1,4-Difluorobenzene → HCID 66849804, compound

HRID 1160678Notes

Reaction equation

HRID 1160678 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][CH:3]=1.N1([C:15](=[O:25])[C@@H:16]([O:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)[CH3:17])CCOCC1.C(NC(C)C)(C)C.[Li]>C1COCC1.C1COCC1.CCCCCCC>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:15](=[O:25])[C@@H:16]([O:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1)[CH3:17]

Participants

6

Reactant 3

HCID 108921,4-DifluorobenzeneHCID 14978394HCID 14978394, compoundHCID 45051747Lithium diisopropylamine

Product 1

HCID 66849804HCID 66849804, compoundYield 46.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21263495Tetrahydrofuran heptaneSolvent

Conditions

Temperature
0 °C

Procedure

1,4-Difluorobenzene (1.8 g; 15.8 mmol) and (2S)-1-Morpholin-4-yl-2-(tetrahydro-pyran-2-yloxy)-propan-1-one (3 g; 10.5 mmol) are dissolved in dry THF (15 ml). The mixture is cooled to 0° C. and then lithium diisopropylamine (7.9 ml of a 2M solution in THF/Heptane; 15.8 mmol) is added dropwise over a period of 20 minutes. The mixture is stirred for another 2 hours at 0° C. The reaction is then quenched with a saturated ammonium chloride solution. The reaction mixture is extracted with ethyl acetate. The organic phase is washed with water and brine and then dried over magnesium sulfate. The solids are filtered off and the solvent is removed under reduced pressure. The crude product is chromatographed over silicagel (eluent:Petrol ether/Ethyl acetate 50:1 to 30:1). 1.31 g of yellow crystalline material (yield 44.8%) is obtained with a HPLC purity of 96.2%.

Workup

  1. addition15.8 mmol) is added dropwise over a period of 20 minutes
  2. customThe reaction is then quenched with a saturated ammonium chloride solution
  3. extractionThe reaction mixture is extracted with ethyl acetate
  4. washThe organic phase is washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationThe solids are filtered off
  7. customthe solvent is removed under reduced pressure
  8. customThe crude product is chromatographed over silicagel (eluent:Petrol ether/Ethyl acetate 50:1 to 30:1)

Sources & evidence

ORD record
ord-9e596690b3e24b7ba9296892aecce392
Source dataset
uspto-grants-2010_10
Patent number
US07816537B2

Reaction notes

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