(S)-4-Benzyl-2-oxazolidinone → HCID 25009870, compound

HRID 2093226Notes

Reaction equation

HRID 2093226 reaction equation
[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[NH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC([O-])(C)C.[K+].Br[CH2:21][C:22]1[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:23]=1[C:32]1[CH:33]=[C:34]([C:40]2[CH:45]=[CH:44][C:43]([C:46]([O:48]C)=[O:47])=[CH:42][C:41]=2[CH3:50])[CH:35]=[CH:36][C:37]=1[O:38][CH3:39]>CN(C=O)C>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[CH2:21][C:22]1[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:23]=1[C:32]1[CH:33]=[C:34]([C:40]2[CH:45]=[CH:44][C:43]([C:46]([OH:48])=[O:47])=[CH:42][C:41]=2[CH3:50])[CH:35]=[CH:36][C:37]=1[O:38][CH3:39])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 736225(S)-4-Benzyl-2-oxazolidinoneHCID 23665647Potassium tert-butoxideHCID 57544358Methyl 2''-(bromomethyl)-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

Product 1

HCID 25009870HCID 25009870, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of (4S)-4-benzyl-1,3-oxazolidin-2-one (29.8 mg, 0.168 mmol) in DMF (1.5 mL) was added t-BuOK (17.5 mg, 0.152 mmol). After 10 minutes, a solution of methyl 2″-(bromomethyl)-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (75 mg, 0.152 mmol) in DMF (1.5 mL) was added by cannula. The reaction was stirred for 30 minutes, and then quenched with saturated NH4Cl solution (10 mL), diluted with EtOAc (15 mL), washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated. The residue was dissolved with MeOH (2 mL) and 4M KOH solution (0.5 mL) was added. The reaction was stirred at room temperature for 2 hours, then stored in the freezer for 16 hours. The reaction was warmed to room temperature, and stirred for 2 hours. The reaction was quenched with 1 N HCl solution (5 mL), diluted with EtOAc (15 mL), washed with brine (5 mL), dried over Na2SO4, filtered, and concentrated. The residue was purified by reverse-phase chromatography (C-18, 10 to 95% MeCN/water with 0.1% TFA), followed by lyophilization to afford 2″-{[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]methyl}-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylic acid LCMS=576.0 (M+1)+. 1H NMR (CDCl3, 500 MHz, rotamers present) δ 8.01-7.86 (m, 2H), 7.67-7.50 (m, 2H), 7.44-7.32 (m, 3H), 7.23-7.07 (m, 5H), 6.91-6.85 (m, 2H), 4.92-4.58 (m, 2H), 4.27 (d, J=15.6 Hz), 4.11 (d, J=15.6 Hz), 4.06-3.82 (m, 5H), 3.64-3.51 (m, 1H), 2.86-2.71 (m, 1H), 2.47-2.28 (m, 4H).

Workup

  1. customquenched with saturated NH4Cl solution (10 mL)
  2. additiondiluted with EtOAc (15 mL)
  3. washwashed with brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved with MeOH (2 mL) and 4M KOH solution (0.5 mL)
  8. additionwas added
  9. stirringThe reaction was stirred at room temperature for 2 hours
  10. waitstored in the freezer for 16 hours
  11. stirringstirred for 2 hours
  12. customThe reaction was quenched with 1 N HCl solution (5 mL)
  13. additiondiluted with EtOAc (15 mL)
  14. washwashed with brine (5 mL)
  15. dry with materialdried over Na2SO4
  16. filtrationfiltered
  17. concentrationconcentrated
  18. customThe residue was purified by reverse-phase chromatography (C-18, 10 to 95% MeCN/water with 0.1% TFA)

Sources & evidence

ORD record
ord-438c42e51b8646e5a86d212e1ce9505c
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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