Sodium Carbonate → Methyl (s)-2-((tert-butoxycarbonyl)amino)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl)propanoate

HRID 391788Notes

Reaction equation

HRID 391788 reaction equation
[CH3:1][O:2][C:3](=[O:29])[C@@H:4]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:5][C:6]1[CH:11]=[CH:10][C:9](B2OC(C)(C)C(C)(C)O2)=[CH:8][CH:7]=1.Br[C:31]1[CH:36]=[CH:35][N:34]=[C:33]([CH3:37])[C:32]=1[CH3:38].C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.O.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:29])[C@@H:4]([NH:21][C:22]([O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:23])[CH2:5][C:6]1[CH:7]=[CH:8][C:9]([C:31]2[CH:36]=[CH:35][N:34]=[C:33]([CH3:37])[C:32]=2[CH3:38])=[CH:10][CH:11]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 10949509methyl (2S)-2-{[(tert-butoxy)carbonyl]amino}-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propanoateHCID 223179414-Bromo-2,3-dimethylpyridine

Product 1

HCID 66719739Methyl (s)-2-((tert-butoxycarbonyl)amino)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl)propanoateYield 57.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

Suzuki coupling.: To a mixture of (S)-2-tert-butoxycarbonylamino-3-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propionic acid methyl ester (8.22 g) in 140 mL toluene and 40 mL water was added 4-bromo-2,3-dimethyl-pyridine (6.77 g), Na2CO3 (7.5 g), and Pd(PPh3)4. The mixture was purged with nitrogen and stirred under nitrogen at 80° C. for 18 h. The mixture was then cooled to rt and poured into water-EtOAc. The organic layer was washed with water and saturated brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (hexanes-EtOAc) to provide (S)-2-tert-butoxycarbonylamino-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid methyl ester (4.5 g). LCMS (m/z) 386.

Workup

  1. customThe mixture was purged with nitrogen
  2. temperatureThe mixture was then cooled to rt
  3. additionpoured into water-EtOAc
  4. washThe organic layer was washed with water and saturated brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography (hexanes-EtOAc)

Sources & evidence

ORD record
ord-b604ee88c08347c1accbb2ad1cd9a0ab
Source dataset
uspto-grants-2013_02
Patent number
US08383644B2

Reaction notes

Loading…