Sodium hydride → (R,E)-Methyl 5-(3-(1,1-dioxido-3-(3-oxo-4-(3-(trifluoromethyl)phenyl)-but-1-en-1-yl)isothiazolidin-2-yl)propyl)thiophene-2-carboxylate

HRID 524365Notes

Reaction equation

HRID 524365 reaction equation
[H-].[Na+].[O:3]=[C:4]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=1)[CH2:5]P(=O)(OC)OC.[CH:23]([C@H:25]1[CH2:29][CH2:28][S:27](=[O:31])(=[O:30])[N:26]1[CH2:32][CH2:33][CH2:34][C:35]1[S:39][C:38]([C:40]([O:42][CH3:43])=[O:41])=[CH:37][CH:36]=1)=O>C1COCC1>[O:31]=[S:27]1(=[O:30])[CH2:28][CH2:29][C@H:25](/[CH:23]=[CH:5]/[C:4](=[O:3])[CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:20])([F:21])[F:22])[CH:14]=2)[N:26]1[CH2:32][CH2:33][CH2:34][C:35]1[S:39][C:38]([C:40]([O:42][CH3:43])=[O:41])=[CH:37][CH:36]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 17781240Dimethyl (2-oxo-3-(3-(trifluoromethyl)phenyl)propyl)-phosphonateHCID 118688787(R)-Methyl 5-(3-(3-formyl-1,1-dioxidoisothiazolidin-2-yl)propyl)thio-phene-2-carboxylate

Product 1

HCID 118688788(R,E)-Methyl 5-(3-(1,1-dioxido-3-(3-oxo-4-(3-(trifluoromethyl)phenyl)-but-1-en-1-yl)isothiazolidin-2-yl)propyl)thiophene-2-carboxylateYield 99%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a suspension of sodium hydride (12 mg, 0.5 mmol) in THF (1.0 mL) cooled to 0° C. was added a solution of dimethyl (2-oxo-3-(3-(trifluoromethyl)phenyl)propyl)-phosphonate (160 mg, 0.52 mmol) in THF (2.0 mL). After 15 min a solution of the aldehyde 11 (155 mg, 0.47 mmol) in THF (2.0 mL) was added. The reaction was allowed to warm room temperature and stirred for 16 h. The reaction was quenched with saturated aqueous ammonium chloride and extracted with EtOAc. The organic portion was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography (silica gel, 40% EtOAc/hex) afforded 240 mg (99%) of enone 12.

Workup

  1. temperatureto warm room temperature
  2. customThe reaction was quenched with saturated aqueous ammonium chloride
  3. extractionextracted with EtOAc
  4. washThe organic portion was washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue by flash column chromatography (silica gel, 40% EtOAc/hex)

Sources & evidence

ORD record
ord-e04d64c6998649be874c2577096693ef
Source dataset
uspto-grants-2016_05
Patent number
US09340534B2

Reaction notes

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