Methyl iodide → HCID 21270058, compound

HRID 1194361Notes

Reaction equation

HRID 1194361 reaction equation
[CH2:1]([Li])CCC.C(NC(C)C)(C)C.[CH3:13][C:14]1[N:15]([CH2:19][CH2:20][C:21]([C:23]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[N:25]([CH3:32])[CH:24]=2)=[O:22])[CH:16]=[CH:17][N:18]=1.IC>C1COCC1.CN(C)P(N(C)C)(N(C)C)=O>[CH3:1][CH:20]([CH2:19][N:15]1[CH:16]=[CH:17][N:18]=[C:14]1[CH3:13])[C:21]([C:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[N:25]([CH3:32])[CH:24]=1)=[O:22]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 7912DiisopropylamineHCID 21270031HCID 21270031, compoundHCID 178418339Butyllithium

Product 1

HCID 21270058HCID 21270058, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 12679HexamethylphosphoramideSolvent

Procedure

n-Butyllithium (1.6M in hexane; 10 ml) was added dropwise to a stirred solution of diisopropylamine (1.6 ml) in dry THF (40 ml) at 0° under nitrogen. After 40 min at 0° the reaction was cooled to -70° and treated dropwise with a solution of 3-(2-methyl-1H-imidazol-1-yl)-1-(1-methyl-1H-indol-3-yl)-1-propanone (2.7 g) in dry THF (150 ml) over 45 min. After a further 30 min a solution of iodomethane (0.7 ml) in hexamethylphosphoramide (1.5 ml) was added, and the suspension was allowed to warm to room temperature over 2.5 h. The suspension was partitioned between sodium carbonate (2N; 150 ml) and ethyl acetate (2×100 ml). The combined organic extracts were dried and evaporated in vacuo to give an oil which was purified by column chromatography eluting with System B to give the free base of the title compound as an oil (2.05 g). A sample (0.5 g) of the free base was dissolved in absolute ethanol (5 ml) acidified with ethanolic hydrogen chloride, and the salt was precipitated by diluting with excess dry ether (ca. 200 ml). The salt was filtered off, and dried in vacuo to give the title compound (0.25 g), m.p. 205°-207°.

Workup

  1. temperatureAfter 40 min at 0° the reaction was cooled to -70°
  2. customThe suspension was partitioned between sodium carbonate (2N; 150 ml) and ethyl acetate (2×100 ml)
  3. customThe combined organic extracts were dried
  4. customevaporated in vacuo
  5. customto give an oil which
  6. customwas purified by column chromatography
  7. washeluting with System B

Sources & evidence

ORD record
ord-3e4214455f804b9e92c398d12f1b1050
Source dataset
uspto-grants-1989_03
Patent number
US04814344

Reaction notes

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