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 1508504Notes

Reaction equation

HRID 1508504 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 (4.94 g, 15.77 mmol) in THF (75 mL) was added NaH (60% dispersion in mineral oil) (0.526 g, 13.14 mmol). After stirring the reaction at room temperature for 10 minutes, 3-bromo-2-(bromomethyl)-6-chloropyridine (3.0 g, 10.51 mmol) was added as a solution in THF (20 mL). The reaction was stirred at room temperature for 16 hours and then quenched with saturated NH4Cl (40 mL). The mixture was diluted with EtOAc (100 mL) and hexanes (50 mL). The organic layer was washed with water (2×100 mL) and brine (50 mL), dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel with 0 to 50% EtOAc/hexanes afforded (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-bromo-6-chloropyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one. LCMS=518.8 (M+H)+ 1H NMR (CDCl3, 500 MHz) δ 7.90 (s, 1H), 7.81-7.83 (m, 3H), 7.18 (d, J=8.5 Hz, 1H), 5.87 (d, J=8.5 Hz, 1H), 5.02 (d, J=17.2 Hz, 1H), 4.42 (m, 1H), 4.32 (d, J=17.1 Hz, 1H), 0.80 (d, J=6.6 Hz, 3H).

Workup

  1. customthe reaction at room temperature for 10 minutes
  2. stirringThe reaction was stirred at room temperature for 16 hours
  3. customquenched with saturated NH4Cl (40 mL)
  4. additionThe mixture was diluted with EtOAc (100 mL) and hexanes (50 mL)
  5. washThe organic layer was washed with water (2×100 mL) and brine (50 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification of the residue by flash chromatography on silica gel with 0 to 50% EtOAc/hexanes

Sources & evidence

ORD record
ord-6dc97fecb15d4225bc6dd1fef74a6cca
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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