Trimethyl orthoformate → 1-Acetyl-4,4-dimethoxy-piperidine

HRID 2196092Notes

Reaction equation

HRID 2196092 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8]C(=O)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[CH:11]([O:16][CH3:17])([O:14][CH3:15])OC>CO.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C[O-].[Na+]>[C:1]([N:4]1[CH2:9][CH2:8][C:11]([O:14][CH3:15])([O:16][CH3:17])[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

6

Reactant 2

HCID 9005Trimethyl orthoformate2×HCID 122563N-Acetyl-4-piperidone

Product 1

HCID 126536461-Acetyl-4,4-dimethoxy-piperidineYield 89.2%

Reagents, catalysts & solvents 3

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 10942334Sodium MethoxideCatalystHCID 887MethanolSolvent2×

Procedure

A solution of 1-acetyl-4-piperidone (17.0 g, 121 mmol), trimethyl orthoformate (26.4 mL, 241 mmol) and para-toluenesulfonic acid monohydrate (80 mg, 0.42 mmol) in dry methanol (34 mL) was refluxed for one hour. Then 1.0 M methanolic NaOMe (0.42 mL, 0.42 mmol) and excess of methanol and trimethyl orthoformate were removed by distillation (atmospheric pressure). Further distillation under reduced pressure afforded 1-acetyl-4,4-dimethoxy-piperidine (20.2 g, 89%) 1H NMR (DMSO) δ 3.45-3.32 (m, 4H), 3.10 (s, 6H), 1.99 (s, 3H), 1.72-1.62 (m, 2H), 1.61-1.52 (m, 2H).

Workup

  1. distillationFurther distillation under reduced pressure

Sources & evidence

ORD record
ord-4a56d7b9dea5446f82ab7ca68dcaa477
Source dataset
uspto-grants-2012_12
Patent number
US08338431B2

Reaction notes

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