(R,E)-5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)aMino)-2-Methylpent-2-enoic acid Chemical Properties

Melting point:

188 - 191°C

Boiling point:

595.6±50.0 °C(Predicted)

Density 

1.132±0.06 g/cm3(Predicted)

vapor pressure 

8.4-839.931Pa at 20℃

storage temp. 

Sealed in dry,Room Temperature

solubility 

DMSO (Slightly), Methanol (Slightly)

pka

4.67±0.19(Predicted)

form 

Solid

color 

White to Off-White

InChI

InChI=1S/C23H27NO4/c1-16(21(25)26)14-20(24-22(27)28-23(2,3)4)15-17-10-12-19(13-11-17)18-8-6-5-7-9-18/h5-14,20H,15H2,1-4H3,(H,24,27)(H,25,26)/b16-14+/t20-/m0/s1

InChIKey

JXTNUXJSXXIIFE-VISDOYDDSA-N

SMILES

C(O)(=O)/C(/C)=C/[C@H](NC(OC(C)(C)C)=O)CC1=CC=C(C2=CC=CC=C2)C=C1

LogP

2.2-3.6 at 25℃ and pH2.5-7

(R,E)-5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)aMino)-2-Methylpent-2-enoic acid Usage And Synthesis

Uses

(R,E)-5-([1,1-Biphenyl]-4-yl)-4-((tert-butoxycarbonyl)aMino)-2-methylpent-2-enoic Acid is used in preparation of sacubitril intermediate using Nickel Salt catalyst.

Synthesis

The general procedure for the synthesis of (R,E)-5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)amino)-2-methyl-2-pentenoic acid from ethyl (4R)-5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)amino)-2-methyl-2-pentenoic acid was as follows: Step 1: 800 g of 95% ethanol and 400 g of pure water were mixed, compound I (1.3 mol) and lithium hydroxide (0.1833 mol) were added, and the reaction was held at reflux for 1 hour at 80 °C. After completion of the reaction, it was cooled to room temperature, activated carbon was added, heated to 42 °C and then continued to raise the temperature to 80 °C reflux. Incubate at room temperature for 2 hours. Step 2: The reaction mixture was thermally filtered and aqueous citric acid was added to the filtrate to terminate the reaction. Subsequently, the mixture was heated at reflux at 80°C for 1 hour and cooled to room temperature to crystallize. The crystals were collected by filtration and dried to give 55.4 g of dry Compound II in 79.05% molar yield and 99.20% purity.

References

[1] Patent: EP1903027, 2008, A1. Location in patent: Page/Page column 17
[2] Patent: CN106431993, 2017, A. Location in patent: Paragraph 0039; 0045; 0051; 0057
[3] Patent: CN106631903, 2017, A. Location in patent: Paragraph 0031; 0032; 0033
[4] Patent: CN106946742, 2017, A. Location in patent: Paragraph 0011

(R,E)-5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)aMino)-2-Methylpent-2-enoic acid(1012341-48-8)Related Product Information

• (2R,4S)-4-([1,1'-Biphenyl]-4-ylmethyl)-4-(4-ethoxy-4-oxobutanamido)-2-methylbutanoic acid
• AHU-377 (heMicalciuM salt)
• (2R,4S)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-aMino-2-Methylpentanoate
• (2R,4R)-5-(Biphenyl-4-yl)-4-[(tert-butoxycarbonyl)amino]-2-methylpentanoic acid
• (2S,4R)-5-(Biphenyl-4-yl)-4-[(tert-butoxycarbonyl)amino]-2-methylpentanoic acid
• (S)-5-[(Biphenyl-4-yl)methyl]-1-(2,2-dimethylpropionyl)pyrrolidin-2-one
• ((R)-2-biphenyl-4-yl-1-forMylethyl)carbaMic acid t-butyl ester
• 2-Pyrrolidinone, 5-([1,1'-biphenyl]-4-ylMethyl)-3-Methyl-, (3R,5S)-
• Valsartan
• (2R,4S)-5-([1,1'-biphenyl]-4-yl)-4-aMino-2-Methylpentanoic acid hydrochloride
• LCZ696
• LCZ Impurity
• (S)-5-[(Biphenyl-4-yl)carbonyl]pyrrolidin-2-one
• AHU-377
• (2R,4S)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)aMino)-2-Methylpentanoate
• (2S,4S)-5-(Biphenyl-4-yl)-4-[(tert-butoxycarbonyl)amino]-2-methylpentanoic acid
• LCZ696 InteMediate
• Sacubitril Impurity 72