl 4-cyano-4-(2,3-difluorobenzyl)piperidine-1-carboxylate

Conditions	Yield
Stage #1: 1-tert-butoxycarbonyl-4-cyanopiperidine With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1h; Stage #2: 2,3-difluorobenzyl bromide In tetrahydrofuran at 20℃; for 16h;	69.1%

trans-4-n-propylcyclohexylcarbonyl chloride (67679-83-8) + 2,3-difluorobenzyl bromide (113211-94-2) → C17H22F2O

Conditions	Yield
With zinc; palladium diacetate; triphenylphosphine In diethylene glycol dimethyl ether at 0 - 20℃; for 1h; Product distribution / selectivity;	67%

Upstream product

• 2646-91-5 2,3-difluorobenzaldehyde 
• 4519-39-5 2,3-difluorobenzoic acid 
• 75853-18-8 (2,3-difluoro-phenyl)-methanol 

Downstream Products

• 266360-43-4 2-acetylamino-2-(2,3-difluoro-benzyl)-malonic acid diethyl ester 
• 354582-93-7 2,6-bis[[(2,3-difluorophenyl)methyl]thio]-4,5-pyrimidinediamine 
• 514215-43-1 (4S)-4-(3-cyclopentyloxy-4-methoxyphenyl)-1-(2,3-difluorobenzyl)-2-pyrrolidone 
• 412950-51-7 (2,3-difluorophenyl)methanethiol 
• 354582-51-7 4-amino-2-[[(2,3-difluorophenyl)methyl]thio]-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one 
• 357612-93-2 2,4-bis[[(2,3-difluorophenyl)methyl]thio]-7(8H)-pteridinone 
• 354582-88-0 2-[[(2,3-Difluorophenyl)methyl]thio]-4,6-pyrimidinediamine 
• 261924-31-6 (2,3-difluorobenzyl) methyl sulfone 
• 654073-28-6 2-(2,3-difluoro-benzylsulfanyl)-pyrimidine-4,6-diol 
• 259100-41-9 2-Amino-5-[[(2,3-difluorophenyl)methyl]thio]thiazolo[4,5-d]pyrimidin-7(4H)-one 
• 1034355-02-6 5-chloro-N-[(2Z)-3-(2,3-difluorobenzyl)-5,5-dimethyl-1,3-thiazolidin-2-ylidene]-2-methoxybenzamide 
• 412950-73-3 5-(1-(2,3-difluorobenzylthio)-1-phenylaminomethylene)-2,2-dimethyl-[1,3]dioxane-4,6-dione 
• 412950-56-2 4-chloro-2-(2-(2,3-difluorophenyl)ethyl)quinoline 

Relevant articles and documents

NOVEL INHIBITORS

The invention relates to a compound of formula (I) or a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof, wherein R1, R2, R3, R4 and R5 are as defined herein, as inhibitors of glutaminyl cyclase (QC, EC 2.3.2.5). QC catalyzes the intramolecular cyclization of N- terminal glutamine residues into pyroglutamic acid (5-oxo-prolyl, pGlu*) under liberation of ammonia and the intramolecular cyclization of N-terminal glutamate residues into pyroglutamic acid under liberation of water.