Methyl iodide → (R)-tert-Butyl 3-methoxypiperidine-1-carboxylate

HRID 389647Notes

Reaction equation

HRID 389647 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([OH:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:17]I>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([O:14][CH3:17])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 1514398(R)-1-Boc-3-hydroxypiperidine

Product 1

HCID 67155503(R)-tert-Butyl 3-methoxypiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To commercially available (R)-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (4.5 g, 22.36 mmol) in 60 ml DMF at 0° C. was added NaH (1.3 g, 33.54 mmol, 55-65 in mineral oil) under stirring in three portions under an argon atmosphere. After 20 min methyl iodide (4.76 g, 33.54 mmol) was added and the reaction was warmed to RT and stirred for another 3 h. After quenching with sat. aq NaHCO3-solution the mixture was extracted with ethyl acetate. The organic layer was washed with 1N KHSO4 and brine. The organic layer was dried with MgSO4, filtered and evaporated. The crude material was purified by chromatography on silica gel. Yield: 4.6 g, 96

Workup

  1. stirringstirred for another 3 h
  2. customAfter quenching with sat. aq NaHCO3-solution the mixture
  3. extractionwas extracted with ethyl acetate
  4. washThe organic layer was washed with 1N KHSO4 and brine
  5. dry with materialThe organic layer was dried with MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude material was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-77ab5b10d8f7401294e939460bbe276e
Source dataset
uspto-grants-2013_02
Patent number
US08378092B2

Reaction notes

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