ChemicalBook CAS DataBase List (R,E)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)aMino)-2-Methylpent-2-enoate

(R,E)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)aMino)-2-Methylpent-2-enoate synthesis

13synthesis methods

Product Name:(R,E)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)aMino)-2-Methylpent-2-enoate
CAS Number:149709-59-1
Molecular formula:C25H31NO4
Molecular Weight:409.52

Propanoic acid, 3-(triphenylphosphoranylidene)-, ethyl ester

54356-04-6
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((R)-2-biphenyl-4-yl-1-forMylethyl)carbaMic acid t-butyl ester

149709-58-0
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(R,E)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)aMino)-2-Methylpent-2-enoate

149709-59-1
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$11.00/100mg

Yield:149709-59-1 79.08%

Reaction Conditions:

with Na₂S₂O₃ in dichloromethane;lithium hydroxide monohydrate at 0 - 10;Flow reactor;Large scale;

Steps:

1.4; 1.6-1.8; 2.4; 2.6-2.8; 3.4; 3.6-3.8 Example 1

(1) Preparation of material A solution: Compound II (100 Kg, 305.42 mol, 1.0 eq.) and TEMPO (9.54 Kg, 61.06 mol, 0.20 eq.) were dissolved in dichloromethane (680 Kg); (2) Preparation of material B solution: sodium bicarbonate (38.48 Kg, 458.12 mol, 1.5 eq.) and sodium bromide (1.88 Kg, 18.27 mol, 0.06 eq.) were dissolved in water (600 Kg); (3) Material C solution: sodium hypochlorite aqueous solution, the measured content is: 9.6%; (4) Preparation of material D solution: In the reactor, add water (200 Kg), dichloromethane (132.5 Kg), ethoxyformylethylenetriphenylphosphine (110 Kg, 305.42 mol, 1.0 eq. ) and sodium thiosulfate (15.16 Kg, 61.08 mol, 0.2 eq.), stirred and cooled to 05 for use; (5) Mix the material A solution and the material B solution in the micro-mixer 1 first, the residence time is 4-6 s, and then mix with the material C solution in the micro-mixer 2, the residence time is 3-5 s, and then Enter the microreactor for reaction, the residence time is 20-25 s, the temperature of the micro-mixer is 0-20 ; the temperature of the micro-reactor is 0-30 ; (6) The reaction solution obtained in step (5) is directly flowed into the reaction kettle containing the material D solution in step (4), and the reaction is stirred at a reaction temperature of 0 to 10 °C; (7) The reaction solution of step (6) is left to stand for stratification, the aqueous phase is extracted with dichloromethane, and the organic phases are combined and concentrated to obtain Sacubitril intermediate (IV); (8) Refining: the Sacubitril intermediate (IV) obtained in step (7) is heated and dissolved in ethanol, the system is in a light yellow and clear state, and water is added dropwise to the system while maintaining the temperature at 68-73°C, and there is solid Precipitation, turn off heating, gradient cooling, centrifugation, to obtain 138 Kg of wet product, and to obtain 98.92 Kg of refined intermediate (IV) after drying, yield: 79.08%, purity: 99.8998%.

References:

CN113754565,2021,A Location in patent:Paragraph 0030-0032; 0034

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5717-37-3 Synthesis