Sodium hydride → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-bromo-6-chloropyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one

HRID 604607Notes

Reaction equation

HRID 604607 reaction equation
[F:1][C:2]([F:21])([F:20])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[NH:15][C@H:14]2[CH3:19])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[H-].[Na+].[Br:24][C:25]1[C:26]([CH2:32]Br)=[N:27][C:28]([Cl:31])=[CH:29][CH:30]=1>C1COCC1>[F:21][C:2]([F:1])([F:20])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:32][C:26]3[C:25]([Br:24])=[CH:30][CH:29]=[C:28]([Cl:31])[N:27]=3)[C@H:14]2[CH3:19])[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 232499153-Bromo-2-(bromomethyl)-6-chloropyridineHCID 23583229(4S,5R)-5-(3,5-bis(trifluoromethyl)phenyl)-4-methyloxazolidin-2-one

Product 1

HCID 57576268(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-bromo-6-chloropyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (4.55 g, 14.5 mmol) in THF (165 mL) was added sodium hydride (60% dispersion in mineral oil) (968 mg, 24.2 mmol) as a powder. The mixture was stirred at room temperature for 20 min. A solution of 3-bromo-2-(bromomethyl)-6-chloropyridine (2.5 g) in THF (30 mL) was added. The resulting mixture was stirred overnight at room temperature. The reaction was quenched with saturated NH4Cl and extracted with EtOAc (3×). The combined organic layers were washed with brine (1×), dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (Si, hexanes/EtOAc) to recover the unreacted 3-bromo-6-chloro-2-methylpyridine and to afford the title compound (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-bromo-6-chloropyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one. LCMS calc.=517.0; found=517.0 (M+1)+. 1H NMR (500 MHz, CDCl3) δ 7.92 (s, 1H); 7.84 (d, J=8.2 Hz, 1H); 7.83 (s, 2H); 7.21 (d, J=8.2 Hz, 1H); 5.89 (d, J=8.3 Hz, 1H); 5.04 (d, J=17.2 Hz, 1H); 4.47-4.41 (m, 1H); 4.35 (d, J=17.2 Hz, 1H); 0.83 (d, J=6.6 Hz, 3H).

Workup

  1. stirringThe resulting mixture was stirred overnight at room temperature
  2. customThe reaction was quenched with saturated NH4Cl
  3. extractionextracted with EtOAc (3×)
  4. washThe combined organic layers were washed with brine (1×)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (Si, hexanes/EtOAc)
  8. customto recover the unreacted 3-bromo-6-chloro-2-methylpyridine

Sources & evidence

ORD record
ord-2b2b5cef73f14f3fb5c5ea15620db728
Source dataset
uspto-grants-2011_03
Patent number
US07910592B2

Reaction notes

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