Sodium hydride → HCID 19823659, compound

HRID 1650977Notes

Reaction equation

HRID 1650977 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH:12]([N:17]([CH3:19])[CH3:18])[CH2:13][CH2:14][CH2:15][OH:16])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[H-].[Na+].ClCC(N1[CH2:31][CH2:30][O:29]CC1)=O.[CH3:32][Li].[Cl-].[NH4+]>O1CCCC1.CCOCC.O.CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([CH:12]([N:17]([CH3:19])[CH3:18])[CH2:13][CH2:14][CH2:15][O:16][CH2:32][C:30](=[O:29])[CH3:31])[CH2:9][CH2:10][CH2:11]2)=[CH:6][CH:7]=1

Participants

10

Reactant 5

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 74040Morpholine, 4-(chloroacetyl)-HCID 19823648HCID 19823648, compoundHCID 178418348HCID 178418348, compound

Product 1

HCID 19823659HCID 19823659, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent3×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of the product of Example 142 (28.1 g) in tetrahydrofuran (60 ml) was added under argon to a stirred suspension of sodium hydride (5.04 g of a 50% dispersion in mineral oil) in tetrahydrofuran (30 ml) at <30° C. After 45 minutes dimethylformamide (10 ml) was added the mixture stirred for 16 hours at ambient temperature. The mixture was cooled to below 10° C. and a solution of chloroacetylmorpholine (18 g) in tetrahydrofuran (60 ml) added. The mixture was then stirred at ambient temperature for 21/2 days and then poured into water. The aqueous mixture was extracted with ether and the extract dried and evaporated to give a residue which was distilled. The residue after distillation was dissolved in hot petroleum ether (bp 80° to 100° C.), treated with charcoal, filtered and cooled. The supernatant was decanted from an oily residue and evaporated to give an oil which was distilled on a Buchi Kugelrohr apparatus (140°/0.2 mm) leaving 2-{4-[1-(4-chlorophenyl)cyclobutyl]-4-dimethylaminobutoxy}-N,N-3-oxapentamethyleneacetamide as the residue. A solution of this product (4.18 g) in ether (20 ml) was added dropwise over 15 minutes under argon to a stirred mixture of ether (10 ml) and a 1.55M solution of methyllithium in ether (7 ml) at -20° to -25° C. The mixture was stirred for 3 hours at ambient temperature and then cooled to below -20° C. and a saturated aqueous solution of ammonium chloride (40 ml) was added. The ether phase was separated, dried and evaporated to give an oil which was purified by flash chromatography using ether as the eluant to give 1-{4-[1-(4-chlorophenyl)cyclobutyl] -4-dimethylaminobutoxy}propan-2-one as an oil the boiling point of which was not determined.

Workup

  1. temperatureThe mixture was cooled to below 10° C.
  2. stirringThe mixture was then stirred at ambient temperature for 21/2 days
  3. extractionThe aqueous mixture was extracted with ether
  4. customthe extract dried
  5. customevaporated
  6. customto give a residue which
  7. distillationwas distilled
  8. distillationThe residue after distillation
  9. dissolutionwas dissolved in hot petroleum ether (bp 80° to 100° C.)
  10. additiontreated with charcoal
  11. filtrationfiltered
  12. temperaturecooled
  13. customThe supernatant was decanted from an oily residue
  14. customevaporated
  15. customto give an oil which
  16. distillationwas distilled on a Buchi Kugelrohr apparatus (140°/0.2 mm)
  17. customleaving 2-{4-[1-(4-chlorophenyl)cyclobutyl]-4-dimethylaminobutoxy}-N,N-3-oxapentamethyleneacetamide as the residue
  18. customat -20° to -25° C
  19. stirringThe mixture was stirred for 3 hours at ambient temperature
  20. temperaturecooled to below -20° C.
  21. customThe ether phase was separated
  22. customdried
  23. customevaporated
  24. customto give an oil which
  25. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-c2b7af826ef9424ab5d7e606ff4e9d4c
Source dataset
uspto-grants-1990_05
Patent number
US04925879

Reaction notes

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