63463-36-5 → HCID 13141172, compound

HRID 1701709Notes

Reaction equation

HRID 1701709 reaction equation
[Br:1][C:2]1[CH:16]=[CH:15][C:5]2[CH:6]=[CH:7][N:8]3[CH:14]=[CH:13][CH:12]=[C:9]3[C:10](=[O:11])[C:4]=2[CH:3]=1.[CH3:17][N:18]1[CH2:23][CH2:22][CH-:21][CH2:20][CH2:19]1.[Mg+2].[Cl-]>O1CCCC1>[CH3:17][N:18]1[CH2:23][CH2:22][CH:21]([C:10]2([OH:11])[C:4]3[CH:3]=[C:2]([Br:1])[CH:16]=[CH:15][C:5]=3[CH:6]=[CH:7][N:8]3[CH:14]=[CH:13][CH:12]=[C:9]23)[CH2:20][CH2:19]1

Participants

4

Reactant 2

HCID 1092077663463-36-5HCID 13141170HCID 13141170, compound

Product 1

HCID 13141172HCID 13141172, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of 9-bromo-11H-pyrrolo[2,1-b][3]benzazepine-11-one (10.0 g., 0.036 mole) in 100 ml dry tetrahydrofuran, under a nitrogen atmosphere, is stirred in an ice bath. A solution of 1-methylpiperidine-4-magnesium chloride in tetrahydrofuran (76 ml, 0.51 M, 0.039 mole) is added dropwise. Upon completion of addition the solution is allowed to stir at room temperature for one hour after which time the solvent is removed on a film evaporator. The residue is dissolved in 300 ml benzene, the solution stirred and treated with a solution containing one gram of ammonium chloride in 10 ml H2O. After one hour the mixture is filtered and the filter cake washed three times with 100 ml portions of boiling benzene. Upon evaporation of the combined filtrates in vacuo, the residue is chromatographed over a column of 400 g of silica gel packed with chloroform. A non-polar impurity is eluted with chloroform and thereafter the eluant is changed to 2%, then 5% methanol in chloroform. A second contaminant is eluted prior to the product fractions. The product fractions are combined and evaporated to give crude 1-methyl-4-(9-bromo-11-hydroxy-11H-pyrrolo[2,1-b][3]benzazepin-11-yl)piperidine (8.8 g, 65%). The crude product is used directly in the next step without further purification.

Workup

  1. additionUpon completion of addition the solution
  2. stirringto stir at room temperature for one hour after which time the solvent
  3. customis removed on a film evaporator
  4. dissolutionThe residue is dissolved in 300 ml benzene
  5. stirringthe solution stirred
  6. additiontreated with a solution
  7. additioncontaining one gram of ammonium chloride in 10 ml H2O
  8. filtrationAfter one hour the mixture is filtered
  9. washthe filter cake washed three times with 100 ml portions of boiling benzene
  10. customUpon evaporation of the combined filtrates in vacuo
  11. customthe residue is chromatographed over a column of 400 g of silica gel
  12. washA non-polar impurity is eluted with chloroform
  13. washA second contaminant is eluted
  14. customevaporated

Sources & evidence

ORD record
ord-2420212d5d1e4935857fea78225653d5
Source dataset
uspto-grants-1980_03
Patent number
US04195091

Reaction notes

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