N-Boc-4,4-difluoro-L-proline methyl ester

N-Boc-4,4-difluoro-L-proline methyl ester Property

Melting point:

41-46 °C

Boiling point:

293℃

Density 

1.22

Flash point:

110 °C

storage temp. 

2-8°C

pka

-8.00±0.60(Predicted)

form 

White to off-white crystalline powder

Appearance

White to light yellow Solid

InChI

InChI=1S/C11H17F2NO4/c1-10(2,3)18-9(16)14-6-11(12,13)5-7(14)8(15)17-4/h7H,5-6H2,1-4H3/t7-/m0/s1

InChIKey

RQDZKOOUQIDZOG-ZETCQYMHSA-N

SMILES

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

Safety

WGK Germany 

3

HS Code 

29339900

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.

N-Boc-4,4-difluoro-L-proline methyl ester Chemical Properties,Usage,Production

Uses

peptide synthesis

reaction suitability

reaction type: Boc solid-phase peptide synthesis

Synthesis

General procedure for the synthesis of N-BOC-4,4-difluoro-L-proline methyl ester from BOC-4-oxo-L-proline methyl ester: Intermediate 5a (300 g, 1.23 mmol, 1.00 eq.) was dissolved in dichloromethane (30 mL) at 0 °C, and DAST (1.80 g, 11.2 mmol, 9.00 eq.) was slowly added dropwise to the dichloromethane (10 mL) solution. The reaction mixture was stirred overnight at room temperature. Upon completion of the reaction, the reaction mixture was washed sequentially with saturated aqueous sodium bicarbonate solution (1 x 30 mL) and brine (3 x 30 mL). The organic layer was separated, dried with anhydrous sodium sulfate and concentrated under reduced pressure to give Intermediate 5b (300 mg, 92% yield) as a yellow oil.

References

[1] Patent: WO2006/123257, 2006, A2. Location in patent: Page/Page column 70
[2] Patent: WO2013/96771, 2013, A1. Location in patent: Page/Page column 95
[3] Journal of the American Chemical Society, 2016, vol. 138, # 7, p. 2443 - 2453
[4] Journal of Medicinal Chemistry, 2018, vol. 61, # 17, p. 7589 - 7613
[5] Patent: WO2005/23762, 2005, A1. Location in patent: Page/Page column 72