Hydrochloric Acid → HCID 19699366, compound

HRID 471806Notes

Reaction equation

HRID 471806 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[C:7](=O)[CH2:6][CH2:5]2.[N:13](OCCC(C)C)=O.Cl.O>CO>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[CH2:7][CH:6]([NH2:13])[CH2:5]2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 8053Isoamyl NitriteHCID 117689445,6-Difluoro-1-indanone

Product 1

HCID 19699366HCID 19699366, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 5,6-difluoro-2,3-dihydro-1H-inden-1-one (4.60 g, 27.4 mmol) in MeOH (90 mL) at 40° C. was added isoamyl nitrite (4.17 g, 35.6 mmol) followed by concentrated HCl (2.7 mL). Upon heating for 45 min the solution was cooled to room temperature and water was added. Precipitated solid was collected by filtration and rinsed thoroughly with water affording 3.97 g of a light orange solid. The solid was dissolved in HOAc (100 mL), conc HCl (8 mL) was added, followed by 10% Pd/C (1.07 g). The mixture was hydrogenated under 50 psi H2 for 24 hr using a Parr hydrogenation apparatus, and filtered through a bed of Celite (CHCl3 wash). The filtrate was concentrated in vacuo and the residue was dissolved in water. The aqueous solution was basified with solid K2CO3, extracted with CHCl3 (3×), combined extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography (MeOH/CH2Cl2) affording the title compound as a brown oil. 1H NMR (400 MHz, CDCl3) δ 6.95 (t, 2H, J=8.9 Hz), 3.83 (m, 1H), 3.10 (dd, 2H, J=15.8 & 6.8 Hz), 2.60 (dd, 2H, J=15.8 & 5.0 Hz); (M+H) 170, 0.68 min (LC/MS method A).

Workup

  1. temperatureUpon heating for 45 min the solution
  2. customPrecipitated solid
  3. filtrationwas collected by filtration
  4. washrinsed thoroughly with water affording 3.97 g of a light orange solid
  5. dissolutionThe solid was dissolved in HOAc (100 mL)
  6. additionconc HCl (8 mL) was added
  7. filtrationfiltered through a bed of Celite (CHCl3 wash)
  8. concentrationThe filtrate was concentrated in vacuo
  9. dissolutionthe residue was dissolved in water
  10. extractionextracted with CHCl3 (3×)
  11. dry with materialwere dried over MgSO4
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by flash chromatography (MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-42381d7a6c0f4aa2be5de187dd3c0a87
Source dataset
uspto-grants-2014_01
Patent number
US08633175B2

Reaction notes

Loading…