Sodium hydride → HCID 58914778, compound

HRID 2242012Notes

Reaction equation

HRID 2242012 reaction equation
[H-].[Na+].CC1C=CC(S([CH2:13][N+:14]#[C-:15])(=O)=O)=CC=1.[Cl:16][C:17]1[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:18]=1/[CH:24]=[CH:25]/[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27].CCOC(C)=O.CCCCCC>CCOCC.CS(C)=O>[Cl:16][C:17]1[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:18]=1[C:24]1[C:25]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[CH:13][NH:14][CH:15]=1

Participants

7

Reactant 4

HCID 24758Sodium hydride2×HCID 161915Tosylmethyl isocyanideHCID 21226206Ethyl acetate hexaneHCID 58914774HCID 58914774, compound

Product 1

HCID 58914778HCID 58914778, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 3283Diethyl EtherSolvent2×

Procedure

Dry ether was added to NaH (1.5 eq as the oil dispersion) under argon. After decanting off the ether via syringe, the NaH was suspended again with fresh ether under argon. A solution of TOSMIC (1.1 eq) and 2 (1 eq) dissolved in a mixture of ether and DMSO was added dropwise to the stirred suspension of NaH at 0° C. over 20-30 min. The addition was mildly exothermic and evolved gas. After the addition, the reaction was allowed to warm to ambient rt. The progress of the reaction was followed by TLC (25% EtOAc/Hexane, the UV active product was at Rf=0.4) and LCMS until done (−2-3 h). Upon completion, the reaction was carefully quenched with sat. aq. NH4Cl (added slowly to avoid strong gas evolution and exotherm) and diluted with ether. The layers were separated and the organic phase washed with sat. aq. NaHCO3, water, and brine. The crude dark solid can be purified by recrystallization. Best results were achieved either through recrystallization directly from a mixture of hot EtOAc/hexane (1:3 v/v) or by dissolving the crude product in minimal hot EtOAc followed by addition of hexane (−2 volumes of hexane based on the volume of EtOAc). The hot solutions were allowed to cool to room temperature and age over night. The crystals were first filtered and then washed with hexane giving 99% pure product in 60-70% yield.

Workup

  1. customAfter decanting off the ether via syringe
  2. additionThe addition
  3. additionAfter the addition
  4. custom(−2-3 h)
  5. customUpon completion, the reaction was carefully quenched with sat. aq. NH4Cl (
  6. additionadded slowly
  7. additiondiluted with ether
  8. customThe layers were separated
  9. washthe organic phase washed with sat. aq. NaHCO3, water, and brine
  10. customThe crude dark solid can be purified by recrystallization
  11. customBest results
  12. customwere achieved either through recrystallization directly from a mixture of hot EtOAc/hexane (1:3 v/v)
  13. dissolutionby dissolving the crude product in minimal hot EtOAc
  14. additionfollowed by addition of hexane (−2 volumes of hexane
  15. temperatureto cool to room temperature
  16. waitage over night
  17. filtrationThe crystals were first filtered
  18. washwashed with hexane giving 99% pure product in 60-70% yield

Sources & evidence

ORD record
ord-e36a5ecaa5e7472a905236a8cd151df2
Source dataset
uspto-grants-2010_03
Patent number
US07671049B2

Reaction notes

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