4-Piperidinol, 1-methyl- → 6-[(1-Methylpiperidin-4-yl)oxy]pyridine-2-carbonitrile

HRID 2239336Notes

Reaction equation

HRID 2239336 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([OH:8])[CH2:4][CH2:3]1.Br[C:10]1[N:15]=[C:14]([C:16]#[N:17])[CH:13]=[CH:12][CH:11]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>C1(C)C=CC=CC=1.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([O:8][C:10]2[N:15]=[C:14]([C:16]#[N:17])[CH:13]=[CH:12][CH:11]=2)[CH2:4][CH2:3]1

Participants

7

Reactant 3

HCID 660484-Piperidinol, 1-methyl-HCID 27342152-(Di-tert-butylphosphino)biphenylHCID 151008596-Bromopyridine-2-carbonitrile

Product 1

HCID 645945946-[(1-Methylpiperidin-4-yl)oxy]pyridine-2-carbonitrileYield 45.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

1-Methylpiperidin-4-ol (1.89 g, 0.0164 mol), 6-bromo-2-pyridinecarbonitrile (3.00 g, 0.0164 mol), Pd(OAc)2 (0.184 g, 0.820 mmol), 2-(di-t-butylphosphino)biphenyl (0.303 g, 1.02 mmol) and Cs(CO3)2 were mixed in 100 mL of toluene. The reaction mixture was stirred under argon and heated to 130° C. in an oil bath for 4 days. The reaction mixture was diluted with EtOAc and washed with water, dried over Na2SO4 and evaporated. The crude product was flash chromatographed on silica gel DCM/MeOH/TEA 95/5/1 to give 1.62 g (45%) of the desired product. 1H NMR (500 MHz, CDCl3) δ 7.67 (m, 1H), 7.29 (d, 1H), 6.95 (d, 1H), 5.12 (m, 1H), 2.74 (m, 2H), 2.40-2.30 (m, 5H, thereof a singlet at 2.35), 2.09 (m, 2H), 1.86 (m, 2H).

Workup

  1. washwashed with water
  2. dry with materialdried over Na2SO4
  3. customevaporated
  4. customchromatographed on silica gel DCM/MeOH/TEA 95/5/1

Sources & evidence

ORD record
ord-945b105ffa8747b0b4d91681225ac05e
Source dataset
uspto-grants-2010_05
Patent number
US07723331B2

Reaction notes

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