p-Toluenesulfonic acid → tert-Butyl 2-bromo-7,9-dimethyl-5,7,8,9-tetrahydro-6H-pyrido[3',4':4,5]pyrrolo[2,3-b]pyridine-6-carboxylate

HRID 882055Notes

Reaction equation

HRID 882055 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N:8]([CH3:10])N)[N:3]=1.[CH3:11][CH:12]1[CH2:17][C:16](=O)[CH2:15][CH2:14][N:13]1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20].C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+].C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O>CCO.O.C(O)(C)C>[Br:1][C:2]1[N:3]=[C:4]2[N:8]([CH3:10])[C:16]3[CH2:17][CH:12]([CH3:11])[N:13]([C:19]([O:21][C:22]([CH3:23])([CH3:25])[CH3:24])=[O:20])[CH2:14][C:15]=3[C:5]2=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 11430Potassium CarbonateHCID 90495Di-tert-butyl dicarbonateHCID 12992764tert-Butyl 2-methyl-4-oxopiperidine-1-carboxylateHCID 575147632-Bromo-6-(1-methylhydrazinyl)pyridine

Product 1

HCID 86667082tert-Butyl 2-bromo-7,9-dimethyl-5,7,8,9-tetrahydro-6H-pyrido[3',4':4,5]pyrrolo[2,3-b]pyridine-6-carboxylateYield 11.9%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
160 °C

Procedure

2-Bromo-6-(1-methylhydrazinyl)pyridine (1.60 g, 7.98 mmol) and tert-butyl 2-methyl-4-oxopiperidine-1-carboxylate (enantiomer B) (1.70 g, 7.98 mmol) were heated in EtOH (10 mL) at reflux for 16 h and then the mixture was concentrated to provide a white foam. This foam was combined with para-toluenesulphonic acid (3.18 g, 16.7 mmol) and heated to 160° C. for 10 minutes. The mixture was allowed to cool and isopropanol (20 mL), water (8 mL), potassium carbonate (5.00 g, 36.2 mmol), and di-tert-butyl dicarbonate (2.55 g, 11.7 mmol) were added. After stirring for 16 h, the mixture was partitioned between methylene chloride and water, and the organic layer was removed, dried, and concentrated. The residue was purified by column chromatography eluting with ethyl acetate/hexanes (1:4) to provide the title compound (360 mg, 11%) as a white solid: ESI MS m/z 380 [M+H]+.

Workup

  1. temperatureat reflux for 16 h
  2. concentrationthe mixture was concentrated
  3. customto provide a white foam
  4. temperatureto cool
  5. customthe mixture was partitioned between methylene chloride and water
  6. customthe organic layer was removed
  7. customdried
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography
  10. washeluting with ethyl acetate/hexanes (1:4)

Sources & evidence

ORD record
ord-d2f9e9471058423d8191c1c85113bb8e
Source dataset
uspto-grants-2015_03
Patent number
US08993765B2

Reaction notes

Loading…