Methyl iodide → HCID 178484086, compound

HRID 1382935Notes

Reaction equation

HRID 1382935 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH2:12][C@H:13]1[CH2:18][CH2:17][C@H:16]([C:19]([OH:21])=[O:20])[CH2:15][CH2:14]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH3:24]I>CN(C)C=O>[CH2:1]([O:8][C:9]([N:11]([CH2:12][C@H:13]1[CH2:18][CH2:17][C@H:16]([C:19]([OH:21])=[O:20])[CH2:15][CH2:14]1)[CH3:24])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 178523389HCID 178523389, compound

Product 1

HCID 178484086HCID 178484086, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solutionoof 20.3 g (0.07 mol) of trans-4-(N-benzyloxycarbonyl-aminomethyl)cyclohexanecarboxylic acid in 380 ml of dimethylformamide is treated at 15°-20° under argon with 0.21 mol of sodium hydride (9.35 g of a 55% dispersion in mineral oil) and thereupon stirred at room temperature for a further 30 minutes. A solution of 17.5 ml (0.28 mol) of methyl iodide in 20 ml of dimethylformamide is added thereto at 25°-30° within 20 minutes and the mixture is stirred at 70° for a further 1 hour. After concentration under reduced pressure the residue is partitioned between water and methylene chloride. The organic phase is evaporated and the residual oil is dissolved in a mixture of 350 ml of ethanol and 350 ml of 1N sodium hydroxide solution. The mixture is heated to reflux for 1 hour, cooled and poured into 700 ml of ice-water The solution is extracted with ethyl acetate and then acidified with 6N hydrochloric acid. The liberated acid is extracted with methylene chloride and the extract is dried over sodium sulphate and evaporated. The residual oil is chromatographed on 270 g of silica gel with a mixture of methylene chloride/ethyl acetate (4:1) as the elution agent. There are obtained 13.6 g (64%) of trans-4-(N-benzyloxycarbonyl-N-methyl-aminomethyl)cyclohexanecarboxylic acid as a thick oil.

Workup

  1. waitat 25°-30° within 20 minutes
  2. stirringthe mixture is stirred at 70° for a further 1 hour
  3. concentrationAfter concentration under reduced pressure the residue
  4. customis partitioned between water and methylene chloride
  5. customThe organic phase is evaporated
  6. dissolutionthe residual oil is dissolved in a mixture of 350 ml of ethanol and 350 ml of 1N sodium hydroxide solution
  7. temperatureThe mixture is heated
  8. temperatureto reflux for 1 hour
  9. temperaturecooled
  10. additionpoured into 700 ml of ice-water The solution
  11. extractionis extracted with ethyl acetate
  12. extractionThe liberated acid is extracted with methylene chloride
  13. dry with materialthe extract is dried over sodium sulphate
  14. customevaporated
  15. customThe residual oil is chromatographed on 270 g of silica gel with a mixture of methylene chloride/ethyl acetate (4:1) as the elution agent

Sources & evidence

ORD record
ord-64b72c27f0334f8798f2e08984a4f49f
Source dataset
uspto-grants-1989_02
Patent number
US04808605

Reaction notes

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