Methyl iodide → Methyl 3-[N-methyl-3-(t-butylthio)-6-methoxyindol-2-yl]-2,2-dimethylpropanoate

HRID 1769354Notes

Reaction equation

HRID 1769354 reaction equation
C[CH:2]([C:9]1NC2[C:16]([C:17]=1[S:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[CH:15][CH:14]=[C:13]([O:23][CH3:24])[CH:12]=2)[C:3]([CH3:8])([CH3:7])[C:4]([OH:6])=[O:5].C[Si]([N-][Si](C)(C)C)(C)C.[K+].I[CH3:36].CN(P([N:45]([CH3:47])[CH3:46])(N(C)C)=O)C>C1COCC1.C1(C)C=CC=CC=1>[CH3:46][N:45]1[C:47]2[C:16](=[CH:15][CH:14]=[C:13]([O:23][CH3:24])[CH:12]=2)[C:17]([S:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[C:9]1[CH2:2][C:3]([CH3:8])([CH3:7])[C:4]([O:6][CH3:36])=[O:5]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 12679HexamethylphosphoramideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 54438884Methyl 3-[6-methoxy-3-(t-butylthio) indol-2-yl]-2,2-dimethylpropanoic acid

Product 1

HCID 18947604Methyl 3-[N-methyl-3-(t-butylthio)-6-methoxyindol-2-yl]-2,2-dimethylpropanoate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1.75 g of the indole from Step A in 30 mL of THF and 3 mL HMPA was cooled to -78° C. and to this solution was slowly added a solution of 0.54M KHMDS in toluene (10.2 mL). The mixture was stirred at this temperature for 15 min. and treated with 0.34 mL of iodomethane. The mixture was stirred at -78° C. for 5 h, quenched with 1N HC1 (100 mL), extracted with ethyl acetate, and the organic layer washed with H2O, dried over Na2SO4 and evaporated to dryness. The residue was chromatographed on flash silica gel using ethyl acetate:hexane (20:80) as eluant to afford the title compound as a solid; m.p. 97-98° C.

Workup

  1. stirringThe mixture was stirred at -78° C. for 5 h
  2. customquenched with 1N HC1 (100 mL)
  3. extractionextracted with ethyl acetate
  4. washthe organic layer washed with H2O
  5. dry with materialdried over Na2SO4
  6. customevaporated to dryness
  7. customThe residue was chromatographed on flash silica gel

Sources & evidence

ORD record
ord-a1e55bf3467c44e49f35021a8b9ade97
Source dataset
uspto-grants-1995_01
Patent number
US05380850

Reaction notes

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