Ethyl bromoacetate → Ethyl 1-benzyloxycarbonylpiperidine-4-oxyacetate

HRID 2357053Notes

Reaction equation

HRID 2357053 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([OH:17])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23]>O1CCOCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([O:17][CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 2794620Benzyl 4-Hydroxy-1-piperidinecarboxylate

Product 1

HCID 23370004Ethyl 1-benzyloxycarbonylpiperidine-4-oxyacetate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

The compound of example 67a (16 g; 70 mmol) in dioxane (25 ml) was added drop wise at 5-10° C. to (toluene washed) 55% NaH (3.84 g; 80 mmol) suspended in dioxane (25 ml) over a period of 30 min. in an atmosphere of nitrogen. The reaction mixture was stirred at room temperature for 1 h, cooled to 0° C. and treated to a drop wise addition of ethyl 2-bromoacetate (8.9 ml; 80 58 mmol) over a period of 15-20 min. It was poured over crushed ice, and extracted with EtOAc. The EtOAc layer was washed with brine, dried (Na2SO4), concentrated and purified using flash chromatography (silica gel, 5-10% CH3CN in chloroform). Yield, 18.5 g (84.55%), oil; MS (ESI): 344 (M++Na), 322 (M++1).

Workup

  1. temperaturecooled to 0° C.
  2. additionIt was poured
  3. customover crushed ice
  4. extractionextracted with EtOAc
  5. washThe EtOAc layer was washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. custompurified
  9. customYield

Sources & evidence

ORD record
ord-a62a043604b84f08a7b6ec9d34ebaeee
Source dataset
uspto-grants-2010_07
Patent number
US07759387B2

Reaction notes

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