Lithium Chloride → (S)-3-(4-(2-fluoro-5-(pyrimidin-2-yl)pyridin-3-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one

HRID 525333Notes

Reaction equation

HRID 525333 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([N:15]3[C@@H:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:18]([CH3:27])([CH3:26])[O:17][C:16]3=[O:28])=[CH:11][CH:10]=2)[C:5]([F:8])=[N:6][CH:7]=1.C([Sn](CCCC)(CCCC)[C:34]1[N:39]=[CH:38][CH:37]=[CH:36][N:35]=1)CCC.[Cl-].[Li+]>[Cu]I.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.CN(C=O)C>[F:8][C:5]1[C:4]([C:9]2[CH:14]=[CH:13][C:12]([N:15]3[C@@H:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:18]([CH3:27])([CH3:26])[O:17][C:16]3=[O:28])=[CH:11][CH:10]=2)=[CH:3][C:2]([C:34]2[N:39]=[CH:38][CH:37]=[CH:36][N:35]=2)=[CH:7][N:6]=1

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 27632512-(Tributylstannyl)pyrimidineHCID 89813722(S)-3-(4-(5-bromo-2-fluoropyridin-3-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one

Product 1

HCID 71736212(S)-3-(4-(2-fluoro-5-(pyrimidin-2-yl)pyridin-3-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-oneYield 42%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A resealable tube was charged with (S)-3-(4-(5-bromo-2-fluoropyridin-3-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one (0.050 g, 0.113 mmol), 2-(tributylstannyl)pyrimidine (commercially available from Frontier Scientific, Inc., Logan Utah) (0.056 mL, 0.170 mmol), lithium chloride (9.61 mg, 0.227 mmol), copper (I) iodide (2.158 mg, 0.011 mmol), and DMF (1.0 mL). Tetrakis(triphenylphosphine)palladium(0) (0.013 g, 0.011 mmol) was added, the system was purged with argon, and the tube was sealed. The mixture was then stirred at 100° C. for 12 hours. The reaction mixture was next concentrated to afford a brown oil. The residual oil was purified by column chromatography on silica gel (RediSep 40 g column, gradient elution with 0-50% EtOAc-hexane) to afford (S)-3-(4-(2-fluoro-5-(pyrimidin-2-yl)pyridin-3-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one (0.021 g, 0.048 mmol, 42% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.90-1.00 (m, 3H), 1.66 (s, 3H), 5.53 (s, 1H), 7.21-7.46 (m, 5H), 7.54 (t, J=4.89 Hz, 1H), 7.60-7.74 (m, 4H), 8.81 (dd, J=9.78, 2.35 Hz, 1H), 8.96 (d, J=4.89 Hz, 2H), 9.09 (dd, J=2.25, 1.08 Hz, 1H). m/z (ESI) 441 (M+H)+.

Workup

  1. customthe system was purged with argon
  2. customthe tube was sealed
  3. concentrationThe reaction mixture was next concentrated
  4. customto afford a brown oil
  5. customThe residual oil was purified by column chromatography on silica gel (RediSep 40 g column, gradient elution with 0-50% EtOAc-hexane)

Sources & evidence

ORD record
ord-8d8fdc2e0dab4c328dcd632b6d8c864e
Source dataset
uspto-grants-2016_05
Patent number
US09340549B2

Reaction notes

Loading…