(R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethanol Chemical Properties

Melting point:

53-58℃

Boiling point:

175.8±35.0 °C(Predicted)

Density 

1.376±0.06 g/cm3(Predicted)

storage temp. 

-20°C Freezer

solubility 

Acetonitrile (Slightly), Chloroform (Slightly)

pka

13.99±0.20(Predicted)

form 

Powder

color 

White

optical activity

[α]/D +27±1°, c = 1 in acetonitrile

λmax

272nm(MeOH)(lit.)

InChI

InChI=1/C10H8F6O/c1-5(17)6-2-7(9(11,12)13)4-8(3-6)10(14,15)16/h2-5,17H,1H3/t5-/s3

InChIKey

MMSCIQKQJVBPIR-RXMQYKEDSA-N

SMILES

C(C1C=C([C@H](O)C)C=C(C(F)(F)F)C=1)(F)(F)F |&1:4,r|

CAS DataBase Reference

127852-28-2(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xi,Xn

Risk Statements 

36/37/38-52/53-22

Safety Statements 

26-36/37/39-61

WGK Germany 

3

Hazard Note 

Irritant

HS Code 

29062990

(R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethanol Usage And Synthesis

Uses

(R)-[3,5-bis (trifluoromethyl) phenyl] ethanol is an important chiral intermediate for the synthesis of novel chemotherapeutic and antiemetic drugs NK-1 receptor antagonists. Antidepressants have good potential efficacy in treating a range of central and peripheral nervous system depressions.

Preparation

At present, the methods for preparing optically pure (R)-[3,5-bis (trifluoromethyl) phenyl] ethanol include chemical methods and biological methods. Chemical synthesis requires the use of expensive transition metal Ru and other chemical catalysts, complicated steps, harsh reaction conditions, high energy consumption, large pollution, and low yield. Biological law is the use of free enzymes or whole cells for catalytic preparation. It has the characteristics of mild reaction conditions, high catalytic efficiency, and strong specificity.

Chemical Properties

White fine crystalline powder

Uses

(R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethanol is an intermediate in the synthesis of Aprepitant (A729800), a novel selective neurokinin-1 (NK-1) receptor antagonist. In vitro studies using human liver microsomes indicate that Aprepitant is metabolised primarily by CYP3A4 with minor metabolism by CYP1A2 and CYP2C19, and no metabolism by CYP2D6, CYP2C9, or CYP2E1. Antiemetic.

General Description

(R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethanol is a key intermediate for the synthesis of aprepitant, a potent human neurokinin-1 (NK-1) receptor.

Synthesis

The general procedure for the synthesis of 1-[3,5-bis(trifluoromethyl)phenyl]ethanol from 3,5-bis(trifluoromethyl)phenylacetophenone and cis-1-amino-2,3-dihydro-1H-inden-2-ol was as follows: in Example 5, [RuCl2(p-cymene)]2 (18.4 g), (1S,2R)- cis-1-amino-2-inden-2-ol (9.0 g) and 1- (3,5-bis(trifluoromethyl)phenyl)ethan-1-one (3 kg) were dissolved in 2-propanol (21 L), stirred for 30 min and thoroughly degassed under vacuum. A 5M sodium hydroxide solution (28mL) was then added and the mixture was aged for 4-6 hours to ensure complete conversion of the feedstock. Upon completion of the reaction, the mixture was poured into 1N HCl (21L) and extracted with heptane (2 x 10.5L). The organic layers were combined, washed with brine, and 1,4-diazabicyclo[2.2.2]octane (740 g) was added. The solution was concentrated to nearly 4 mL/g of alcohol (KF < 200 μg/mL; 2-propanol < 5 vol%). The mixture was inoculated at 40°C and allowed to cool slowly to room temperature to form crystalline species, which were then further cooled to 0°C. The crystalline product was collected by filtration, washed with cold heptane and dried to give the DABCO complex in 75-80% yield and ee value >99%.

References

[1] Patent: US2002/22725, 2002, A1
[2] Patent: US2002/52493, 2002, A1
[3] Patent: US2002/52494, 2002, A1
[4] Patent: US6432952, 2002, B1
[5] Patent: US2003/215456, 2003, A1

(R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethanol(127852-28-2)Related Product Information

• 2-AMINO-1-PHENYLETHANOL
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• Chlorodimethylphenylsilane
• Phenyl salicylate
• Ethanol
• Silicone oil (high temperature)
• N-Methyldiethanolamine
• Ethyl acetate
• PHENYL VALERATE
• 2-Methylaminoethanol
• Phenethyl alcohol
• PHENYL RESIN
• methylphenyl silicone resin
• 2-(R)-[1-(R)-(3,5-Bis(trifluoromethyl)phenyl)ethoxy]-3-(S)-fluorophenylmorpholine
• 2-[3,5-Bis(trifluoromethyl)phenyl]propan-2-ol
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• (S)-1-[3,5-BIS(TRIFLUOROMETHYL)PHENYL]ETHANOL,(1R)-1-[3,5-BIS(TRIFLUOROMETHYL)PHENYL]ETHANOL
• Aprepitant