4-Methoxypiperidine → HCID 117602079, compound

HRID 1477107Notes

Reaction equation

HRID 1477107 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[CH3:12][O:13][CH:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.C(O[Na])(C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[CH3:12][O:13][CH:14]1[CH2:19][CH2:18][N:17]([C:2]2[CH:11]=[CH:10][CH:9]=[C:8]3[C:3]=2[CH:4]=[CH:5][N:6]=[CH:7]3)[CH2:16][CH2:15]1

Participants

6

Reactant 3

HCID 776664-MethoxypiperidineHCID 7364875-BromoisoquinolineHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 117602079HCID 117602079, compoundYield 52.4%

Reagents, catalysts & solvents 2

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
85 °C

Procedure

To 5-bromoisoquinoline (10.40 g, 50 mmol), 4-methoxypiperidine (4.92 mL, 50.0 mmol), Pd2(dba)3 (0.458 g, 0.500 mmol), BINAP (0.934 g, 1.500 mmol), and t-BuONa (6.73 g, 70.0 mmol) was added degassed toluene (60 mL) and the reaction was heated, under N2, to 85° C. for 24 h and then to 105° C. for 3 h. The reaction mixture was cooled to ambient temperature and water was added. The phases were separated and the aqueous layer extracted three times with ethyl acetate. The combined organics were washed with brine, dried (Na2SO4), filtered and purified by silica gel chromatography to afford 6.34 g (52.4%) of Intermediate 3A as a pale yellow solid. MS (ESI) m/z: 243.2 (M+H)+.

Workup

  1. customdegassed toluene (60 mL)
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. additionwater was added
  4. customThe phases were separated
  5. extractionthe aqueous layer extracted three times with ethyl acetate
  6. washThe combined organics were washed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-8972c0a21bb544b8a8287e1a9ef98651
Source dataset
uspto-grants-2016_08
Patent number
US09403774B2

Reaction notes

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