Sodium Carbonate → (S)-3-(4-(5-bromo-2-fluoropyridin-3-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one

HRID 525332Notes

Reaction equation

HRID 525332 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C@@H:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:11]([CH3:20])([CH3:19])[O:10][C:9]2=[O:21])=[CH:4][CH:3]=1.[Br:22][C:23]1[CH:24]=[C:25](B(O)O)[C:26]([F:29])=[N:27][CH:28]=1.C(=O)([O-])[O-].[Na+].[Na+].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.O>[Br:22][C:23]1[CH:24]=[C:25]([C:2]2[CH:7]=[CH:6][C:5]([N:8]3[C@@H:12]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)[C:11]([CH3:20])([CH3:19])[O:10][C:9]3=[O:21])=[CH:4][CH:3]=2)[C:26]([F:29])=[N:27][CH:28]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 27832425-Bromo-2-fluoropyridine-3-boronic Acid (contains varying amounts of Anhydride)HCID 89813884(S)-3-(4-iodophenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one2×

Product 1

HCID 89813722(S)-3-(4-(5-bromo-2-fluoropyridin-3-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-oneYield 46.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A microwave vial was charged with (S)-3-(4-iodophenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one (Intermediate C)(0.200 g, 0.509 mmol), 5-bromo-2-fluoropyridine-3-boronic acid (0.224 g, 1.017 mmol)(commercially available from Alfa Aesar, Ward Hill, Mass.), sodium carbonate (0.162 g, 1.526 mmol), dioxane (3.0 mL), and water (0.600 mL). Tetrakis(triphenylphosphine)palladium(0) (0.059 g, 0.051 mmol) was added, the system was purged with argon, and the tube was sealed. The mixture was then stirred at 100° C. in the microwave for 1 hour. The resulting reaction mixture was filtered through Celite® brand filter aid and the filtrate was concentrated to afford a yellow oil. The residual oil was purified by column chromatography on silica gel (RediSep 40 g column, gradient elution with 0-25% EtOAc-hexane) to afford (S)-3-(4-(5-bromo-2-fluoropyridin-3-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one (0.104 g, 0.236 mmol, 46% yield) as a pale tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.92 (s, 3H), 1.64 (s, 3H), 5.52 (s, 1H), 7.07-7.47 (m, 5H), 7.51-7.75 (m, 4H), 8.15-8.44 (m, 2H). m/z (ESI) 441, 443 (M+H)+.

Workup

  1. customthe system was purged with argon
  2. customthe tube was sealed
  3. customThe resulting reaction mixture
  4. filtrationwas filtered through Celite® brand
  5. filtrationfilter aid
  6. concentrationthe filtrate was concentrated
  7. customto afford a yellow oil
  8. customThe residual oil was purified by column chromatography on silica gel (RediSep 40 g column, gradient elution with 0-25% EtOAc-hexane)

Sources & evidence

ORD record
ord-b5567f844fca4c869972368993c8f4e4
Source dataset
uspto-grants-2016_05
Patent number
US09340549B2

Reaction notes

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