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

HRID 1877267Notes

Reaction equation

HRID 1877267 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]1([Mg]Br)[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1.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]([CH:28]3[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]3)=[O:14])[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 178420632HCID 178420632, compound

Product 1

HCID 68508125Methyl 4-({cyclohexyl[5-(cyclohexylcarbonyl)-2-ethylthiophen-3-yl]methyl}amino)benzoateYield 57%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 4-{[cyclohexyl(2-ethyl-5-formylthiophen-3-yl)methyl]amino}benzoate (500 mg) synthesized in Example 287 (6) in tetrahydrofuran (10 mL) was added dropwise 1.0M cyclohexylmagnesium bromide-tetrahydrofuran solution (3.25 mL) at −45° C., and the mixture was stirred 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 to give a yellow oil. To a solution of the obtained oil in methylene chloride (10 mL) was added Dess-Martin reagent (827 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 (20% ethyl acetate/hexane) to give the title compound (347 mg, 57%) as a pale-brown oil.

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customto give a yellow oil
  8. stirringthe mixture was stirred for 1 hr
  9. customto quench
  10. customthe reaction, methylene chloride
  11. customwas evaporated
  12. customevaporator
  13. extractionthe mixture was extracted with ethyl acetate
  14. washThe extract was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine
  15. dry with materialdried over magnesium sulfate
  16. concentrationconcentrated under reduced pressure
  17. customThe residue was purified by silica gel column chromatography (20% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-4b716dbf644f4d5eaf56be680471ecc7
Source dataset
uspto-grants-2012_11
Patent number
US08309580B2

Reaction notes

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