Pyrrolidine → 6-Bromo-2-(2,2-dimethyltetrahydropyran-4-yl)chroman-4-one

HRID 539279Notes

Reaction equation

HRID 539279 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.[CH3:12][C:13]1([CH3:21])[CH2:18][CH:17]([CH:19]=O)[CH2:16][CH2:15][O:14]1.N1CCCC1>CO>[Br:1][C:2]1[CH:7]=[C:6]2[C:5](=[CH:4][CH:3]=1)[O:11][CH:19]([CH:17]1[CH2:16][CH2:15][O:14][C:13]([CH3:21])([CH3:12])[CH2:18]1)[CH2:9][C:8]2=[O:10]

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 959915'-Bromo-2'-hydroxyacetophenoneHCID 122319282,2-Dimethyloxane-4-carbaldehyde

Product 1

HCID 584239026-Bromo-2-(2,2-dimethyltetrahydropyran-4-yl)chroman-4-oneYield 76.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 1-(5-bromo-2-hydroxyphenyl)ethanone (13.5 g, 62.78 mmol), 2,2-dimethyltetrahydro-2H-pyran-4-carbaldehyde (9.40 g, 62.78 mmol) and pyrrolidine (5.22 mL, 62.78 mmol) in MeOH (125 mL) was heated to reflux for 3 h. The mixture was allowed to reach r.t. and then concentrated. The residue was dissolved in EtOAc (100 mL) and washed with 1M NaOH (60 mL), 1M HCl (60 mL), and brine (60 mL) successively. The organic phase was concentrated and the residue was purified by flash chromatography with a gradient of 10% EtOAc in heptane to 40% EtOAc in heptane to give the title compound (16.22 g, 76% yield): 1H NMR (500 MHz, DMSO-d6) δ ppm 1.15 (m, 6 H), 1.26 (m, 2 H), 1.52 (m, 1 H), 1.76 (m, 1 H), 2.12 (ddd, 1 H), 2.65 (m, 1 H), 2.83 (m, 1 H), 3.57 (m, 1 H), 3.66 (m, 1 H), 4.32 (ddd, 1 H), 7.05 (dd, 1 H), 7.70 (dd, 1 H), 7.78 (d, 1 H); MS (ES−) m/z 337 [M−H]−.

Workup

  1. temperatureto reflux for 3 h
  2. customto reach r.t.
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in EtOAc (100 mL)
  5. washwashed with 1M NaOH (60 mL), 1M HCl (60 mL), and brine (60 mL) successively
  6. concentrationThe organic phase was concentrated
  7. customthe residue was purified by flash chromatography with a gradient of 10% EtOAc in heptane to 40% EtOAc in heptane

Sources & evidence

ORD record
ord-572e4e38df16465b9bc7d16cf6062cbc
Source dataset
uspto-grants-2014_10
Patent number
US08865911B2

Reaction notes

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