N-Boc-4-oxo-L-proline

N-Boc-4-oxo-L-proline Property

Melting point:

160 °C (dec.)

alpha 

1 º (c=1 in chloroform)

Boiling point:

390.8±42.0 °C(Predicted)

Density 

1.304±0.06 g/cm3(Predicted)

vapor pressure 

0.001Pa at 25℃

storage temp. 

Inert atmosphere,2-8°C

form 

Solid:crystalline

pka

3.85±0.20(Predicted)

color 

White to Almost white

optical activity

[α]22/D +19.0 to +23.0°, c = 0.5 in acetone

Water Solubility 

Insoluble in water.

InChI

InChI=1S/C10H15NO5/c1-10(2,3)16-9(15)11-5-6(12)4-7(11)8(13)14/h7H,4-5H2,1-3H3,(H,13,14)/t7-/m0/s1

InChIKey

CKYGSXRXTIKGAJ-ZETCQYMHSA-N

SMILES

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

LogP

0.49

CAS DataBase Reference

84348-37-8(CAS DataBase Reference)

Safety

Hazard Codes 

Xn

Risk Statements 

22-36

Safety Statements 

26

WGK Germany 

3

HS Code 

29339900

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H301Toxic if swalloed

H302Harmful if swallowed

H319Causes serious eye irritation

Precautionary statements

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

P321Specific treatment (see … on this label).

P405Store locked up.

N-Boc-4-oxo-L-proline Chemical Properties,Usage,Production

Chemical Properties

white to off-white solid

Uses

N-Boc-4-oxo-L-proline is used in practical Synthesis of Boc-Protected cis-4-Trifluoromethyl and cis-4-Difluoromethyl-l- prolines.

Definition

ChEBI: Boc-L-Pro(4-oxo) is a proline derivative.

Synthesis

General procedure for the synthesis of (S)-1-(tert-butoxycarbonyl)-4-oxopyrrolidine-2-carboxylic acid from Boc-L-hydroxyproline: trichloroisocyanuric acid (75.6 g) was added to a solution (1000 mL) of ethyl acetate of (4R)-1-(tert-butoxycarbonyl)-4-hydroxy-L-proline (Formula IV, prepared according to the method of Example 1; 100 g). The reaction system was cooled to 0°C to -5°C. An ethyl acetate solution of TEMPO (3.38 g, dissolved in 50 mL of ethyl acetate) was slowly added at -5°C to 10°C and the reaction mixture was stirred at the same temperature for 20 minutes. Subsequently, the reaction system was warmed up to 25 °C to 30 °C and kept at this temperature and stirred for 60 min. Upon completion of the reaction, the reaction was quenched with deionized water (200 mL) and stirring was continued at 25°C to 30°C for 60 minutes. The reaction mixture was filtered through a Hyflo? bed. The filtrate was washed with deionized water (2 x 200 mL) and partitioned. The organic layer was washed with aqueous sodium chloride (prepared from 40 g sodium hydroxide dissolved in 200 mL of deionized water). The organic layer was concentrated under reduced pressure at about 50°C to give a residue. The residue was dissolved in ethyl acetate (100 mL) and hexane (400 mL) was slowly added. The reaction mixture was stirred at 25 °C to 30 °C for 30 min and filtered, and the resulting solid was washed with a mixture of ethyl acetate (20 mL) and hexane (80 mL) and dried under reduced pressure at 40 °C to 45 °C to give 1-(tert-butoxycarbonyl)-4-oxo-L-proline. Yield: 95.9%.

References

[1] Patent: WO2015/19238, 2015, A1. Location in patent: Page/Page column 9
[2] Journal of the American Chemical Society, 2017, vol. 139, # 17, p. 6152 - 6159
[3] Organic Process Research and Development, 2015, vol. 19, # 1, p. 270 - 283
[4] Patent: WO2004/5249, 2004, A1. Location in patent: Page 30-31
[5] Tetrahedron Letters, 1993, vol. 34, # 46, p. 7489 - 7492