4-Methoxypiperidine → HCID 117602079, compound

HRID 629810Notes

Reaction equation

HRID 629810 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-726ee1b1c78c474c84c7864fb8b65df1
Source dataset
uspto-grants-2016_04
Patent number
US09315519B2

Reaction notes

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