3-Chloro-4-(3-fluorobenzyloxy)aniline Chemical Properties

Melting point:

78.0 to 82.0 °C

Boiling point:

387.9±32.0 °C(Predicted)

Density 

1.306±0.06 g/cm3(Predicted)

storage temp. 

Keep in dark place,Inert atmosphere,Room temperature

solubility 

Acetonitrile (Slightly), DMSO (Slightly), Methanol

form 

powder to crystal

pka

3.98±0.10(Predicted)

color 

White to Gray to Red

InChI

InChI=1S/C13H11ClFNO/c14-12-7-11(16)4-5-13(12)17-8-9-2-1-3-10(15)6-9/h1-7H,8,16H2

InChIKey

AYPFEYDGZDPAPE-UHFFFAOYSA-N

SMILES

C1(N)=CC=C(OCC2=CC=CC(F)=C2)C(Cl)=C1

Safety Information

RIDADR 

3077

HazardClass 

9

PackingGroup 

III

HS Code 

29221990

3-Chloro-4-(3-fluorobenzyloxy)aniline Usage And Synthesis

Chemical Properties

Tan Solid

Uses

3-Chloro-4-(3-fluorobenzyloxy)aniline is an intermediate in the synthesis of Lapatinib (L175800).

Synthesis

Example 5: Preparation of 3-chloro-4-(3-fluorobenzyloxy)aniline In a 1 L reactor, 35.6 g of Intermediate-A (3-chloro-4-(3-fluorobenzyloxy)nitrobenzene), 21.2 g of iron powder (70 mesh), and 60.9 g of ammonium chloride were dissolved in a solvent mixture of 506 mL of ethanol and 128 mL of water, and the reaction was carried out at reflux for 2 hours. Upon completion of the reaction, the reaction mixture was cooled to 20-25 °C and the insoluble iron oxide was removed by vacuum filtration. The solid obtained by filtration was washed with ethanol. The filtrates were combined and the solvent was removed by evaporation to give 94.9 g of a highly moist orange solid. The solid was mixed with 400 mL of dichloromethane to dissolve the organic product. The turbid solution was filtered to remove inorganic salts. The filtrate was transferred to a partition funnel to separate the organic phase and remove the aqueous residue. The organic phase was dried over anhydrous sodium sulfate and evaporated to dryness to give 30.8 g of 3-chloro-4-(3-fluorobenzyloxy)aniline (Yield: 96%, Purity as determined by HPLC: 99.67%, Major impurity content: 0.10%).

References

[1] Patent: US2004/53946, 2004, A1
[2] Patent: US2015/366868, 2015, A1. Location in patent: Paragraph 0158
[3] Journal of Medicinal Chemistry, 2015, vol. 58, # 14, p. 5522 - 5537
[4] Patent: WO2009/33581, 2009, A1. Location in patent: Page/Page column 59-60
[5] Patent: WO2009/63054, 2009, A1. Location in patent: Page/Page column 68-69

3-Chloro-4-(3-fluorobenzyloxy)aniline(202197-26-0)Related Product Information

• Acid Blue 93
• alpha-Chloro-o-fluorotoluene
• Aniline
• 4-(Trifluoromethoxy)aniline
• 4-Methoxybenzylchloride
• 2-(Trifluoromethyl)benzyl chloride
• p-Anisidine
• o-Anisidine
• m-Anisidine
• (Trifluoromethoxy)benzene
• 5-[4-((3-Chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)quinazolin-6-yl]-2-furaldehyde
• Lapatinib iMpurity
• Lapatinib Impurity 16
• O-De(3-fluorobenzyl) Lapatinib
• Lapatinib impurity L
• Lapatinib 4-Fluoro Impurity
• N-De[2-(Methylsulfonyl)ethyl] Lapatinib
• Lapatinib IMpurity 8