p-Bromochlorobenzene → (2R)-4'-chloro-2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propiophenone

HRID 2396998Notes

Reaction equation

HRID 2396998 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][CH:3]=1.[Mg].[O:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH:11]1[O:16][C@H:17]([CH3:26])[C:18](N1CCOCC1)=[O:19].[Cl-].[NH4+]>O1CCCC1.O>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([C:18](=[O:19])[C@H:17]([O:16][CH:11]2[CH2:12][CH2:13][CH2:14][CH2:15][O:10]2)[CH3:26])=[CH:3][CH:4]=1

Participants

7

Reactant 4

HCID 7806p-Bromochlorobenzene2×HCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 10977653(2R)-1-morpholino-2-((tetrahydro-2H-pyran-2-yl)oxy)propan-1-one

Product 1

HCID 10445767(2R)-4'-chloro-2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propiophenoneYield 235.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 1-bromo-4-chlorobenzene (20 g) in tetrahydrofuran (260 ml) was added magnesium (turnings, 7.47 g). The mixture was vigorously stirred at room temperature. When the temperature of the mixture reached 40° C., the reaction vessel was cooled in a water bath. A solution of 1-bromo-4-chlorobenzene (38.9 g) in tetrahydrofuran (90 ml), was added dropwise to the mixture at 34°-40° C., followed by stirring for an hour at 30° C. To the mixture was added dropwise a solution of 4-[(2R)-2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propionyl]morpholine (60 g) in tetrahydrofuran (60 ml) over the period of 15 minutes at 0° C. The mixture was stirred for 3 hours at room temperature. To the reaction mixture were added a saturated aqueous ammonium chloride solution (120 ml) and water (100 ml). The mixture was extracted with ethyl acetate (500 ml). The organic layer was washed with water, dried over magnesium sulfate and distilled under reduced pressure. The residue was purified by silica gel column chromatography (silica gel 900 g, eluent: hexane/ethyl acetate=30:1→10:1) to give (2R)-4'-chloro-2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propiophenone (66 g) as a pale yellow oily substance.

Workup

  1. customreached 40° C.
  2. temperaturethe reaction vessel was cooled in a water bath
  3. stirringby stirring for an hour at 30° C
  4. stirringThe mixture was stirred for 3 hours at room temperature
  5. extractionThe mixture was extracted with ethyl acetate (500 ml)
  6. washThe organic layer was washed with water
  7. dry with materialdried over magnesium sulfate
  8. distillationdistilled under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (silica gel 900 g, eluent: hexane/ethyl acetate=30:1→10:1)

Sources & evidence

ORD record
ord-781c3009ea624f0f8ef7387bd1a0707d
Source dataset
uspto-grants-1996_02
Patent number
US05495024

Reaction notes

Loading…