Pyrrolidine → 6-bromo-2-(tetrahydro-2H-pyran-3-yl)chroman-4-one

HRID 1408824Notes

Reaction equation

HRID 1408824 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][CH:14]([CH:18]=O)[CH2:13]1.N1CCCC1>CO>[Br:1][C:2]1[CH:7]=[C:6]2[C:5](=[CH:4][CH:3]=1)[O:11][CH:18]([CH:14]1[CH2:15][CH2:16][CH2:17][O:12][CH2:13]1)[CH2:9][C:8]2=[O:10]

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 959915'-Bromo-2'-hydroxyacetophenoneHCID 10129928Oxane-3-carbaldehyde

Product 1

HCID 584241476-bromo-2-(tetrahydro-2H-pyran-3-yl)chroman-4-oneYield 22.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 1-(5-bromo-2-hydroxyphenyl)ethanone (6.069 g, 28.23 mmol) and tetrahydro-2H-pyran-3-carbaldehyde (3.218 g, 28.23 mmol) in MeOH (50 mL) was added pyrrolidine (1.5 mL). The resulting solution was heated to reflux and monitored with LC-MS. 50% conversion was achieved after 2 h. After 12 h, there was no improvement in conversion. The reaction mixture was cooled down to room temperature and the solvent was removed under reduced pressure. The residue was purified by flash chromatography on silica gel and eluted with EA in hexane (0-30%) to produce 1.981 g of 6-bromo-2-(tetrahydro-2H-pyran-3-yl)chroman-4-one. 1.321 g of 6-bromo-2-(tetrahydro-2H-pyran-3-yl)chroman-4-one was further purified by preparative HPLC to give (S/R)-6-bromo-2-((S/R)-tetrahydro-2H-pyran-3-yl)chroman-4-one (A) (669 mg, polar isomer on preparative HPLC) and (S/R)-6-bromo-2-((R/S)-tetrahydro-2H-pyran-3-yl)chroman-4-one (B)(512 mg, less polar isomer on preparative HPLC). MS ESI+ve m/z 311 (M+H)+.

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureto reflux
  3. waitAfter 12 h
  4. customthe solvent was removed under reduced pressure
  5. customThe residue was purified by flash chromatography on silica gel
  6. washeluted with EA in hexane (0-30%)

Sources & evidence

ORD record
ord-aeb9ce78ed4c4e62b431e676b69fdd8a
Source dataset
uspto-grants-2014_12
Patent number
US08921359B2

Reaction notes

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