Acetic Acid → 1-Methyl-4-phenylpiperidine-4-carbonitrile

HRID 1800811Notes

Reaction equation

HRID 1800811 reaction equation
[C:1]1([C:7]2([C:13]#[N:14])[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C=O.[C:17](O[BH-](OC(=O)C)OC(=O)C)(=O)C.C(O)(=O)C>CN(C)C=O.COC(OC)OC.Cl>[CH3:17][N:10]1[CH2:9][CH2:8][C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)([C:13]#[N:14])[CH2:12][CH2:11]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 1811384-Piperidinecarbonitrile, 4-phenyl-HCID 2724942Triacetoxyborohydride

Product 1

HCID 625131-Methyl-4-phenylpiperidine-4-carbonitrileYield 86.5%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 86600666DMF trimethylorthoformateSolvent

Conditions

Temperature
23 °C

Procedure

4-Phenylpiperidine-4-carbonitrile (1.35 g, 6.062 mmol) was dissolved in N,N-dimethylformamide/trimethylorthoformate (1:1, 12 mL) and treated with paraformaldehyde (0.596 mL, 18.19 mmol), triacetoxyborohydride (3.854 g, 18.185 mmol) and acetic acid (1 mL). The mixture was stirred at 23° C. overnight, then diluted with 1N hydrochloric acid and washed with ethyl acetate. The aqueous phase was basified with aqueous sodium bicarbonate and extracted with ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated to give the title material (1.05 g, 50%) as an oil. LC/MS (M+H)+: 200. HPLC ret. time (Condition B): 1.315 min. 1H NMR (400 MHz, CDCl3) δ ppm: 2.10-2.21 (4H, m), 2.41 (3H, s), 2.53 (2H, td, J=11.81, 3.41 Hz), 2.99 (2H, d, J=12.38 Hz), 7.32-7.38 (1H, m), 7.39-7.45 (2H, m), 7.49-7.54 (2H, m).

Workup

  1. washwashed with ethyl acetate
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-98cf00fe16954366936ec96e30a0759e
Source dataset
uspto-grants-2013_01
Patent number
US08343999B2

Reaction notes

Loading…