1-Penten-3-one → 5-Amino-2-butyl-6-fluoro-2-(3-oxopentyl)-1-indanone

HRID 1372512Notes

Reaction equation

[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])C(=O)[CH:6]([CH2:13][CH2:14][CH2:15][CH3:16])[CH2:5]2.[CH3:17][O-:18].[Na+].[CH:20]([C:22]([CH2:24][CH3:25])=[O:23])=[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:17](=[O:18])[C:6]([CH2:13][CH2:14][CH2:15][CH3:16])([CH2:21][CH2:20][C:22](=[O:23])[CH2:24][CH3:25])[CH2:5]2

Participants

Conditions

Temperature: 70 °C

Procedure

A solution of 5-amino-2-butyl-6-fluoro-1-indanone (0.81 g, 3.84 mmol) in ethanol (18 mL) was treated with sodium methoxide (0.5M solution in MeOH, 1.54 mL, 0.768 mmol) and ethyl vinyl ketone (0.572 mL, 5.76 mmol). The resulting solution was stirred under a nitrogen atmosphere and heated in an oil bath at 70° C. over night. After cooling to room temperature, 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 4:1 to 3:1 hexanes-EtOAc. The product containing fractions were evaporated under vacuum to provide to afford 5-amino-2-butyl-6-fluoro-2-(3-oxopentyl)-1-indanone(0.51 g, 45%) as a yellow foam.

Workup

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

Sources & evidence

ORD record: ord-051c2020debf4a59a6bc8f99ce07ccd5
Source dataset: uspto-grants-2007_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07157604B2

Reaction notes

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