(S)-(+)-1-Methyl-3-pyrrolidinol

(S)-(+)-1-Methyl-3-pyrrolidinol Property

Boiling point:

181-182 °C(lit.)

alpha 

6 º (c=1%, chloroform)

Density 

0.993 g/mL at 25 °C(lit.)

refractive index 

n20/D 1.4660(lit.)

Flash point:

192 °F

storage temp. 

Keep in dark place,Sealed in dry,Room Temperature

form 

Liquid

pka

14.95±0.20(Predicted)

color 

Colorless to yellow to brown

optical activity

[α]20/D +6°, c = 1 in chloroform

Sensitive 

Air Sensitive & Hygroscopic

BRN 

4349394

CAS DataBase Reference

104641-59-0(CAS DataBase Reference)

Safety

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-36

RIDADR 

NA 1993 / PGIII

WGK Germany 

3

RTECS 

TM9570000

HS Code 

29339900

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H227Combustible liquid

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P403+P235Store in a well-ventilated place. Keep cool.

(S)-(+)-1-Methyl-3-pyrrolidinol Chemical Properties,Usage,Production

Uses

(S)-1-Methyl-3-pyrrolidinol is a useful synthetic intermediate. It is used to prepare diaryl acylaminopyrimidines as adenosine A2A antagonists. It is also used to synthesize (alkoxyamino)(pyridinylamino)pyrazinecarbonitriles as selective checkpoint kinase 1 (CHK1) inhibitors with oral antitumor activities.

Uses

(S)-1-Methyl-3-pyrrolidinol is a useful synthetic intermediate. It is used to prepare diaryl acylaminopyrimidines as adenosine A2A antagonists. It is also used to synthesize (alkoxyamino)(pyridinylamino)pyrazinecarbonitriles as selective checkpoint kinase 1 (CHK1) inhibitors with oral antitumor activities.

Synthesis

The general procedure for synthesizing (S)-(+)-1-methyl-3-hydroxypyrrolidine from the compound (CAS:1104643-24-4) was as follows: 112 g of S-3-tert-butoxy-N-methylpyrrolidine was dissolved in 300 mL of dichloroethane. Subsequently, 117 g of concentrated hydrochloric acid (1.16 mol) was slowly added dropwise to the above solution and the dropwise process lasted for 1 hour. The reaction solution was stirred at 55-60°C for 2 hours. After completion of the reaction, the mixture was cooled to room temperature and diluted by adding 50 g of water. After separation of the organic layer, the aqueous layer was concentrated under reduced pressure. To the concentrated residue, 500 mL of isopropanol was added, followed by the slow addition of 46.83 g (1.16 mol) of sodium hydroxide, the addition process lasted for 1 hr, followed by stirring for 5 hr at room temperature. The solid phase inorganic material was removed by filtration and the filtrate was concentrated under reduced pressure to give a final 45.3 g of S-1-methyl-3-pyrrolidinol (total two-step yield of 58%, chemical purity of 99.36%, optical purity of 99.31% ee). The product was characterized by 1H NMR (CDCl3, 400 MHz): δ 1.73 (m, 1H), 2.20 (m, 2H), 2.34 (s, 3H), 2.47 (dd, J = 5.2,10 Hz, 1H), 2.64 (d, J = 10 Hz, 1H), 2.85 (m, 1H), 4.32 (m, 1H) ppm.

References

[1] Patent: WO2009/11551, 2009, A2. Location in patent: Page/Page column 15