Water → 6-Bromo-2',4',5',6'-tetrahydrospiro[chroman-2,3'-pyran]-4-one

HRID 1965041Notes

Reaction equation

HRID 1965041 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([C:8](=[O:10])[CH3:9])[CH:7]=1.[O:12]1[CH2:17][CH2:16][CH2:15][C:14](=O)[CH2:13]1.N1CCCC1.O>C1(C)C=CC=CC=1.CCOC(C)=O>[Br:1][C:2]1[CH:7]=[C:6]2[C:5](=[CH:4][CH:3]=1)[O:11][C:14]1([CH2:15][CH2:16][CH2:17][O:12][CH2:13]1)[CH2:9][C:8]2=[O:10]

Participants

7

Reactant 4

HCID 962WaterHCID 31268PyrrolidineHCID 901092H-Pyran-3(4H)-one, dihydro-2×HCID 959915'-Bromo-2'-hydroxyacetophenone

Product 1

HCID 584238236-Bromo-2',4',5',6'-tetrahydrospiro[chroman-2,3'-pyran]-4-oneYield 79.4%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1-(5-bromo-2-hydroxyphenyl)ethanone (8.2 g, 38.13 mmol), dihydro-pyran-3-one (4.96 g, 49.57 mmol) and pyrrolidine (4.12 mL, 49.57 mmol) in toluene (80 mL) was stirred at 50° C. for 1 h. The temperature was increased to reflux, and the reaction was refluxed for 22 h. Additional dihydro-pyran-3-one (0.5 g 5 mmol) was added and the mixture was refluxed for an additional 24 h. The mixture was allowed to reach r.t., and then water (50 mL) followed by EtOAc (100 mL) was added. The organic layer was concentrated and the residue was purified by flash chromatography using a gradient of heptane to 40% EtOAc in heptane to give the title compound (9 g, 79% yield): 1H NMR (500 MHz, CDCl3) δ ppm 1.57 (m, 1 H), 1.72 (ddd, 1 H), 1.96 (m, 1 H), 2.12 (m, 1 H), 2.71 (m, 2 H), 3.51 (d, 1 H), 3.58 (m, 1 H), 3.86 (m, 2 H), 6.96 (d, 1 H), 7.57 (dd, 5 H), 7.97 (d, 4 H); MS (ES+) m/z 297 [M+H]+.

Workup

  1. temperatureThe temperature was increased
  2. temperatureto reflux
  3. temperaturethe reaction was refluxed for 22 h
  4. temperaturethe mixture was refluxed for an additional 24 h
  5. customto reach r.t.
  6. additionwas added
  7. concentrationThe organic layer was concentrated
  8. customthe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-f6d6a5b459b54ad1ae712bcd74dc500f
Source dataset
uspto-grants-2013_04
Patent number
US08415483B2

Reaction notes

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