Nitrogen → (S)-Methyl 3-([1,1'-biphenyl]-4-yl)-2-((tert-butoxycarbonyl)amino)propanoate

HRID 449484Notes

Reaction equation

HRID 449484 reaction equation
C(=O)([O-])[O-].[K+].[K+].[CH3:7][O:8][C:9](=[O:34])[C@@H:10]([NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:11][C:12]1[CH:17]=[CH:16][C:15](OS(C(F)(F)F)(=O)=O)=[CH:14][CH:13]=1.[C:35]1(B(O)O)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.N#N>O.O1CCOCC1.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>[C:15]1([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:16]=[CH:17][C:12]([CH2:11][C@H:10]([NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:9]([O:8][CH3:7])=[O:34])=[CH:13][CH:14]=1

Participants

8

Reactant 4

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 10455198(S)-Methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(((trifluoromethyl)sulfonyl)oxy)phenyl)propanoate

Product 1

HCID 10286882(S)-Methyl 3-([1,1'-biphenyl]-4-yl)-2-((tert-butoxycarbonyl)amino)propanoateYield 84.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Potassium carbonate (50 mg, 0.4 mmol) in water (0.2 mL) was added to a solution of (S)-2-tert-butoxycarbonylamino-3-(4-trifluoromethanesulfonyloxy-phenyl)-propionic acid methyl ester (50 mg, 0.1 mmol), and phenylboronic acid (Aldrich, Cat P20009) (21 mg, 0.18 mmol) in 1,4-dioxane (3.0 mL). The reaction was degassed by N2 for 5 min Tetrakis(triphenylphosphine)palladium(0) (8 mg, 0.007 mmol) was added, and the reaction was degassed for another 5 min The reaction vial was sealed and stirred for 5 h. at 80° C. The reaction was partitioned between water and ethyl acetate. The organic phase was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by Flash chromatography on a silica gel column (EtOAC:Hexanes, 1:3 to 1:1) to give the (S)-methyl 3-(biphenyl-4-yl)-2-(tert-butoxycarbonylamino)propanoate (30 mg, 70%). Analytical LCMS (M+H-Boc)+: m/z=256.1.

Workup

  1. additionwas added
  2. customthe reaction was degassed for another 5 min
  3. customThe reaction
  4. customvial was sealed
  5. customThe reaction was partitioned between water and ethyl acetate
  6. washThe organic phase was washed with saturated brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was purified by Flash chromatography on a silica gel column (EtOAC:Hexanes, 1:3 to 1:1)

Sources & evidence

ORD record
ord-0e123d6c206548e7a4bdf02e222b3117
Source dataset
uspto-grants-2013_07
Patent number
US08481732B2

Reaction notes

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