Ammonium Chloride → HCID 10264208, compound

HRID 1489422Notes

Reaction equation

HRID 1489422 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[F:8].[O:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH:10]1[O:15][C@@H:16]([CH3:25])[C:17](N1CCOCC1)=[O:18].[Mg].[Cl-].[NH4+]>O1CCCC1.O>[F:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[C:17](=[O:18])[C@@H:16]([O:15][CH:10]1[CH2:11][CH2:12][CH2:13][CH2:14][O:9]1)[CH3:25]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 612591-Bromo-2-fluorobenzene2×HCID 5462224MagnesiumHCID 14978394HCID 14978394, compound

Product 1

HCID 10264208HCID 10264208, compoundYield 103.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
35 °C

Procedure

1-Bromo-2-fluorobenzene (15 g) and 40 g of 4-[(2S)-2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propionyl]morpholine was dissolved in 200 ml of tetrahydrofuran, to which 44 g of magnesium turnings was added, and the mixture was vigorously stirred. The reaction vessel was cooled when a temperature of the reaction solution was raised to 35° C., and 16.7 g of 1-bromo-2-fluorobenzene was added dropwise to the reaction solution at 35° to 37° C. over the period of 10 minutes. After stirring at 30° to 35° C. for 2 hours, the reaction solution was ice-cooled, to which 100 ml of a saturated aqueous solution of ammonium chloride and 100 ml of water were added. The mixture was extracted with ethyl acetate (200 ml×2, 100 ml). Then, the extract was washed with water and an aqueous solution of sodium chloride successively, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by silica gel chromatography (eluent; hexane:ethyl acetate=10:1 to 5:1) to give 22.4 g of (2S)-2'-fluoro-2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propiophenone as a pale yellow oil.

Workup

  1. additionwas added
  2. temperatureThe reaction vessel was cooled when a temperature of the reaction solution
  3. stirringAfter stirring at 30° to 35° C. for 2 hours
  4. additionwere added
  5. extractionThe mixture was extracted with ethyl acetate (200 ml×2, 100 ml)
  6. washThen, the extract was washed with water
  7. dry with materialan aqueous solution of sodium chloride successively, and dried over magnesium sulfate
  8. distillationThe solvent was distilled off under reduced pressure
  9. customthe residue was purified by silica gel chromatography (eluent; hexane:ethyl acetate=10:1 to 5:1)

Sources & evidence

ORD record
ord-a7e466faa90341b1802e245c7cf7bdf8
Source dataset
uspto-grants-1997_10
Patent number
US05677464

Reaction notes

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