Potassium Carbonate → methyl 4'-{(1R)-1-[(tert-butoxycarbonyl)amino]ethyl)-3-fluoro-1,1'-biphenyl-2-carboxylate

HRID 896709Notes

Reaction equation

HRID 896709 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([C@H:15]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH3:16])=[CH:11][CH:10]=2)O1.[F:26][C:27]1[CH:36]=[CH:35][CH:34]=[C:33](I)[C:28]=1[C:29]([O:31][CH3:32])=[O:30].C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C1COCC1.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[C:20]([O:19][C:18]([NH:17][C@@H:15]([C:12]1[CH:11]=[CH:10][C:9]([C:33]2[C:28]([C:29]([O:31][CH3:32])=[O:30])=[C:27]([F:26])[CH:36]=[CH:35][CH:34]=2)=[CH:14][CH:13]=1)[CH3:16])=[O:24])([CH3:21])([CH3:22])[CH3:23]

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 80271Tri-o-tolylphosphineHCID 12192164Methyl 2-fluoro-6-iodobenzoateHCID 67467206tert-Butyl (R)-(1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)carbamate

Product 1

HCID 68519014methyl 4'-{(1R)-1-[(tert-butoxycarbonyl)amino]ethyl)-3-fluoro-1,1'-biphenyl-2-carboxylateYield 18.9%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of tert-butyl (1R)-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethylcarbamate (1.0 g, 2.9 mmol) and methyl 2-fluoro-6-iodobenzoate (1.2 g, 4.32 mmol) in 25 mL of a 5:1 THF:water mixture was added potassium carbonate (1.2 g, 8.64 mmol), tri-o-tolylphosphine (350 mg, 1.15 mmol) and lastly palladium acetate (65 mg, 0.29 mmol). The reaction vessel was then sealed and placed into a 90° C. oil bath for overnight stirring and heating. After about 18 hours the reaction mixture was cooled to ambient temperature and then diluted with EtOAc. The organics were washed with brine (×4), dried over sodium sulfate, filtered, and concentrated under reduced pressure to give an oil. This oil was subject to silica gel chromatography eluting with 10-60% EtOAc in hexanes to provide methyl 4′-{(1R)-1-[(tert-butoxycarbonyl)amino]ethyl}-3-fluoro-1,1′-biphenyl-2-carboxylate (205 mg), found to be pure by LC/MS and proton NMR.

Workup

  1. customThe reaction vessel was then sealed
  2. customplaced into a 90° C.
  3. customfor overnight
  4. temperatureheating
  5. washThe organics were washed with brine (×4)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give an oil
  10. washeluting with 10-60% EtOAc in hexanes

Sources & evidence

ORD record
ord-b476d44bc70745e6bff8bd43b0f2adea
Source dataset
uspto-grants-2005_07
Patent number
US06919343B2

Reaction notes

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