Z-CIS-HYP-OH

Z-CIS-HYP-OH Property

Boiling point:

486.9±45.0 °C(Predicted)

Density 

1.416±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

pka

3.78±0.40(Predicted)

Appearance

White to off-white Solid

optical activity

-37.8°(C=0.01g/ml MEOH)

Safety

HazardClass 

IRRITANT

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

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

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

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

Z-CIS-HYP-OH Chemical Properties,Usage,Production

Synthesis

General procedure for the synthesis of (2S,4S)-N-Cbz-4-hydroxypyrrolidine-2-carboxylic acid from (2S,4R)-Cbz-4-methanesulfonyloxyproline methyl ester: firstly, 708 g of water and 337 g of 48% sodium hydroxide solution were added to 928 g of the crude product obtained by reference to Example 3. The temperature of the mixture was raised to 80°C and the reaction was ripened at this temperature for 3 hours. Upon completion of the maturation, the temperature was kept constant and 146 g of solvent was distilled under reduced pressure until the pressure was reduced to 13 kPa. Subsequently, the mixture was cooled to 20°C, 180 g of 48% sodium hydroxide solution was added and aged at 25°C for 12 hours. The amount of cis-Benzyloxycarbonyl-4-hydroxy-L-proline in the reaction solution was determined by analysis to be 2.19 mol (81.0% yield based on trans-4-hydroxy-L-proline). Next, 35 g of toluene was added to the hydrolysis reaction solution and the mixture was concentrated under reduced pressure at 7 kPa and 40 °C to distill 332 g of solvent. Then, 161 g of concentrated sulfuric acid was added dropwise to the concentrated solution and the pH was adjusted to 1.3. After acidic adjustment, 710 g of tetrahydrofuran and 354 g of water were added for layered separation. To the separated water layer, 356 g of tetrahydrofuran was added and the separation was performed again. All the separated tetrahydrofuran layers were combined and concentrated at 40 °C under reduced pressure at 26 kPa, resulting in 896 g of concentrate containing 2.12 mol of cis-Benzyloxycarbonyl-4-hydroxy-L-proline (90.2% yield) with a cis/trans ratio of 98.3/1.7.

References

[1] Patent: JP5703654, 2015, B2. Location in patent: Paragraph 0054; 0055