Methyl iodide → HCID 68569123, compound

HRID 1990907Notes

Reaction equation

HRID 1990907 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(=O)=O.[CH3:18]C(C)=O.[S:22]1[CH:26]=[CH:25][CH:24]=[C:23]1[Li].CI>C1COCC1>[C:4]([O:3][C:1]([N:8]1[CH2:13][CH2:12][C:11]([O:14][CH3:18])([C:23]2[S:22][CH:26]=[CH:25][CH:24]=2)[CH2:10][CH2:9]1)=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 18522661Acetone cardiceHCID 178418439HCID 178418439, compound

Product 1

HCID 68569123HCID 68569123, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-Boc-4-piperidone (Boc-29.155) (201 mg, 1.01 mmol) in THF (5 mL), cooled by dry ice/acetone, was added 2-thienyllithium (1M in THF, 1.5 mL, 1.5 mmol). After 50 min, the cooling bath was removed; after additional 1 h, methyl iodide (125 μL, 2.01 mmol) was added, and the solution was stirred at ambient temperature overnight. The solvent was evaporated, water was added, and the mixture was extracted with EtOAc (4×15 mL). The combined organic layers were washed with water and brine, dried over MgSO4, filtered and concentrated. The crude material (acc. to 1H NMR mixture of methyl ether and the alcohol in a 1:2 ratio) was methylated according to the general procedure, yielding 300 mg (1.01 mmol, 100% yield) of the title compound as yellow oil. 1H NMR (CDCl3, 200 MHz): δ=1.46 (s, 9H), 1.93 (brdt, J=4.3, 12.6 Hz, 2H), 2.00 (brd, J=12.8 Hz, 2H), 3.05 (s, 3H), 3.16 (brt, J=11.0 Hz, 2H), 3.84 (brd, J=12.2 Hz, 2H), 6.93-7.00 (m, 2H), 7.25-7.31 (m, 1H).

Workup

  1. customthe cooling bath was removed
  2. waitafter additional 1 h
  3. customThe solvent was evaporated
  4. additionwater was added
  5. extractionthe mixture was extracted with EtOAc (4×15 mL)
  6. washThe combined organic layers were washed with water and brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. additionto 1H NMR mixture of methyl ether

Sources & evidence

ORD record
ord-20c54e52841b43d58d41711b7f7ddc7a
Source dataset
uspto-grants-2010_01
Patent number
US07645754B2

Reaction notes

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