Triethylamine → 3-[4-(2-Bromo-5-fluorophenoxy)piperidin-1-yl]isoxazole-5-carbonitrile

HRID 561209Notes

Reaction equation

HRID 561209 reaction equation
[Br:1][C:2]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:15]=[C:14]([C:16]([NH2:18])=O)[O:13][N:12]=2)[CH2:7][CH2:6]1.CCN(CC)CC.C(OC(C(F)(F)F)=O)(C(F)(F)F)=O>C(Cl)Cl>[Br:1][C:2]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:15]=[C:14]([C:16]#[N:18])[O:13][N:12]=2)[CH2:7][CH2:6]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 533885293-[4-(2-Bromo-5-fluorophenoxy)piperidin-1-yl]isoxazole-5-carboxamide

Product 1

HCID 533885303-[4-(2-Bromo-5-fluorophenoxy)piperidin-1-yl]isoxazole-5-carbonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 3-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]isoxazole-5-carboxamide (1.6 g, 4.2 mmol) and Et3N (1.5 mL, 10.8 mmol) in CH2Cl2 (20 mL) was added TFAA (0.8 mL, 5.7 mmol) at ice-water bath temperature. A homogeneous solution resulted. After addition, the cooling bath was removed and the mixture was stirred at room temperature for 2 h. The mixture was quenched with water (10-15 mL), followed by saturated aqueous NaHCO3 (15-20 mL) and extracted with CH2Cl2 (2×30 mL). The combined CH2Cl2 extracts were washed with diluted brine (40 mL), dried (Na2SO4) and concentrated. Chromatography over silica gel and elution with hexanes:EtOAc (4:1) gave the title compound as a colorless gum.

Workup

  1. customA homogeneous solution resulted
  2. additionAfter addition
  3. customthe cooling bath was removed
  4. customThe mixture was quenched with water (10-15 mL)
  5. extractionextracted with CH2Cl2 (2×30 mL)
  6. washThe combined CH2Cl2 extracts were washed with diluted brine (40 mL)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. washChromatography over silica gel and elution with hexanes:EtOAc (4:1)

Sources & evidence

ORD record
ord-11528afec91e475b8df732a2970c3f15
Source dataset
uspto-grants-2011_11
Patent number
US08063224B2

Reaction notes

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