5-bromo-1,2-dimethyl-1H-imidazole → (1,2-Dimethyl-1H-imidazol-5-yl)(tetrahydro-2H-pyran-4-yl)methanone

HRID 926495Notes

Reaction equation

HRID 926495 reaction equation
[Li]CCCC.Br[C:7]1[N:11]([CH3:12])[C:10]([CH3:13])=[N:9][CH:8]=1.CON(C)[C:17]([CH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)=[O:18]>C1COCC1>[CH3:12][N:11]1[C:7]([C:17]([CH:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[O:18])=[CH:8][N:9]=[C:10]1[CH3:13]

Participants

5

Reactant 3

HCID 72048795-bromo-1,2-dimethyl-1H-imidazoleHCID 23144693N-methoxy-N-methyloxane-4-carboxamideHCID 178418339Butyllithium

Product 1

HCID 118006250(1,2-Dimethyl-1H-imidazol-5-yl)(tetrahydro-2H-pyran-4-yl)methanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of n-BuLi (4.0 mL, 10 mmol, 2.5 M solution in hexane) was slowly added to a solution of 5-bromo-1,2-dimethyl-1H-imidazole (1.77 g, 10.2 mmol) in THF (70 mL) at −78° C. After addition, stirring was continued for an additional 30 minutes and N-methoxy-N-methyltetrahydro-2H-pyran-4-carboxamide (1.76 g, 10.1 mmol, Intermediate 1: step a, Procedure A) dissolved in THF (25 mL) was slowly added. An additional 6 mL of THF was used to complete the quantitative addition. The mixture was stirred at −78° C. for 5 minutes then warmed to room temperature and stirred for 1 hour. The solution was quenched with water and layers were separated. The aqueous layer was extracted with DCM and the combined organic extracts washed with brine, dried over MgSO4, filtered and evaporated in vacuo. The crude product was purified using flash column chromatography (0 to 6% MeOH/DCM) to provide the title compound.

Workup

  1. additionAfter addition
  2. additionwas slowly added
  3. additionthe quantitative addition
  4. stirringThe mixture was stirred at −78° C. for 5 minutes
  5. stirringstirred for 1 hour
  6. customThe solution was quenched with water and layers
  7. customwere separated
  8. extractionThe aqueous layer was extracted with DCM
  9. washthe combined organic extracts washed with brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. customevaporated in vacuo
  13. customThe crude product was purified

Sources & evidence

ORD record
ord-01e46e9d68074936a05af789211c3e6d
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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