Sodium hydride → methyl 2''-{(4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-4-methyl-2-oxo-1,3-oxazolidin-5-yl}-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

HRID 2093189Notes

Reaction equation

HRID 2093189 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([O:17][CH3:18])=[O:16])=[CH:11][C:10]=2[CH3:19])=[CH:5][C:4]=1[C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][C:21]=1[C@H:30]1[O:34][C:33](=[O:35])[NH:32][C@@H:31]1[CH3:36].[H-].[Na+].Br[CH2:40][C:41]1[CH:46]=[C:45]([C:47]([F:50])([F:49])[F:48])[CH:44]=[C:43]([C:51]([F:54])([F:53])[F:52])[CH:42]=1>C1COCC1>[F:48][C:47]([F:49])([F:50])[C:45]1[CH:46]=[C:41]([CH:42]=[C:43]([C:51]([F:54])([F:52])[F:53])[CH:44]=1)[CH2:40][N:32]1[C@H:31]([CH3:36])[C@@H:30]([C:21]2[CH:22]=[C:23]([C:26]([F:27])([F:28])[F:29])[CH:24]=[CH:25][C:20]=2[C:4]2[CH:5]=[C:6]([C:9]3[CH:14]=[CH:13][C:12]([C:15]([O:17][CH3:18])=[O:16])=[CH:11][C:10]=3[CH3:19])[CH:7]=[CH:8][C:3]=2[O:2][CH3:1])[O:34][C:33]1=[O:35]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 67065997methyl 4'-methoxy-2-methyl-2''-[(4R,5R)-4-methyl-2-oxo-1,3-oxazolidin-5-yl]-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

Product 1

HCID 86630542methyl 2''-{(4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-4-methyl-2-oxo-1,3-oxazolidin-5-yl}-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The starting methyl 4′-methoxy-2-methyl-2″-[(4R,5R)-4-methyl-2-oxo-1,3-oxazolidin-5-yl]-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (40 mg, 0.080 mmol) was dissolved in anhydrous THF (1 mL) and cooled in an ice bath. Sodium hydride (60% w/w in mineral oil, 3.5 mg, 0.088 mmol) was added into the mixture. The reaction mixture was stirred cold (ice bath) for 10 min followed by addition of 1-(bromomethyl)-3,5-bis(trifluoromethyl)benzene (22 μL, 36.8 mg, 0.120 mmol). The resulting mixture was stirred cold for 20 min then the cold bath was removed. Aliquot at reaction time 2.5 hours indicated about 50% conversion. Reaction crude was cooled (ice bath) and quenched by NH4Cl (aq., sat.). The resulting bi-phasic mixture was worked up with ethyl acetate. The combined organic extracts were dried over Na2SO4, filtered, and concentrated to afford an oil. This oil was purified by a preparative reverse-phase HPLC (Kromasil 100-5C18, 100×21.1 mm) eluted with a MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v) gradient mixture. Related fractions were pooled and evaporated to afford methyl 2″-{(4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-4-methyl-2-oxo-1,3-oxazolidin-5-yl}-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate. Un-reacted starting material was also recovered. LCMS calc.=725.18; found=726.19 (M+1).

Workup

  1. temperaturecooled in an ice bath
  2. stirringThe resulting mixture was stirred cold for 20 min
  3. customthe cold bath was removed
  4. customAliquot at reaction time 2.5 hours
  5. customReaction crude
  6. temperaturewas cooled (ice bath)
  7. customquenched by NH4Cl (aq., sat.)
  8. dry with materialThe combined organic extracts were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto afford an oil
  12. customThis oil was purified by a preparative reverse-phase HPLC (Kromasil 100-5C18, 100×21.1 mm)
  13. washeluted with a MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v) gradient mixture
  14. customevaporated

Sources & evidence

ORD record
ord-7442b154a06348a498acff90a228c030
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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