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

HRID 879688Notes

Reaction equation

HRID 879688 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)propanoate

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 in toluene (250 mL) was added 4-cyanobenzeneboronic acid, Pd(PPh3)4, 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 layer was washed with 10% Na2CO3 and 1 N HCl. The organic layer was dried over sodium sulfate and concentrated under reduced pressure to afford the crude product. The residue was then 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). LCMS (m/z) 382.

Workup

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

Sources & evidence

ORD record
ord-d30175c354d34db89bbbc0cbf3731429
Source dataset
uspto-grants-2015_03
Patent number
US08987295B2

Reaction notes

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