Methyl iodide → HCID 86627060, compound

HRID 505797Notes

Reaction equation

HRID 505797 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH2:13][O:14][CH3:15])[C:11]3[CH:16]=[C:17]([C:19]([OH:21])=[O:20])[S:18][C:10]=3[C:9]=2[CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)=[CH:4][CH:3]=1.[Li]CCCC.CN(CCN(C)C)C.[C:41]([O-:44])([O-])=O.[K+].[K+].[CH3:47]I>C1COCC1.CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH2:13][O:14][CH3:15])[C:11]3[C:16]([CH:41]=[O:44])=[C:17]([C:19]([O:21][CH3:47])=[O:20])[S:18][C:10]=3[C:9]=2[CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 6328Methyl iodideHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 11430Potassium CarbonateHCID 68469838HCID 68469838, compoundHCID 178418339Butyllithium

Product 1

HCID 86627060HCID 86627060, compoundYield 72%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

A solution (0.27 M) of 5-(4-chlorophenyl)-6-cyclohexyl-4-(methoxymethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylic acid in THF was added dropwise to a solution of n-BuLi (3 eq.) and TMEDA (3 eq.) in THF (50 mL) at −78° C. The reaction mixture was stirred at −78° C. for 1.5 h then the resulting solution was treated with DMF (10 eq.). The mixture was stirred at −78° C. for 2 h, then quenched with aqueous NH4Cl (saturated solution), quickly diluted with AcOEt and poured into aqueous HCl (1 N). The aqueous layer was separated and extracted with AcOEt. The combined organic phase was dried and concentrated under vacuum. The resulting residue was azeotropically dried by co-evaporation with toluene, giving a crude that was dissolved in DMF. The resulting solution (0.22 M) was treated with K2CO3 (1.5 eq.) and MeI (5 eq.). The mixture was stirred at RT overnight then diluted with AcOEt and washed with water and brine. Evaporation of the solvent under reduced pressure afforded a residue that was purified by flash chromatography on silica gel (1:9 AcOEt/petroleum ether and AcOEt) to afford the title compound (72%) as a solid.

Workup

  1. stirringThe mixture was stirred at −78° C. for 2 h
  2. customquenched with aqueous NH4Cl (saturated solution)
  3. additionquickly diluted with AcOEt
  4. additionpoured into aqueous HCl (1 N)
  5. customThe aqueous layer was separated
  6. extractionextracted with AcOEt
  7. customThe combined organic phase was dried
  8. concentrationconcentrated under vacuum
  9. dry with materialThe resulting residue was azeotropically dried by co-evaporation with toluene
  10. customgiving a crude that
  11. stirringThe mixture was stirred at RT overnight
  12. washwashed with water and brine
  13. customEvaporation of the solvent under reduced pressure
  14. customafforded a residue that
  15. customwas purified by flash chromatography on silica gel (1:9 AcOEt/petroleum ether and AcOEt)

Sources & evidence

ORD record
ord-cf8f14e0621c4bf99fd0c471db5398e3
Source dataset
uspto-grants-2010_08
Patent number
US07781431B2

Reaction notes

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