Pyridine → 4-(1-(4-Bromophenyl)piperidin-4-yl)morpholine

HRID 472304Notes

Reaction equation

HRID 472304 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([N:7]2[CH2:12][CH2:11][O:10][CH2:9][CH2:8]2)[CH2:3][CH2:2]1.[Br:13][C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][CH:15]=1.N1C=CC=CC=1.ClCCl>O>[Br:13][C:14]1[CH:19]=[CH:18][C:17]([N:1]2[CH2:6][CH2:5][CH:4]([N:7]3[CH2:12][CH2:11][O:10][CH2:9][CH2:8]3)[CH2:3][CH2:2]2)=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 6344DichloromethaneHCID 79599(4-Bromophenyl)boronic acidHCID 7957244-Morpholinopiperidine

Product 1

HCID 667303494-(1-(4-Bromophenyl)piperidin-4-yl)morpholine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A round bottom flask equipped with a drying tube was charged with 4-piperidin-4-yl-morpholine (0.21 g, 1.2 mmol), cupric acetate (0.34 g, 1.9 mmol), 4-bromobenzeneboronic acid (0.50 g, 2.5 mmol), pyridine (0.20 mL, 2.5 mmol) and dichloromethane (5 mL, 80 mmol). The blue suspension was stirred open to the air for 6 days at room temperature. Water (25 mL) was added to the green-brown suspension and stirred for 10 minutes. The mixture was extracted with ethyl acetate (3×25 mL). The combined organic layer was washed with saturated aqueous sodium chloride (25 mL), dried over magnesium sulfate, filtered and evaporated. The residue was purified via chromatography using silica gel column (40 g) and 0%→8% methanol: dichloromethane solvent gradient. 4-[1-(4-Bromo-phenyl)-piperidin-4-yl]-morpholine was isolated as a tan solid (0.168 g, 41%). MP=146-149° C. 1H NMR (400 MHz, CDCl3, δ, ppm): 7.32 (d, J=7.5 Hz, 2H), 6.79 (d, J=7.8 Hz, 2H), 3.76-3.71 (m, 4H), 3.68 (d, J=12.8 Hz, 2H), 2.71 (t, J=12.3 Hz, 2H), 2.60-2.54 (m, 4H), 2.37-2.27 (m, 1H), 1.93 (d, J=11.3 Hz, 2H), 1.69-1.58 (m, 2H). MS=325, 327 (MH)+.

Workup

  1. customA round bottom flask equipped with a drying tube
  2. stirringstirred for 10 minutes
  3. extractionThe mixture was extracted with ethyl acetate (3×25 mL)
  4. washThe combined organic layer was washed with saturated aqueous sodium chloride (25 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified via chromatography

Sources & evidence

ORD record
ord-dc2c566ab46f4d9794302418707b233d
Source dataset
uspto-grants-2014_01
Patent number
US08633173B2

Reaction notes

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