2,3-Dihydrofuran → (2-Bromo-3-methylphenyl)(4,5-dihydrofuran-2-yl)methanone

HRID 1028945Notes

Reaction equation

HRID 1028945 reaction equation
[O:1]1[CH:5]=[CH:4][CH2:3][CH2:2]1.C([Li])CCC.[Br:11][C:12]1[C:17]([CH3:18])=[CH:16][CH:15]=[CH:14][C:13]=1[C:19](N1CCOCC1)=[O:20]>C1COCC1.CCOCC>[Br:11][C:12]1[C:17]([CH3:18])=[CH:16][CH:15]=[CH:14][C:13]=1[C:19]([C:5]1[O:1][CH2:2][CH2:3][CH:4]=1)=[O:20]

Participants

6

Reactant 3

HCID 709342,3-DihydrofuranHCID 712534814-(2-Bromo-3-methylbenzoyl)morpholineHCID 178418339Butyllithium

Product 1

HCID 67324982(2-Bromo-3-methylphenyl)(4,5-dihydrofuran-2-yl)methanone

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2,3-dihydrofuran (0.70 mL, 9.25 mmol) in THF (9.0 mL) under inert atmosphere was cooled to −78° C. A solution of n-butyllithium, 1.7 M in pentanes (5.98 mL, 10.17 mmol), was added dropwise over 10 min. The reaction was maintained at that temperature for 30 min, and allowed to warm to 0° C. for 30 min. It was cooled back down to −78° C. and then added via cannula to a solution of (2-bromo-3-methylphenyl)(morpholino)methanone (2.02 g, 7.12 mmol) in Et2O (17.92 mL), also at −78° C. The solution was stirred at that temperature for 10 min and then allowed to warm to 0° C. The mixture was partitioned between Et2O and water and the organics were washed with water and brine. The solution was dried over Na2SO4 and concentrated. The crude material was absorbed onto a plug of silica gel and purified by column chromatography eluting with a gradient of Et2O in hexane, to provide (2-bromo-3-methylphenyl)(4,5-dihydrofuran-2-yl)methanone as a colorless oil. This oil was immediately re-dissolved in Et2O and placed under nitrogen before storing in the freezer for further use.

Workup

  1. temperatureThe reaction was maintained at that temperature for 30 min
  2. temperatureIt was cooled back down to −78° C.
  3. temperatureto warm to 0° C
  4. customThe mixture was partitioned between Et2O and water
  5. washthe organics were washed with water and brine
  6. dry with materialThe solution was dried over Na2SO4
  7. concentrationconcentrated
  8. customThe crude material was absorbed onto a plug of silica gel
  9. custompurified by column chromatography
  10. washeluting with a gradient of Et2O in hexane

Sources & evidence

ORD record
ord-f8f6164be2cf4f5eb06ea4707e4cc208
Source dataset
uspto-grants-2014_05
Patent number
US08735384B2

Reaction notes

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