Sodium Carbonate → Methyl (s)-2-((tert-butoxycarbonyl)amino)-3-(4'-cyano-[1,1'-biphenyl]-4-yl)propanoate

HRID 39060Notes

Reaction equation

HRID 39060 reaction equation
[CH3:1][O:2][C:3](=[O:21])[C@@H:4]([NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:5][C:6]1[CH:11]=[CH:10][C:9](Br)=[CH:8][CH:7]=1.[C:22]([C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1)#[N:23].C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3](=[O:21])[C@@H:4]([NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:27]2[CH:28]=[CH:29][C:24]([C:22]#[N:23])=[CH:25][CH:26]=2)=[CH:8][CH:7]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343264-Cyanophenylboronic acidHCID 12967061(S)-Methyl 3-(4-bromophenyl)-2-((tert-butoxycarbonyl)amino)propanoate

Product 1

HCID 66719271Methyl (s)-2-((tert-butoxycarbonyl)amino)-3-(4'-cyano-[1,1'-biphenyl]-4-yl)propanoateYield 68.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

Suzuki coupling: To a solution of (S)-3-(4-Bromo-phenyl)-2-tert-butoxycarbonylamino-propionic acid methyl ester (70.1 mmol) in toluene (250 mL) was added 4-cyanobenzeneboronic acid (105 mmol), Pd(PPh3)4 (3.5 mmol), and 1N Na2CO3 solution (105 mL). The mixture was heated at reflux for 7 h. After completion of the reaction, the aqueous layer was drained. The organic was washed with 10% Na2CO3 and 1 N HCl. The organic was dried over sodium sulfate and concentrated under reduced pressure to afford the crude product. The residue was purified by column chromatography (hexanes-EtOAc) to provide (S)-2-tert-Butoxycarbonylamino-3-(4′-cyano-biphenyl-4-yl)-propionic acid methyl ester (18.2 g). LC-MS (m/z) 382.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 7 h
  3. customAfter completion of the reaction
  4. washThe organic was washed with 10% Na2CO3 and 1 N HCl
  5. dry with materialThe organic was dried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customto afford the crude product
  8. customThe residue was purified by column chromatography (hexanes-EtOAc)

Sources & evidence

ORD record
ord-cdee7bbac04b46c2b7ccfc5ab6dbad03
Source dataset
uspto-grants-2013_09
Patent number
US08524708B2

Reaction notes

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