Ethyl bromoacetate → Ethyl 1-benzyloxycarbonylpiperidine-4-oxyacetate

HRID 2425034Notes

Reaction equation

HRID 2425034 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-bed58ede8f364c0495c080f061f92088
Source dataset
uspto-grants-2011_06
Patent number
US07964628B2

Reaction notes

Loading…