(3R)-(+)-1-BENZYL-3-(TERT-BUTOXYCARBONYLAMINO)PYRROLIDINE

(3R)-(+)-1-BENZYL-3-(TERT-BUTOXYCARBONYLAMINO)PYRROLIDINE Property

Melting point:

77-81 °C(lit.)

Boiling point:

385.1±31.0 °C(Predicted)

Density 

1.08

refractive index 

18.5 ° (C=2, EtOH)

storage temp. 

2-8°C

solubility 

almost transparency in Methanol

form 

powder to crystal

pka

12.31±0.20(Predicted)

color 

White to Almost white

optical activity

[α]20/D +6°, c = 1% in chloroform

CAS DataBase Reference

131878-23-4(CAS DataBase Reference)

Safety

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-36

WGK Germany 

3

HS Code 

29339900

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H315Causes skin irritation

H318Causes serious eye damage

H335May cause respiratory irritation

Precautionary statements

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

P280Wear protective gloves/protective clothing/eye protection/face protection.

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

(3R)-(+)-1-BENZYL-3-(TERT-BUTOXYCARBONYLAMINO)PYRROLIDINE Chemical Properties,Usage,Production

Synthesis

The general procedure for the synthesis of (R)-1-benzyl-3-(tert-butoxycarbonylamino)pyrrolidine from di-tert-butyl dicarbonate and (R)-1-benzyl-3-amino pyrrolidine was as follows: first, sodium bicarbonate (5.92 g, 70.5 mmol) was dissolved in 118 mL of deionized water, and then this solution was added to a 118 mL acetonitrile solution of (R)-(+)-benzylamino pyrrolidine 1a (5.00 g, 28.4 mmol) in 118 mL of acetonitrile solution. The mixture was stirred at room temperature for 10 minutes. Subsequently, di-tert-butyl dicarbonate (6.22 g, 28.5 mmol) was added and stirring was continued overnight at room temperature. After completion of the reaction, the reaction solution was concentrated under reduced pressure and the residue was extracted three times with dichloromethane. The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by fast column chromatography (eluent ratio methanol: dichloromethane = 2:98). Finally, the solvent was removed in vacuum to afford 4.24 g of tert-butyl (R)-(1-benzylpyrrolidin-3-yl)carbamate in 65.2% yield. The product was characterized by 1H NMR (400 MHz, CDCl3): δ 7.36-7.26 (m, 5H), 4.86 (bs, 1H), 4.18 (bs, 1H), 3.61 (s, 2H), 2.79 (bs, 1H), 2.65-2.61 (m, 1H), 2.54 (d, J=8.0 Hz, 1H), 2.34- 2.25 (m, 2H), 1.61-1.51 (m, 1H), 1.46 (s, 9H). The specific optical rotation [α]D was +2.5° (c 0.620, CHCl3).

References

[1] Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 8, p. 1495 - 1510
[2] Journal of Medicinal Chemistry, 2001, vol. 44, # 11, p. 1815 - 1826
[3] Journal of Medicinal Chemistry, 2002, vol. 45, # 3, p. 721 - 739