Methyl iodide → HCID 22633405, compound

HRID 2416918Notes

Reaction equation

HRID 2416918 reaction equation
[H-].[K+].[Cl:3][C:4]1[CH:5]=[C:6]([C:10]2([CH:17](C)[OH:18])[CH2:15][CH2:14][N:13]([CH3:16])[CH2:12][CH2:11]2)[CH:7]=[CH:8][CH:9]=1.[CH3:20]I.[K]>CCCCCC.O1CCCC1.CN(C)C=O.C(Cl)(Cl)Cl.O.CO>[Cl:3][C:4]1[CH:5]=[C:6]([C:10]2([CH2:17][O:18][CH3:20])[CH2:15][CH2:14][N:13]([CH3:16])[CH2:12][CH2:11]2)[CH:7]=[CH:8][CH:9]=1

Participants

11

Reactant 4

HCID 6328Methyl iodideHCID 82127Potassium hydrideHCID 5462222PotassiumHCID 9878248HCID 9878248, compound

Product 1

HCID 22633405HCID 22633405, compoundYield 97%

Reagents, catalysts & solvents 6

HCID 887MethanolSolventHCID 962WaterSolventHCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

Potassium hydride oil suspension (3.80 g of 35%; 33 mmoles) was washed with hexane, 15 mL of tetrahydro-furan was added, and the suspension was treated with 4.25 g (16 mmoles) of 4-(3′-chlorophenyl)-α, 1-dimethyl-4-piperidinemethanol (Example 1) dissolved in 15 mL of tetrahydrofuran. The mixture was stirred at room temperature for 1 hour; methyl iodide (9.1 g, 64 mmoles) was added which caused the temperature to rise to 50° C. Methanol (5 mL) was added after stirring for 2.75 hours, keeping the temperature below 25° C. Water and chloroform were added, and the mixture was filtered to remove 4.70 g of the methiodide of the title compound. This solid was combined with the products obtained on removal of the solvent from the chloroform layer, and heated with 7.0 g of potassium methylmercaptide in 30 mL of dimethyl formamide in an 80° C. oil bath for 2.5 hours. The solvent was removed, water was added to the residue and the mixture was extracted with methylene chloride. Removal of the solvent from the dried extracts and short-path distillation of the residue (130° C. bath temperature, 1 micron) gave 3.94 g (88% yield) of the title compound as an oil. 1H NMR (CDCl3): δ 7.2-7.4 (m,4H); 3.3 (s,3H); 3.2 (quartet, J=7 Hz,1H); 2.7 (m,2H); 2.2 (s,3H); 1.8-2.4 (m,6H); and 0.9 (d,J=7 Hz,3H). High resolution mass spectrum: m/e calcd. for C15H22ClNO: 267.1390; measured: 267.1393.

Workup

  1. additionwas added
  2. customto rise to 50° C
  3. stirringafter stirring for 2.75 hours
  4. customthe temperature below 25° C
  5. filtrationthe mixture was filtered
  6. customto remove 4.70 g of the methiodide of the title compound
  7. customobtained on removal of the solvent from the chloroform layer
  8. customThe solvent was removed
  9. additionwater was added to the residue
  10. extractionthe mixture was extracted with methylene chloride
  11. customRemoval of the solvent
  12. distillationfrom the dried extracts and short-path distillation of the residue (130° C. bath temperature, 1 micron)

Sources & evidence

ORD record
ord-4d5f31e2a94d4e12b40f6dc78a0c2265
Source dataset
uspto-grants-2004_11
Patent number
US06825217B2

Reaction notes

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