Methyl vinyl ketone → 5-Amino-2-butyl-6-fluoro-2-(3-oxobutyl)-1-indanone

HRID 1372510Notes

Reaction equation

HRID 1372510 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[C:7](=[O:12])[CH:6]([CH2:13][CH2:14][CH2:15][CH3:16])[CH2:5]2.C[O-:18].[Na+].[CH:20]([C:22]([CH3:24])=O)=[CH2:21]>C(O)C.C(Cl)Cl>[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[C:7](=[O:12])[C:6]([CH2:21][CH2:20][CH2:22][CH3:24])([CH2:13][CH2:14][C:15](=[O:18])[CH3:16])[CH2:5]2

Participants

6

Reactant 3

HCID 6570Methyl vinyl ketoneHCID 10942334Sodium MethoxideHCID 179727175-Amino-2-butyl-6-fluoro-1-indanone

Product 1

HCID 179727075-Amino-2-butyl-6-fluoro-2-(3-oxobutyl)-1-indanoneYield 221.9%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 5-amino-2-butyl-6-fluoro-1-indanone (0.98 g, 4.64 mmol) in ethanol (17 mL) was treated with sodium methoxide (0.5M solution in MeOH, 1.86 mL, 0.928 mmol) and methyl vinyl ketone (0.579 mL, 6.97 mmol). The resulting solution was stirred at room temperature and under a nitrogen atmosphere for 2 days. The mixture was diluted with CH2Cl2 and filtered through a pad of silica gel. The product washed off with EtOAc and the filtrate was evaporated under vacuum. The residue was purified by flash chromatography on a Biotage 40M KP-Sil column, eluting with 3:1 to 2.5:1 hexanes-EtOAc. The product containing fractions were evaporated under vacuum to provide to afford 5-amino-2-butyl-6-fluoro-2-(3-oxobutyl)-1-indanone(0.6 g, 46%) as a yellow foam.

Workup

  1. filtrationfiltered through a pad of silica gel
  2. washThe product washed off with EtOAc
  3. customthe filtrate was evaporated under vacuum
  4. customThe residue was purified by flash chromatography on a Biotage 40M KP-Sil column
  5. washeluting with 3:1 to 2.5:1 hexanes-EtOAc
  6. additionThe product containing fractions
  7. customwere evaporated under vacuum
  8. customto provide

Sources & evidence

ORD record
ord-72a918d2b67a4226bc454fc1099004af
Source dataset
uspto-grants-2007_01
Patent number
US07157604B2

Reaction notes

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