Methyl iodide → Bexlosteride

HRID 1901988Notes

Reaction equation

HRID 1901988 reaction equation
[CH3:1]I.[Cl:3][C:4]1[CH:18]=[CH:17][C:7]2[C@@H:8]3[C@@H:13]([CH2:14][CH2:15][C:6]=2[CH:5]=1)[NH:12][C:11](=[O:16])[CH2:10][CH2:9]3.[OH-].[Na+]>C1COCC1>[Cl:3][C:4]1[CH:18]=[CH:17][C:7]2[C@@H:8]3[C@@H:13]([CH2:14][CH2:15][C:6]=2[CH:5]=1)[N:12]([CH3:1])[C:11](=[O:16])[CH2:10][CH2:9]3

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 14798Sodium HydroxideHCID 100599928-Chloro-1,4,4a,5,6,10b-hexahydro-2H-benzo[f]quinolin-3-one

Product 1

HCID 166562BexlosterideYield 142.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a 1-liter flask equipped with a condenser and a stirrer were added 470 mL of THF, 18.7 g of methyl iodide and 47 g of (4aR)-(10bR)-8-chloro-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolin-3-one, and stirring was begun at ambient temperature. To the mixture was added 100 ml of 50% aqueous sodium hydroxide in one portion, and gentle heating was begun. The temperature was raised as high as 41° and was then gradually lowered to 29° at the end of 16 hours of stirring. HPLC liquid chromatography, eluting with 1:1 acetonitrile:aqueous buffer (5% ammonium acetate) and monitoring at 220 nanometers, then showed that all the starting material had been consumed and the aqueous layer was removed. The organic layer was concentrated to an oil under vacuum, and the residue was dissolved in ethyl acetate. The solution was washed with brine, and the organic layer was washed with 200 mL of water twice, and was dried over magnesium sulfate and evaporated under vacuum while heptane was added portionwise as the ethyl acetate was removed. A total of 500 mL of heptane was added, and the product began to crystallize when about half of it had been added. The slurry was concentrated to about 300 ml, and filtered, and the solids were washed with heptane and dried in vacuum at 40°-50° to obtain 47.03 g of product, m.p. 97°-99°, of 98.7% purity.

Workup

  1. customTo a 1-liter flask equipped with a condenser and a stirrer
  2. customwas begun at ambient temperature
  3. temperaturegentle heating
  4. temperatureThe temperature was raised as high as 41°
  5. customwas then gradually lowered to 29° at the end of 16 hours
  6. stirringof stirring
  7. washHPLC liquid chromatography, eluting with 1:1 acetonitrile
  8. customhad been consumed
  9. customthe aqueous layer was removed
  10. concentrationThe organic layer was concentrated to an oil under vacuum
  11. dissolutionthe residue was dissolved in ethyl acetate
  12. washThe solution was washed with brine
  13. washthe organic layer was washed with 200 mL of water twice
  14. dry with materialwas dried over magnesium sulfate
  15. customevaporated under vacuum while heptane
  16. additionwas added portionwise as the ethyl acetate
  17. customwas removed
  18. additionA total of 500 mL of heptane was added
  19. customto crystallize when about half of it
  20. additionhad been added
  21. concentrationThe slurry was concentrated to about 300 ml
  22. filtrationfiltered
  23. washthe solids were washed with heptane
  24. customdried in vacuum at 40°-50°

Sources & evidence

ORD record
ord-f2116081c9784fa2aa8b8cd62ee3e771
Source dataset
uspto-grants-1996_11
Patent number
US05578724

Reaction notes

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