Sodium hydride → HCID 118468052, compound

HRID 2207111Notes

Reaction equation

HRID 2207111 reaction equation
[F:1][C:2]([F:21])([F:20])[C:3]1[CH:4]=[C:5]([C@H:13]2[S: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+].CS(O[CH2:29][C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=1[Br:40])(=O)=O>C1COCC1>[F:21][C:2]([F:1])([F:20])[C:3]1[CH:4]=[C:5]([C@H:13]2[S:17][C:16](=[O:18])[N:15]([CH2:29][C:30]3[CH:35]=[C:34]([C:36]([F:37])([F:39])[F:38])[CH:33]=[CH:32][C:31]=3[Br:40])[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 hydride2×HCID 88567977HCID 88567977, compoundHCID 90238165HCID 90238165, compound2×

Product 1

HCID 118468052HCID 118468052, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

To a solution of (4S,5R)-5-(3,5-bis(trifluoromethyl)phenyl)-4-methylthiazolidin-2-one (50 mg, 0.152 mmol) in THF (1 ml) was added NaH (7.59 mg, 0.190 mmol) at −20° C. 30 Minutes later, a solution of 2-bromo-5-(trifluoromethyl)benzyl methanesulfonate (50.6 mg, 0.152 mmol) in THF (0.5 ml) was added. Stirring of the reaction continued for 1 hour. A crude NMR spectrum showed only 25% product formation. The reaction temperature was increased to −10° C., and stirring was continued for another 1 h. The reaction mixture was left in the freezer under N2 atmosphere overnight. NMR and LCMS indicated around a 65% conversion to the desired isomer, with no undesired epimerized product. The reaction was cooled to −10° C., and additional NaH (2.429 mg, 0.061 mmol) was added. Stirring of the reaction mixture was continued for 20 minutes. 2-Bromo-5-(trifluoromethyl)benzyl methanesulfonate (20.2 mg, 0.061 mmol) was added, and the reaction was continued for another 2 hours at −10° C. The reaction mixture was quenched with ice water, and the mixture was diluted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by PTLC by using 35% EtOAc in hexane. 1H NMR (500 MHz, CDCl3): δ 7.90 (s, 1H); 7.85 (s, 2H); 7.76 (d, J=8.3 Hz, 1H); 7.59 (s, 1H); 7.48 (d, J=8.5 Hz, 1H); 5.15 (d, J=7.0 Hz, 1H); 5.02 (d, J=16.0 Hz, 1H); 4.45 (d, J=16.0 Hz, 1H); 4.10-4.11 (m, 1H); 0.97 (d, J=6.5 Hz, 3H).

Workup

  1. stirringstirring
  2. waitwas continued for another 1 h
  3. waitThe reaction mixture was left in the freezer under N2 atmosphere overnight
  4. temperatureThe reaction was cooled to −10° C.
  5. stirringStirring of the reaction mixture
  6. waitwas continued for 20 minutes
  7. waitthe reaction was continued for another 2 hours at −10° C
  8. customThe reaction mixture was quenched with ice water
  9. additionthe mixture was diluted with EtOAc
  10. washThe organic layer was washed with brine
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe residue was purified by PTLC

Sources & evidence

ORD record
ord-c77ea428003f44dfb6b6a8a3d8370cda
Source dataset
uspto-grants-2016_06
Patent number
US09376408B2

Reaction notes

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