Sodium Sulfite → Methyl 4-({cyclohexyl[2-ethyl-5-(2-methylpropanoyl)thiophen-3-yl]methyl}amino)benzoate

HRID 1877259Notes

Reaction equation

HRID 1877259 reaction equation
[CH:1]1([CH:7]([NH:17][C:18]2[CH:27]=[CH:26][C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:20][CH:19]=2)[C:8]2[CH:12]=[C:11]([CH:13]=[O:14])[S:10][C:9]=2[CH2:15][CH3:16])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:28]([Mg]Br)([CH3:30])[CH3:29].O1CCCC1.[Cl-].[NH4+].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.S([O-])([O-])=O.[Na+].[Na+]>O1CCCC1.C(Cl)Cl>[CH:1]1([CH:7]([NH:17][C:18]2[CH:27]=[CH:26][C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:20][CH:19]=2)[C:8]2[CH:12]=[C:11]([C:13](=[O:14])[CH:28]([CH3:30])[CH3:29])[S:10][C:9]=2[CH2:15][CH3:16])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 5

HCID 24437Sodium SulfiteHCID 25517Ammonium ChlorideHCID 159087TriacetoxyperiodinaneHCID 86646397Methyl 4-{[cyclohexyl(2-ethyl-5-formylthiophen-3-yl)methyl]amino}benzoateHCID 178420663HCID 178420663, compound2×

Product 1

HCID 68515565Methyl 4-({cyclohexyl[2-ethyl-5-(2-methylpropanoyl)thiophen-3-yl]methyl}amino)benzoateYield 60%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 4-{[cyclohexyl(2-ethyl-5-formylthiophen-3-yl)methyl]amino}benzoate (400 mg) synthesized above in tetrahydrofuran (10 mL) was added dropwise 1.0M isopropylmagnesium bromide-tetrahydrofuran solution (1.25 mL) at 0° C., and the mixture was stirred for 1 hr under a nitrogen atmosphere. 1.0M Isopropylmagnesium bromide-tetrahydrofuran solution (1.25 mL) was added dropwise again, and the mixture was further stirred at 0° C. for 1 hr. Saturated aqueous ammonium chloride solution was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by NH-silica gel column chromatography (ethyl acetate) to give a yellow oil. To a solution of the obtained oil in methylene chloride (10 mL) was added Dess-Martin reagent (662 mg) at 0° C., and the mixture was stirred for 1 hr. Saturated aqueous sodium sulfite solution was added to quench the reaction, methylene chloride was evaporated using evaporator, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (15% ethyl acetate/hexane) to give the title compound (268 mg, 60%) as a pale-yellow oil.

Workup

  1. stirringthe mixture was further stirred at 0° C. for 1 hr
  2. customto quench
  3. customthe reaction
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe extract was washed with saturated brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by NH-silica gel column chromatography (ethyl acetate)
  9. customto give a yellow oil
  10. stirringthe mixture was stirred for 1 hr
  11. customto quench
  12. customthe reaction, methylene chloride
  13. customwas evaporated
  14. customevaporator
  15. extractionthe mixture was extracted with ethyl acetate
  16. washThe extract was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine
  17. dry with materialdried over magnesium sulfate
  18. concentrationconcentrated under reduced pressure
  19. customThe residue was purified by silica gel column chromatography (15% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-0f974c1a7b494e36903fb9a8763586c6
Source dataset
uspto-grants-2012_11
Patent number
US08309580B2

Reaction notes

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