Methyl iodide → (3r,4r)-Rel-tert-butyl 4-azido-3-methoxypiperidine-1-carboxylate

HRID 1593460Notes

Reaction equation

HRID 1593460 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]([N:14]=[N+:15]=[N-:16])[C@H:10]([OH:17])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].I[CH3:19].[H-].[Na+]>C1COCC1>[N:14]([C@@H:11]1[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][C@H:10]1[O:17][CH3:19])=[N+:15]=[N-:16]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 58745530(3R*,4R*)-4-azido-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 58745528(3r,4r)-Rel-tert-butyl 4-azido-3-methoxypiperidine-1-carboxylateYield 92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of 146A (320 mg, 1.32 mmol) and iodomethane (0.25 mL, 3.96 mmol) in 4 mL of dry THF at room temperature under nitrogen was added 95% NaH (40.0 mg. 1.58 mmol). This mixture was stirred at room temperature for 15 h and then quenched by addition of 30 mL of water. The aqueous solution was extracted with EtOAc (2×40 mL). The combined EtOAc extracts were washed with brine (30 mL), dried (MgSO4), filtered and concentrated in vacuo to give 310 mg (Yield: 92%) of 247A. It had an analytical HPLC retention time=2.86 min. (Phenomenox S5 C18-HC 4.6×50 mm column, 10-90% aqueous methanol over 4 minutes containing 0.1% TFA, 4 ml/min, monitoring at 220 nm) and a LC/MS M++Na=279.

Workup

  1. customquenched by addition of 30 mL of water
  2. extractionThe aqueous solution was extracted with EtOAc (2×40 mL)
  3. washThe combined EtOAc extracts were washed with brine (30 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-021dd2ed825442fd981a72d683bbf425
Source dataset
uspto-grants-2007_11
Patent number
US07297695B2

Reaction notes

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