Dimethyl malonate → 2-(4-Bromo-pyridin-2-ylmethyl)-malonic acid dimethyl ester

HRID 336346Notes

Reaction equation

HRID 336346 reaction equation
[C:1]([O:8][CH3:9])(=[O:7])[CH2:2][C:3]([O:5][CH3:6])=[O:4].[H-].[Na+].[Br:12][C:13]1[CH:18]=[CH:17][N:16]=[C:15]([CH2:19]Cl)[CH:14]=1.[NH4+].[Cl-]>C1COCC1.C(Cl)Cl>[CH3:6][O:5][C:3](=[O:4])[CH:2]([CH2:19][C:15]1[CH:14]=[C:13]([Br:12])[CH:18]=[CH:17][N:16]=1)[C:1]([O:8][CH3:9])=[O:7]

Participants

7

Reactant 4

HCID 7943Dimethyl malonateHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 533020224-Bromo-2-(chloromethyl)pyridine

Product 1

HCID 683858902-(4-Bromo-pyridin-2-ylmethyl)-malonic acid dimethyl esterYield 57%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of dimethyl malonate (3.83 g) in dry THF (10 mL) at 0° C. was added NaH (463 mg) and the reaction mixture was stirred at rt for 30 min. A solution of 4-bromo-2-chloromethyl-pyridine (1.99 g) in dry THF (10 mL) was added and the reaction mixture stirred at rt for 15 h. It was then diluted with DCM, treated with a sat. aq. NH4Cl solution and the org. layers were washed with water and brine, dried over MgSO4, filtered and concentrated under reduced pressure. The title compound was obtained, after purification by CC (Hept/EA 100:0 to 50:50), as a yellow oil (1.65 g; 57% yield).

Workup

  1. stirringthe reaction mixture stirred at rt for 15 h
  2. washlayers were washed with water and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-df256ccca2b5409183cecbd8d86998eb
Source dataset
uspto-grants-2014_11
Patent number
US08889676B2

Reaction notes

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