N-BOC-cis-4-fluoro-L-proline Chemical Properties

Melting point:

157-161.°C

Boiling point:

346.0±42.0 °C(Predicted)

Density 

1.24±0.1 g/cm3(Predicted)

refractive index 

-57 ° (C=1, MeOH)

storage temp. 

Keep in dark place,Sealed in dry,Room Temperature

form 

powder to crystal

pka

3.53±0.40(Predicted)

color 

White to Almost white

optical activity

[α]22/D 71.0±5°, c = 1 in chloroform

InChI

InChI=1S/C10H16FNO4/c1-10(2,3)16-9(15)12-5-6(11)4-7(12)8(13)14/h6-7H,4-5H2,1-3H3,(H,13,14)/t6-,7-/m0/s1

InChIKey

YGWZXQOYEBWUTH-BQBZGAKWSA-N

SMILES

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

CAS DataBase Reference

203866-13-1(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26

WGK Germany 

3

HazardClass 

IRRITANT

HS Code 

29339900

N-BOC-cis-4-fluoro-L-proline Usage And Synthesis

Chemical Properties

White powder

Uses

N-Boc-cis-4-fluoro-L-proline can be used as a substrate in the preparation of:

• α4β2 Receptor ligands bearing pyrrolidine nucleus.
• β-Amino pyrrolidine-2-carbonitrile derivatives as possible dipeptidyl peptidase IV (DPP4) inhibitors.

Synthesis

General procedure for the synthesis of (2S,4S)-4-fluoro-1-tert-butoxycarbonylpyrrolidine-2-carboxylic acid from N-tert-butoxycarbonyl-cis-4-fluoro-L-proline methyl ester: To a solution of N-tert-butoxycarbonyl-cis-4-fluoro-L-proline methyl ester (5.83 g, 23.58 mmol) in tetrahydrofuran (THF, 30 mL) was added, at 0 °C, lithium hydroxide (LiOH, 1.98 g) in aqueous solution (30 mL). The reaction mixture was stirred at room temperature for 2 h. The pH was subsequently adjusted to 5 with dilute hydrochloric acid (1 M). After evaporating THF under reduced pressure, the pH of the aqueous layer was adjusted to 2 with dilute hydrochloric acid (1 M) and extracted with ethyl acetate (EtOAc, 80 mL x 3). The organic layers were combined, dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure to afford (2S,4S)-4-fluoro-1-tert-butoxycarbonylpyrrolidine-2-carboxylic acid as a white solid (5.3 g, 96% yield). The structure of the compound was confirmed by the following spectral data: mass spectrum (ESI, positive ion mode) m/z: 234.24 [M + H]+; NMR hydrogen spectrum (400 MHz, CDCl3) δ (ppm): 8.76 (broad single peak, 1H), 5.28-5.12 (multiple peaks, 1H), 4.56-4.44 (multiple peaks, 1H), 3.86- 3.58 (multiple peaks, 2H), 2.77-2.01 (multiple peaks, 2H), 1.48-1.44 (double peaks, 9H, J = 16 Hz).

References

[1] Patent: WO2014/19344, 2014, A1. Location in patent: Paragraph 00435
[2] Patent: WO2014/82380, 2014, A1. Location in patent: Paragraph 00403; 00405
[3] Patent: WO2014/82379, 2014, A1. Location in patent: Page/Page column 144; 145
[4] Patent: WO2014/131315, 2014, A1. Location in patent: Page/Page column 144
[5] Patent: US2015/79028, 2015, A1. Location in patent: Paragraph 1061; 1066; 1067; 1068; 1069

N-BOC-cis-4-fluoro-L-proline(203866-13-1)Related Product Information

• BOC-L-Proline
• N-Methyl-2-pyrrolidone
• Polyvinylpyrrolidone
• Pyrrolidine
• cis-4-Hydroxy-L-proline
• tert-Butyl carbazate
• Povidone iodine
• tert-Butanol
• L-PROLINE-(4-3H(N))
• D-Proline
• Ascoric Acid
• N-Boc-(2R,3R,4S)-dolaproine
• TERT-BUTYL N-(2-HYDROXYETHYL)CARBAMATE
• N-Boc-4-piperidinemethanol
• N-Boc-endo-3-aminotropane
• N-Boc-exo-3-aminotropane
• N-Boc-pyrroline
• N-Boc-3-piperidineacetic acid