Potassium Carbonate → [2'-[(tert-Butoxycarbonyl-ethyl-amino)-methyl]-4'-(6-ethoxy-pyridin-3-yl)-6-methoxy-biphenyl-3-yl]-acetic acid ethyl ester

HRID 1625666Notes

Reaction equation

HRID 1625666 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH2:9][CH3:10])=[N:6][CH:7]=1.[CH2:11]([O:13][C:14](=[O:50])[CH2:15][C:16]1[CH:17]=[C:18]([C:24]2[CH:29]=[CH:28][C:27](B3OC(C)(C)C(C)(C)O3)=[CH:26][C:25]=2[CH2:39][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:41][CH3:42])[C:19]([O:22][CH3:23])=[CH:20][CH:21]=1)[CH3:12].C(=O)([O-])[O-].[K+].[K+]>COCCOC.C(OCC)(=O)C.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>[CH2:11]([O:13][C:14](=[O:50])[CH2:15][C:16]1[CH:17]=[C:18]([C:24]2[CH:29]=[CH:28][C:27]([C:2]3[CH:7]=[N:6][C:5]([O:8][CH2:9][CH3:10])=[CH:4][CH:3]=3)=[CH:26][C:25]=2[CH2:39][N:40]([C:43]([O:45][C:46]([CH3:47])([CH3:49])[CH3:48])=[O:44])[CH2:41][CH3:42])[C:19]([O:22][CH3:23])=[CH:20][CH:21]=1)[CH3:12]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 8172375-Bromo-2-ethoxypyridineHCID 58149092[2'-[(Tert-butoxycarbonyl-ethyl-amino)-methyl]-6-methoxy-4'-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-biphenyl-3-yl]-acetic acid ethyl ester

Product 1

HCID 58149276[2'-[(tert-Butoxycarbonyl-ethyl-amino)-methyl]-4'-(6-ethoxy-pyridin-3-yl)-6-methoxy-biphenyl-3-yl]-acetic acid ethyl ester

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

5-Bromo-2-ethoxypyridine (0.235 g, 1.16 mmol), [2′-[(tert-butoxycarbonyl-ethyl-amino)-methyl]-6-methoxy-4′-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-biphenyl-3-yl]-acetic acid ethyl ester (0.500 g, 0.903 mmol), and potassium carbonate (0.313 g, 2.3 mmol) were combined in DME (5 mL) and water (2.5 mL) under nitrogen. The mixture was purged with nitrogen, and then tetrakis(triphenylphosphine)palladium(0) (0.052 g, 0.045 mmol) was added, and the reaction was heated to 85° C. for 6 hours. Once no starting material was seen by analytical LCMS, the mixture was cooled to room temperature and diluted with ethyl acetate and water. The aqueous layer was separated and extracted with ethyl acetate, and the combined organic layers were dried over magnesium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography (0-40% ethyl acetate in hexanes) to give the title compound.

Workup

  1. customThe mixture was purged with nitrogen
  2. temperaturethe mixture was cooled to room temperature
  3. customThe aqueous layer was separated
  4. extractionextracted with ethyl acetate
  5. dry with materialthe combined organic layers were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography (0-40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-bd5598aa6393475782aa3f3723d77232
Source dataset
uspto-grants-2014_07
Patent number
US08785393B2

Reaction notes

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