Sodium hydride → HCID 118468050, compound

HRID 2207112Notes

Reaction equation

HRID 2207112 reaction equation
[H-].[Na+].[F:3][C:4]([F:23])([F:22])[C:5]1[CH:6]=[C:7]([C@H:15]2[S:19][C:18](=[O:20])[NH:17][C@H:16]2[CH3:21])[CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1.CS(O[CH2:29][C:30]1[C:35]([Cl:36])=[CH:34][CH:33]=[C:32]([C:37]([F:40])([F:39])[F:38])[N:31]=1)(=O)=O>C1COCC1>[F:23][C:4]([F:3])([F:22])[C:5]1[CH:6]=[C:7]([C@H:15]2[S:19][C:18](=[O:20])[N:17]([CH2:29][C:30]3[C:35]([Cl:36])=[CH:34][CH:33]=[C:32]([C:37]([F:39])([F:38])[F:40])[N:31]=3)[C@H:16]2[CH3:21])[CH:8]=[C:9]([C:11]([F:12])([F:13])[F:14])[CH:10]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 88567977HCID 88567977, compoundHCID 90237821HCID 90237821, compound

Product 1

HCID 118468050HCID 118468050, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-10 °C

Procedure

A solution of NaH (18 mg, 0.46 mmol) in THF (2.0 ml) was cooled to −20° C. To this was added a solution of (4S,5R)-5-(3,5-bis(trifluoromethyl)phenyl)-4-methylthiazolidin-2-one (100 mg, 0.304 mmol) in THF (1.0 ml) dropwise at the same temperature. The reaction was allowed to warm to −10° C. over 1 hour. A solution of (3-chloro-6-(trifluoromethyl)pyridin-2-yl)methyl methanesulfonate (106 mg, 0.364 mmol) in THF (1.0 ml) was added via syringe. Stirring of the reaction was continued at −10° C. for 5 hours. The reaction was quenched by addition of ice water and diluted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated. The compound was purified by column chromatography to yield (4S,5R)-5-(3,5-bis(trifluoromethyl)phenyl)-3-((3-chloro-6-(trifluoromethyl)pyridin-2-yl)methyl)-4-methylthiazolidin-2-one. 1H NMR (500 MHz, CDCl3): δ 7.91 (d, J=8.2 Hz, 1H); 7.89 (s, 1H); 7.85 (s, 2H); 7.64 (d, J=8.3 Hz, 1H); 5.36 (d, J=17.5 Hz, 1H); 5.24 (d, J=6.9 Hz, 1H); 4.54-4.55 (m, 1H); 4.37 (d, J=17.5 Hz, 1H); 0.99 (d, J=6.6 Hz, 4H).

Workup

  1. customThe reaction was quenched by addition of ice water
  2. additiondiluted with EtOAc
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe compound was purified by column chromatography

Sources & evidence

ORD record
ord-e7912c65b7bb466aa6408a0388918726
Source dataset
uspto-grants-2016_06
Patent number
US09376408B2

Reaction notes

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