Methoxycarbonyl-L-tert-leucine Chemical Properties

Melting point:

1090C

Boiling point:

320.9±25.0 °C(Predicted)

Density 

1.126±0.06 g/cm3(Predicted)

vapor pressure 

0Pa at 25℃

storage temp. 

2-8°C

solubility 

Soluble in ethyl acetate and methanol.

pka

4.46±0.10(Predicted)

form 

powder

color 

White to off-white

Water Solubility 

26.4g/L at 20℃

InChI

InChI=1S/C8H15NO4/c1-8(2,3)5(6(10)11)9-7(12)13-4/h5H,1-4H3,(H,9,12)(H,10,11)/t5-/m1/s1

InChIKey

NWPRXAIYBULIEI-RXMQYKEDSA-N

SMILES

C(O)(=O)[C@H](C(C)(C)C)NC(OC)=O

LogP

0.832 at 21℃

Safety Information

HS Code 

2933399090

Methoxycarbonyl-L-tert-leucine Usage And Synthesis

Description

Methoxycarbonyl-L-tert-leucine is a kind of amino acid deriviative. It is a very useful intermediate for efficient synthesis of the HIV protease inhibitor BMS-232632 as well as atazanavir bisulfate. 

References

Zhongmin Xu, †, et al. "Process Research and Development for an Efficient Synthesis of the HIV Protease Inhibitor BMS-232632." Organic Process Research & Development 6.3(2002):323-328.
Simhadri, Srinivas. "Process for the preparation of atazanavir bisulfate." (2016).
https://www.alfa.com/en/search/?q=14328-63-3

Chemical Properties

White Solid

Uses

The coupling of the two key intermediates, N-(methoxycarbonyl)-l-tert-leucine acylated benzyl hydrazine and chloromethyl ketone, via an S N 2 reaction furnished the amino ketone in high yield under our optimized conditions in practical synthesis of the HIV Protease Inhibitor Atazanavir via a Highly diastereoselective Reduction Approach.

Flammability and Explosibility

Not classified

Synthesis

Step 1: Synthesis of (S)-2-(methoxycarbonylamino)-3,3-dimethylbutanoic acid: (S)-2-amino-3,3-dimethylbutanoic acid (5.0 g, 38.6 mmol) was dissolved in a mixture of dioxane (20 ml) and 2N sodium hydroxide solution (62 ml, pH=8-9) at 0 °C. Methyl chloroformate (5.88 ml, 76.33 mmol) was added dropwise with stirring. The reaction mixture was warmed up to 60°C with continuous stirring for 18 hours. After completion of the reaction, the mixture was cooled to room temperature and extracted with dichloromethane (DCM) to separate the aqueous layer. The aqueous layer was acidified to acidity with 1N hydrochloric acid and then extracted with ethyl acetate (EtOAc). The organic layer was dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure to remove the solvent. The resulting crude product was stirred and distilled in hexane to give N-methoxycarbonyl-L-tert-leucine as a white solid. Yield: 8.5 g (quantitative yield). NMR hydrogen spectrum (300MHz, CDCl3): δ5.25 (d, 1H, J=10.5Hz), 4.19 (d, 1H, J=9.6Hz), 3.70 (s, 3H), 1.03 (s, 9H). Mass spectrum: [M-1]- 188 (100%). IR spectrum (potassium bromide pressed, cm-1): 3379, 2974, 1727, 1688, 1546, 1466, 1332, 1263, 1211, 1070, 1034, 1018, 843, 696.

References

[1] Patent: WO2011/80562, 2011, A1. Location in patent: Page/Page column 34
[2] Patent: WO2005/61487, 2005, A1. Location in patent: Page/Page column 109
[3] Patent: US2005/159469, 2005, A1. Location in patent: Page/Page column 56
[4] Patent: EP2423187, 2012, A1. Location in patent: Page/Page column 11
[5] Patent: US2005/131017, 2005, A1. Location in patent: Page/Page column 95

Methoxycarbonyl-L-tert-leucine(162537-11-3)Related Product Information

• Stearic acid
• tert-Butyl peroxyacetate
• N-CARBOBENZOXY-DL-LEUCINE
• tert-Butanol
• L-tert-Leucine
• Folic acid
• METHOXYCARBONYLSULFENYL CHLORIDE
• Ethyl 2-(Chlorosulfonyl)acetate
• Citric acid
• DL-Leucine
• Ascoric Acid
• Fmoc-L-tert-leucine
• (S)-N-Boc-3,3-dimethylpyrrolidine-2-carboxylic acid
• Cbz-L-tert-Leucine
• (2S,4R)-N-Boc-4-hydroxy-3,3-dimethylpyrrolidine-2-carboxylic acid
• Z-TLE-OH DCHA
• N-(METHOXYCARBONYL)-L-TERT-LEUCINE
• FMOC-D-ALPHA-T-BUTYLGLYCINE