Carbamic acid, ethyl-, ethyl ester → Piperidine, 1-[(4-bromo-2-ethoxyphenyl)methyl]-

HRID 1505896Notes

Reaction equation

HRID 1505896 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:16]=[CH:15][C:7]([CH2:8][N:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[C:6](F)[CH:5]=1.C(NC([O:23][CH2:24][CH3:25])=O)C>O1CCOCC1.O>[Br:3][C:4]1[CH:16]=[CH:15][C:7]([CH2:8][N:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[C:6]([O:23][CH2:24][CH3:25])[CH:5]=1

Participants

6

Reactant 3

HCID 12195Carbamic acid, ethyl-, ethyl esterHCID 24758Sodium hydrideHCID 53486112HCID 53486112, compound

Product 1

HCID 58266459Piperidine, 1-[(4-bromo-2-ethoxyphenyl)methyl]-Yield 74%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

Sodium hydride (306 mg, 60%, 7.6 mmol) was added in portions to a solution of 1-(4-bromo-2-fluorobenzyl)-piperidine (520 mg, 1.9 mmol) and ethyl urethane (0.91 mL, 7.6 mmol) in dioxane (10 mL) under an atmosphere of nitrogen. The reaction mixture was then sonicated for 30 minutes until gas evolution ceased then heated at 140° C. overnight in a sealed tube. The reaction mixture was diluted with water and extracted with DCM (3×30 mL). The combined organic layer was dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to afford a colourless oil that was then purified by flash chromatography (silica, 12 g column, ISCO, 0-10% methanol in DCM) to afford the title compound as a white solid (416 mg, 74%). 1H NMR (CDCl3, 400 MHz): 7.23 (d, J=8.1 Hz, 1H), 7.03 (dd, J=8.1, 1.9 Hz, 1H), 6.95 (d, J=1.9 Hz, 1H), 3.99 (q, J=7.0 Hz, 2H), 3.47 (s, 2H), 2.46-2.35 (m, 4H), 1.61-1.53 (m, 4H), 1.45-1.36 (m, 5H).

Workup

  1. customThe reaction mixture was then sonicated for 30 minutes until gas evolution
  2. extractionextracted with DCM (3×30 mL)
  3. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customto afford a colourless oil that
  7. customwas then purified by flash chromatography (silica, 12 g column, ISCO, 0-10% methanol in DCM)

Sources & evidence

ORD record
ord-dd09fa19466249cbacb188286af2f7b4
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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