Hydrochloric Acid → 8-bromo-3-(N-methylcyclopropyl-N-n-propylamino)chroman

HRID 1464701Notes

Reaction equation

HRID 1464701 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[O:10][CH2:9][CH:8]([NH:12][CH2:13][CH2:14][CH3:15])[CH2:7]2.[CH:16]1(C(Cl)=O)[CH2:18][CH2:17]1.[BH4-].[CH2:23]([N+](CCCC)(CCCC)CCCC)CCC.Cl.[OH-].[Na+]>ClCCl.C([O-])([O-])=O.[Na+].[Na+].ClCCCl>[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[O:10][CH2:9][CH:8]([N:12]([CH3:23])[CH2:13][CH2:14][CH2:15][CH:16]1[CH2:18][CH2:17]1)[CH2:7]2

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 77637Cyclopropanecarbonyl chlorideHCID 169536Tetrabutylammonium borohydrideHCID 190871638-Bromo-3-(n-propylamino)chroman

Product 1

HCID 678531698-bromo-3-(N-methylcyclopropyl-N-n-propylamino)chromanYield 61.7%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent2×HCID 10340Sodium CarbonateSolvent

Procedure

To a mixture of 8-bromo-3-(n-propylamino)chroman (120 mg; 0.5 mmol) in dichloromethane (20 ml) and 5% aqueous Na2CO3 (20 ml) was added cyclopropanecarbonyl chloride (300 mg; 3.5 mmol). The mixture was stirred for 2 hours, the phases were separated and the organic layer dried (MgSO4). The solvent was evaporated and the crude amide was reduced with tetrabutylammonium borohydride (500 mg, 2.0 mmol) in a boiling (1:1)-mixture (50 ml) of dichloromethane and 1,2-dichloroethane for 24 hours. Hydrochloric acid (1M; 10 ml) was added and the phases were stirred for 1 hour at room temperature. pH was adjusted with 2M aqueous NaOH to 11 add the phases were separated. The organic layer was dried (Na2SO4) and the solvent evaporated yielding an oil, which was chromatographed (SiO2) eluting with light petroleum:ether (3:1). The fractions containing pure product were pooled yielding 100 mg (61%) of 8-bromo-3-(N-methylcyclopropyl-N-n-propylamino)chroman. GC/MS showed M+ /M+2 at m/e=323 (11%)/325 (10% and the base peak pair m/e=294(110%)/296(98%).

Workup

  1. customthe phases were separated
  2. dry with materialthe organic layer dried (MgSO4)
  3. customThe solvent was evaporated
  4. stirringthe phases were stirred for 1 hour at room temperature
  5. additionadd the phases
  6. customwere separated
  7. dry with materialThe organic layer was dried (Na2SO4)
  8. customthe solvent evaporated
  9. customyielding an oil, which
  10. customwas chromatographed (SiO2)
  11. washeluting with light petroleum:ether (3:1)
  12. additionThe fractions containing pure product

Sources & evidence

ORD record
ord-d72c50f3bd1d4cbc8cc2f18e0778d53e
Source dataset
uspto-grants-1994_04
Patent number
US05306830

Reaction notes

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