(S)-3-HYDROXYMETHYL-PYRROLIDINE-1-CARBOXYLIC ACID TERT-BUTYL ESTER

(S)-3-HYDROXYMETHYL-PYRROLIDINE-1-CARBOXYLIC ACID TERT-BUTYL ESTER Property

Boiling point:

285-289℃

Density 

1.084

storage temp. 

2-8°C

form 

liquid

pka

14.93±0.10(Predicted)

color 

Brown

Water Solubility 

Slightly soluble in water.

InChI

InChI=1S/C10H19NO3/c1-10(2,3)14-9(13)11-5-4-8(6-11)7-12/h8,12H,4-7H2,1-3H3/t8-/m0/s1

InChIKey

HKIGXXRMJFUUKV-QMMMGPOBSA-N

SMILES

N1(C(OC(C)(C)C)=O)CC[C@H](CO)C1

CAS DataBase Reference

199174-24-8

Safety

HazardClass 

IRRITANT

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.

(S)-3-HYDROXYMETHYL-PYRROLIDINE-1-CARBOXYLIC ACID TERT-BUTYL ESTER Chemical Properties,Usage,Production

Uses

It is used as a pharmaceutical intermediate.

Synthesis

The general procedure for the synthesis of (S)-1-BOC-3-hydroxymethylpyrrolidine from di-tert-butyl dicarbonate and compound (CAS:1264942-79-1) was as follows: 1. 1-[(1S)-1'-phenylethyl]pyrrolidine (8.81 g, 27.6 mmol) was dissolved in 1,2-dichloroethane (75 ml) at room temperature and 1-chloroethyl chloroformate (8.1 ml, 75 mmol) was added to this solution. 2. The resulting mixture was refluxed for 5 hours and then cooled to room temperature. 3. diisopropylethylamine (2.3 ml, 13 mmol) was added to the cooled brown solution and the mixture was refluxed again for 3 hours. 4. After completion of the reaction, the mixture was concentrated and the residue was diluted with ethyl acetate and washed with 1N aqueous hydrochloric acid. 5. The organic layer was dried with anhydrous sodium sulfate and subsequently concentrated under reduced pressure. 6. The residue was dissolved in methanol, an aqueous 1N hydrochloric acid solution was added and the aqueous solution was washed with ethyl acetate. 7. The aqueous solution was alkalized with solid potassium carbonate and the alkaline solution was cooled to 0 °C. 8. tert-Butyl dicarbonate (6.3 g, 29 mmol) was added to tetrahydrofuran (75 ml) at 0 °C. 9. The resulting mixture was stirred for 3 hours and then the organic material was extracted with ethyl acetate. 10. The organic layer was dried with anhydrous sodium sulfate and the solvent was removed under reduced pressure. 11. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate = 3/1 to 1/2) to afford tert-butyl 3-hydroxymethylpyrrolidine-1-carboxylate (2.96 g, 14.7 mmol, 53%) as a colorless oil.

References

[1] Patent: WO2011/19090, 2011, A1. Location in patent: Page/Page column 45-46