2-(Hydroxymethyl)pyrrolidine

2-(Hydroxymethyl)pyrrolidine Property

Boiling point:

98 °C / 14mmHg

Density 

1.04

refractive index 

1.4840

storage temp. 

Keep in dark place,Sealed in dry,Room Temperature

solubility 

Soluble in ethanol.

pka

14.77±0.10(Predicted)

form 

clear liquid

color 

Colorless to Light orange to Yellow

optical activity

Consistent with structure

Safety

HS Code 

2933998090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

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

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

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

P405Store locked up.

2-(Hydroxymethyl)pyrrolidine Chemical Properties,Usage,Production

Uses

rac-Prolinol is an intermediate in the synthesis of Physostigmine and Physostigmine derivative used for treatment of Alzheimer''s disease.

Uses

2-(Hydroxymethyl)pyrrolidine is an intermediate in the synthesis of Physostigmine and Physostigmine derivative used for treatment of Alzheimer's disease.

Definition

2-(Hydroxymethyl)pyrrolidine is an amino alcohol formed by reduction of the amino acid proline.

Synthesis

General procedure for the synthesis of pyrrolidine-2-methanol from DL-proline: DL-proline (6.0 g, 52.0 mmol) was slowly added in batches to a THF (80 mL) suspension of LiAlH4 (3.0 g, 78.0 mmol) under stirring at 0 °C and nitrogen protection, and the addition process was controlled to be completed within 30 min. The reaction mixture was gradually warmed up to room temperature and then continued to be heated and refluxed for 3 hours. Upon completion of the reaction, a 20% KOH solution (18-20 mL) was slowly added at 0 °C to quench the reaction. The mixture was filtered through a Celite pad and the filter cake was washed with THF. The solid obtained by filtration was again mixed with THF and filtered at reflux for 30 min. All the filtrates were combined and concentrated to give the light yellow liquid product K1 (3.2 g, 65% yield), which gradually transformed to a dark brown liquid during storage. The Rf value of the product was 0.1 (unfolding agent: DCM solution of 10% MeOH containing 1 drop of AcOH, ninhydrin color developed).

References

[1] Tetrahedron, 2010, vol. 66, # 40, p. 7970 - 7974
[2] Patent: WO2015/181676, 2015, A1. Location in patent: Page/Page column 166-167
[3] Patent: WO2011/22508, 2011, A2. Location in patent: Page/Page column 59
[4] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1931, vol. 203, p. 279,285
[5] Monatshefte fuer Chemie, 1952, vol. 83, p. 541