(2S,4R)-1-Boc-2-carbamoyl-4-hydroxypyrrolidine Chemical Properties

Boiling point:

424.8±45.0 °C(Predicted)

Density 

1.262±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

pka

14.33±0.40(Predicted)

InChI

InChI=1S/C10H18N2O4/c1-10(2,3)16-9(15)12-5-6(13)4-7(12)8(11)14/h6-7,13H,4-5H2,1-3H3,(H2,11,14)/t6-,7+/m1/s1

InChIKey

ISGKNURQVBUGBO-RQJHMYQMSA-N

SMILES

N1(C(OC(C)(C)C)=O)C[C@H](O)C[C@H]1C(N)=O

(2S,4R)-1-Boc-2-carbamoyl-4-hydroxypyrrolidine Usage And Synthesis

Synthesis

General procedure for the synthesis of (2S,4R)-1-Boc-2-carbamoyl-4-hydroxypyrrolidine from Boc-L-hydroxyproline: Step 2: Preparation of tert-butyl (2S,4R)-2-carbamoyl-4-hydroxypyrrolidine-1-carboxylate (2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid 13b (86.4 g, 0.374 mol) was dissolved in 1.2 L of tetrahydrofuran and triethylamine (41 g, 0.411 mol) was added under argon protection. The reaction mixture was cooled to -15 °C and ethyl chloroformate (43.84 g, 0.411 mol) was added slowly. After stirring for 10 min, concentrated ammonia (236.8 mL) was added. The reaction mixture was slowly warmed to 5 °C over 2 h. Ammonium chloride (32 g) was subsequently added. Stirring was continued for 30 minutes followed by phase separation. The organic phase was dried with anhydrous sodium sulfate and the aqueous phase was extracted with ethyl acetate (100 mL x 2). The organic extracts were combined and concentrated under reduced pressure to afford (2S,4R)-1-Boc-2-carbamoyl-4-hydroxypyrrolidine (i.e., tert-butyl (2S,4R)-2-carbamoyl-4-hydroxypyrrolidine-1-carboxylate 13c) (74 g, 86% yield) as a white solid.

References

[1] Chemical and Pharmaceutical Bulletin, 2006, vol. 54, # 12, p. 1709 - 1714
[2] Patent: EP2246347, 2010, A1. Location in patent: Page/Page column 39
[3] Patent: WO2003/106456, 2003, A2. Location in patent: Page 28
[4] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 23, p. 6053 - 6061