N-(tert-Butoxycarbonyl)-(3S)-hydroxy-L-proline methyl ester Chemical Properties

Boiling point:

335.2±42.0 °C(Predicted)

Density 

1.216

storage temp. 

2-8°C

pka

14.03±0.40(Predicted)

Appearance

Light yellow to yellow Viscous liquid

InChI

InChI=1S/C11H19NO5/c1-11(2,3)17-10(15)12-6-5-7(13)8(12)9(14)16-4/h7-8,13H,5-6H2,1-4H3/t7-,8-/m0/s1

InChIKey

SVSSZFBZFUSINI-YUMQZZPRSA-N

SMILES

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

N-(tert-Butoxycarbonyl)-(3S)-hydroxy-L-proline methyl ester Usage And Synthesis

Uses

(2S,3S)-3-Hydroxy-1,2-pyrrolidinedicarboxylic acid 1-tert-butyl 2-methyl ester is a reactant used to improve potency of imidazo[1,2-b]pyridazines as IKKβ inhibitors.

Synthesis

GENERAL STEPS: A solution of DMF (100 mL) containing N-Boc-(2S,3S)-3-hydroxy-2-carboxypyrrolidine (37.16 g, 71 mmol) was cooled to 0°C. To this solution was added K2CO3 (16 g, 116 mmol) followed by slow dropwise addition of iodomethane (5.4 mL, 87 mmol). The reaction mixture was gradually warmed to room temperature over a period of 1 h. It was observed that the solution changed to a yellow non-homogeneous mixture. Next, the mixture was heated at 90 °C for 1 h, after which it was cooled to room temperature. After completion of the reaction, the reaction solution was diluted with saturated brine and extracted with ether. The organic phases were combined, dried with anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford the target product (2S,3S)-1-(tert-butoxycarbonyl)-3-hydroxy-pyrrolidine-2-carboxylic acid methyl ester (14.8 g, 87% yield) as a yellow oil.

References

[1] Patent: US2008/20986, 2008, A1. Location in patent: Page/Page column 16
[2] Patent: WO2009/94287, 2009, A1. Location in patent: Page/Page column 31
[3] Patent: WO2010/138496, 2010, A1. Location in patent: Page/Page column 38-39
[4] Patent: WO2011/68926, 2011, A1. Location in patent: Page/Page column 39-40
[5] Patent: WO2010/33531, 2010, A1. Location in patent: Page/Page column 66