L-Proline, 4,4-difluoro- (9CI)

L-Proline, 4,4-difluoro- (9CI) Property

Boiling point:

254.0±40.0 °C(Predicted)

Density 

1.41±0.1 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2–8 °C

pka

1.40±0.40(Predicted)

Appearance

White to off-white Solid

Safety

HS Code 

2933998090

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.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P271Use only outdoors or in a well-ventilated area.

P280Wear protective gloves/protective clothing/eye protection/face protection.

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.

P312Call a POISON CENTER or doctor/physician if you feel unwell.

P321Specific treatment (see … on this label).

P330Rinse mouth.

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P337+P313IF eye irritation persists: Get medical advice/attention.

P362Take off contaminated clothing and wash before reuse.

P403+P233Store in a well-ventilated place. Keep container tightly closed.

P405Store locked up.

P501Dispose of contents/container to..…

L-Proline, 4,4-difluoro- (9CI) Chemical Properties,Usage,Production

Synthesis

General procedure for the synthesis of (S)-4,4-difluoropyrrolidine-2-carboxylic acid from N-Boc-4,4-difluoro-L-proline: 1. (S)-1-(tert-butoxycarbonyl)-4,4-difluoropyrrolidine-2-carboxylic acid (500 mg, 1.99 mmol) was dissolved in methanol (30 mL). 2. To the above solution was added a dioxane solution (3 mL) of 4N HCl. 3. The reaction mixture was stirred at room temperature for 6 hours. 4. Upon completion of the reaction, the reaction solution was concentrated to give an oily product (480 mg, 100% yield), which could be used in the next step without further purification. 5. The structure of the product was determined by 1H NCl and the reaction was carried out in aqueous solution. 5. The structure of the product was confirmed by 1H NMR (CD3OD, 400 MHz): δ 4.76 (1H, t, J = 8.5 Hz), 3.79-3.87 (2H, m), 2.91-3.03 (1H, m), 2.73-2.82 (1H, m).

References

[1] Patent: US2008/9497, 2008, A1. Location in patent: Page/Page column 109
[2] Patent: WO2014/82379, 2014, A1. Location in patent: Page/Page column 158; 159; 163
[3] Tetrahedron Letters, 1998, vol. 39, # 10, p. 1169 - 1172