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

HRID 327236Notes

Reaction equation

HRID 327236 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([S:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[C:8]([CH2:12][C:13]([CH3:19])([CH3:18])[C:14]([O:16][CH3:17])=[O:15])[NH:9]2)=[CH:5][CH:4]=1.[CH3:25][Si]([N-][Si](C)(C)C)(C)C.[K+].IC>C1COCC1.CN(P(N(C)C)(N(C)C)=O)C.C1(C)C=CC=CC=1>[CH3:25][N:9]1[C:10]2[C:6](=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[CH:11]=2)[C:7]([S:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[C:8]1[CH2:12][C:13]([CH3:19])([CH3:18])[C:14]([O:16][CH3:17])=[O:15]

Participants

7

Reactant 3

HCID 6328Methyl iodideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 53636575Methyl 3-[6-methoxy-3-(t-butylthio) indol-2-yl]-2,2-dimethylpropanoate

Product 1

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

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 12679HexamethylphosphoramideSolvent

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 HCl (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 HCl (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-d688306480fd4054b5398cd2397616b0
Source dataset
uspto-grants-1993_12
Patent number
US05272145

Reaction notes

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