trans-3,4-Difluorocinnamic acid Chemical Properties

Melting point:

194-196 °C(lit.)

Boiling point:

281.3±25.0 °C(Predicted)

Density 

1.3056 (estimate)

storage temp. 

2-8°C

solubility 

soluble in Methanol

form 

powder to crystal

pka

4.27±0.10(Predicted)

color 

White to Almost white

BRN 

7370322

CAS DataBase Reference

112897-97-9(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-36-37/39

WGK Germany 

3

HazardClass 

IRRITANT

HS Code 

29163990

MSDS

• Language:English Provider:SigmaAldrich
• Language:English Provider:ACROS
• Language:English Provider:ALFA

trans-3,4-Difluorocinnamic acid Usage And Synthesis

Chemical Properties

white to light yellow crystal powder

Uses

trans-3,4-Difluorocinnamic Acid is a starting material in the preparation of Ticagrelor (T437700), which is the first reversible oral P2Y12 receptor antagonist, provides faster, greater, and more consistent ADP-receptor inhibition than Clopidogrel.

Synthesis

GENERAL METHOD: 3,4-difluorobenzaldehyde (10 mmol), malonic acid (30 mmol, 3.12 g) and piperidine (0.5 mL) were dissolved in pyridine (20 mL) and the reaction mixture was heated to reflux for 4 hours. Upon completion of the reaction, the solution was cooled to room temperature and slowly poured into pre-cooled aqueous 3 M HCl solution (100 mL). The precipitated white solid was collected by filtration and washed sequentially with deionized water (350 mL), 5% w/v aqueous NaHCO3 solution (20 mL) and deionized water (250 mL). The resulting solid was dried in an oven at 60 °C. If necessary, the crude product can be purified by recrystallization using a solvent mixture of EtOH/H2O.4.3.1. (E)-3-(3,4-difluorophenyl)acrylic acid (2j). Yield: 1.70 g (92%).1H NMR (DMSO-d6, 400 MHz) δ: 7.85-7.91 (m, 1H), 7.55-7.57 (m, 1H), 7.56 (d, J=16.0 Hz, 1H), 7.43-7.50 (m, 1H), 6.57 (d, J=16.0 Hz, 1H).13C NMR (DMSO-d6, 101 MHz) δ: 167.30, 150.35 (dd, 1JCF=248 Hz, 2JCF=13 Hz), 149.64 (dd, 1JCF=244 Hz, 2JCF=13 Hz), 141.64, 132.03 (dd, 3JCF=6 Hz, 4JCF=4 Hz). 125.82 (dd, 3JCF=7 Hz, 4JCF=3 Hz), 120.68, 117.88 (d, 2JCF=17 Hz), 116.65 (d, 2JCF=18 Hz).

References

[1] Tetrahedron, 2016, vol. 72, # 46, p. 7256 - 7262
[2] Molecular Crystals and Liquid Crystals, 2010, vol. 528, p. 138 - 146
[3] Chemical Biology and Drug Design, 2013, vol. 81, # 2, p. 275 - 283
[4] Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 20, p. 5726 - 5732

trans-3,4-Difluorocinnamic acid(112897-97-9)Related Product Information

• 4-(Trifluoromethyl)cinnamic acid
• 3,4-Dimethoxycinnamonitrile
• Ethyl cinnamate
• Methyl cinnamate
• Cinnamic acid
• Octyl 4-methoxycinnamate
• 4-Bromocinnamic acid
• Caffeic acid
• trans-2-(3,4-difluorophenyl) cyclopropanecarboxylic acid
• ((3,4-difluorophenyl) ethynyl)triMethylsilane
• 1,3-bis(cis-2-(3,4-difluorophenyl) cyclopropyl)urea
• 3-(3,4-difluorophenyl)prop-2-yn-1-ol
• ethyCyclopropanamine, 2-(3,4-difluorophenyl)-, (1R,2S)- (REACH)
• (E)-Methyl 3-(3,4-difluorophenyl)acrylate
• trans-Methyl 2-(3,4-difluorophenyl) cyclopropanecarboxylate
• (Z)-3-(3,4-difluorophenyl) prop-2-en-1-ol
• trans-2-(3,4-difluorophenyl) cyclopropanaMine
• (1R,2S)-2-(3,4-Difluorophenyl)cyclopropanamine (2R)-Hydroxy(phenyl)ethanoate