Methyl iodide → HCID 18009397, compound

HRID 987589Notes

Reaction equation

HRID 987589 reaction equation
[C:1]([C:4]1[CH:5]=[C:6](C(OC)=O)[C:7]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][C:11]=2[O:18][CH3:19])=[CH:8][CH:9]=1)(=[O:3])C.[Li+].CC([N-][CH:29]([CH3:31])[CH3:30])C.[CH3:32]I.[C:34]([O-:37])(O)=[O:35].[Na+]>COCCOC>[CH3:19][O:18][C:11]1[CH:12]=[C:13]([O:16][CH3:17])[CH:14]=[CH:15][C:10]=1[C:7]1[C:8]([C:34]([O:37][CH3:32])=[O:35])=[CH:9][C:4]([C:1](=[O:3])[CH:29]([CH3:30])[CH3:31])=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 6328Methyl iodide2×HCID 516892Sodium BicarbonateHCID 2724682Lithium diisopropylamide2×HCID 11324480HCID 11324480, compound

Product 1

HCID 18009397HCID 18009397, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
-20 °C

Procedure

The compound from step B (1.03 g, 3.2 mmol) was dissolved in DME (40 ml) under argon and cooled to −20° C. and LDA (1.6 ml, 3.2 mmol) was added. The mixture was then warmed to room temperature and stirred for 30 min. Methyl iodide (0.2 ml, 3.2 mmol) was slowly added over 15 min. to give a cloudy suspension. The mixture was again cooled to −20 C. and a second portion of LDA (1.6 ml, 3.2 mmol) was added. After the mixture was warmed to room temperature and stirred for 30 min a second portion of methyl iodide (0.2 ml, 3.2 mmol) was added and the mixture stirred for 60 h. The mixture was added to cold NaHCO3 (100 ml) and extracted with ethyl acetate (3×100 ml). The organic layer was washed with 5% HCl (3×25 ml) then dried and evaporated. The residue was chromatographed on silica gel with hexane/ethyl acetate (2:1) to give 0.208 g (24%) of the title compound. 1H-NMR (400 MHz, CDCl3) δH 1.24 (6H, t, CH(CH3)2), 3.60 (1H, m, CH(CH3)2, 3.71 (3H, s, OCH3), 3.89 (3H, s, OCH3), 3.93 (3H, s, OCH3), 6.86-8.32 (6H, ArH).

Workup

  1. temperatureThe mixture was then warmed to room temperature
  2. customto give a cloudy suspension
  3. temperatureThe mixture was again cooled to −20 C
  4. temperatureAfter the mixture was warmed to room temperature
  5. additionwas added
  6. stirringthe mixture stirred for 60 h
  7. extractionextracted with ethyl acetate (3×100 ml)
  8. washThe organic layer was washed with 5% HCl (3×25 ml)
  9. customthen dried
  10. customevaporated
  11. customThe residue was chromatographed on silica gel with hexane/ethyl acetate (2:1)

Sources & evidence

ORD record
ord-500f62a164b24e348541cc849e12c082
Source dataset
uspto-grants-2003_10
Patent number
US06632835B2

Reaction notes

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