Methyl iodide → 1-[(Tert-butoxy)carbonyl]-4-methoxypiperidine-4-carboxylic acid

HRID 1949077Notes

Reaction equation

HRID 1949077 reaction equation
C([O:3][C:4]([C:6]1([OH:19])[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1)=[O:5])C.[H-].[Na+].I[CH3:23].O[Li].O>CN(C=O)C.O>[C:15]([O:14][C:12]([N:9]1[CH2:8][CH2:7][C:6]([O:19][CH3:23])([C:4]([OH:3])=[O:5])[CH2:11][CH2:10]1)=[O:13])([CH3:16])([CH3:17])[CH3:18]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 168937Lithium hydroxide, monohydrateHCID 577788811-tert-Butyl 4-ethyl 4-hydroxypiperidine-1,4-dicarboxylate

Product 1

HCID 457917301-[(Tert-butoxy)carbonyl]-4-methoxypiperidine-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

A mixture of 0.415 g (1.52 mmol) 4-Hydroxy-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester, 68 mg (1.97 mmol) NaH (55% in oil) and 0.3 g (2.12 mmol) iodomethane in 10 mL DMF was stirred for 2 h at room temperature. Water was added and the mixture was concentrated to dryness. The residue was dissolved in THF and water and 0.254 g (6 mmol) LiOH.H2O wad added and the mixture was stirred for 16 h at room temperature. After evaporation the residue was subjected to purification by preparative HPLC on reversed phase eluting with a gradient formed from acetonitrile, water and formic acid to yield after evaporation of the product containing fractions 49.7 mg (13%) of the title compound as white solid. MS (m/e): 258.1 [(M−H)].

Workup

  1. concentrationthe mixture was concentrated to dryness
  2. dissolutionThe residue was dissolved in THF
  3. stirringthe mixture was stirred for 16 h at room temperature
  4. customAfter evaporation the residue
  5. customwas subjected to purification by preparative HPLC on reversed phase
  6. washeluting with a gradient
  7. customformed from acetonitrile, water and formic acid
  8. customto yield
  9. customafter evaporation of the product
  10. additioncontaining fractions 49.7 mg (13%) of the title compound as white solid

Sources & evidence

ORD record
ord-13c0bcc5fec2427d8eb33964d2f16df8
Source dataset
uspto-grants-2013_03
Patent number
US08399676B2

Reaction notes

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