Methyl iodide → (Rac)-(3r,4r)-4-azido-3-methoxy-piperidine-1-carboxylic acid benzyl ester

HRID 1676598Notes

Reaction equation

HRID 1676598 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C@@H:14]([N:17]=[N+:18]=[N-:19])[C@H:13]([OH:20])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].I[CH3:24].[Cl-].[NH4+]>O1CCCC1.CN(C)C=O>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C@@H:14]([N:17]=[N+:18]=[N-:19])[C@H:13]([O:20][CH3:24])[CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 58745456n-Carbobenzoxy-trans-3-hydroxy-4-azidopiperidine

Product 1

HCID 90891592(Rac)-(3r,4r)-4-azido-3-methoxy-piperidine-1-carboxylic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

To a mixture of 0.150 g (0.54 mmole) of (rac)-(3R,4R)-4-azido-3-hydroxy-piperidine-1-carboxylic acid benzyl ester in 3.75 mL of tetrahydrofuran-dimethylformamide (4:1) at 0 degrees, was added 0.026 g of sodium hydride (60% mineral oil dispersion). After stirring for 10 minutes, 0.060 mL of iodomethane was added. The mixture was warmed to room temperature, stirred for 2 hours, then cooled in an ice-bath, and 1 mL of saturated aqueous ammonium chloride solution added. The resulting mixture was partitioned between 50 mL of ethyl acetate and 50 mL of saturated aqueous ammonium chloride solution. The organic layer was successively with water, then brine and dried over anhydrous magnesium sulfate. The mixture was filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatoraphy, eluting with hexanes-ethyl acetate (85:15) to give 0.085 g of (rac)-(3R,4R)-4-azido-3-methoxy-piperidine-1-carboxylic acid benzyl ester as a colorless oil.

Workup

  1. stirringstirred for 2 hours
  2. temperaturecooled in an ice-bath
  3. customThe resulting mixture was partitioned between 50 mL of ethyl acetate and 50 mL of saturated aqueous ammonium chloride solution
  4. dry with materialbrine and dried over anhydrous magnesium sulfate
  5. filtrationThe mixture was filtered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatoraphy
  8. washeluting with hexanes-ethyl acetate (85:15)

Sources & evidence

ORD record
ord-1c97de6c17114ab38508ef551bce5b51
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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