Sodium Carbonate → (S)-3-(4-(6-fluoro-[3,3'-bipyridin]-5-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one

HRID 525400Notes

Reaction equation

HRID 525400 reaction equation
[F:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[C@@H:18]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[C:17]([CH3:26])([CH3:25])[O:16][C:15]3=[O:27])=[CH:10][CH:9]=2)=[CH:6][C:5](C2N=CC=CN=2)=[CH:4][N:3]=1.[N:34]1[CH:39]=[CH:38][CH:37]=[C:36](B(O)O)[CH:35]=1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[F:1][C:2]1[N:3]=[CH:4][C:5]([C:36]2[CH:35]=[N:34][CH:39]=[CH:38][CH:37]=2)=[CH:6][C:7]=1[C:8]1[CH:9]=[CH:10][C:11]([N:14]2[C@@H:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:17]([CH3:25])([CH3:26])[O:16][C:15]2=[O:27])=[CH:12][CH:13]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 27343783-Pyridinylboronic acidHCID 71736212(S)-3-(4-(2-fluoro-5-(pyrimidin-2-yl)pyridin-3-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one

Product 1

HCID 89814120(S)-3-(4-(6-fluoro-[3,3'-bipyridin]-5-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-oneYield 83%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A microwave vial was charged with (S)-3-(4-(5-bromo-2-fluoropyridin-3-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one (Example 3)(0.040 g, 0.091 mmol), 3-pyridylboronic acid (commercially available from Sigma-Aldrich, Milwaukee, Wis., 0.022 g, 0.181 mmol), sodium carbonate (0.029 g, 0.272 mmol), dioxane (2.0 mL), and water (0.40 mL). Tetrakis(triphenylphosphine)-palladium(0) (10.47 mg, 9.06 mol) 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 reaction mixture was next filtered through Celite® brand filter aid and the filtrate was concentrated to afford a yellow oil. The oil thus obtained was purified using column chromatography on silica gel (RediSep 40 g column, gradient elution with 50-100% EtOAc-hexane) to afford (S)-3-(4-(6-fluoro-[3,3′-bipyridin]-5-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one (0.033 g, 0.075 mmol, 83% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.93 (s, 3H), 1.65 (s, 3H), 5.53 (s, 1H), 7.24-7.45 (m, 5H), 7.51 (ddd, J=8.00, 4.82, 0.88 Hz, 1H), 7.60-7.75 (m, 4H), 8.23 (ddd, J=8.00, 2.42, 1.61 Hz, 1H), 8.41 (dd, J=9.63, 2.49 Hz, 1H), 8.56 (dd, J=2.40, 1.32 Hz, 1H), 8.62 (dd, J=4.74, 1.61 Hz, 1H), 9.02 (dd, J=2.45, 0.78 Hz, 1H). m/z (ESI) 440 (M+H)+.

Workup

  1. customthe system was purged with argon
  2. customthe tube was sealed
  3. filtrationThe reaction mixture was next filtered through Celite® brand
  4. filtrationfilter aid
  5. concentrationthe filtrate was concentrated
  6. customto afford a yellow oil
  7. customThe oil thus obtained
  8. customwas purified

Sources & evidence

ORD record
ord-a238638dd15a4481a6e70041d06a9ec8
Source dataset
uspto-grants-2016_05
Patent number
US09340549B2

Reaction notes

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