Nitrogen → 7-(acetylamino)-9a-butyl-4-(1-ethoxyvinyl)-6-fluoro-1,2,9,9a-tetrahydro-3H-fluoren-3-one

HRID 1372521Notes

Reaction equation

HRID 1372521 reaction equation
[C:1]([NH:4][C:5]1[CH:17]=[C:16]2[C:8]([C:9]3[C:14]([CH2:18][CH2:19][CH2:20][CH3:21])([CH2:15]2)[CH2:13][CH2:12][C:11](=[O:22])[C:10]=3Br)=[CH:7][C:6]=1[F:24])(=[O:3])[CH3:2].N#N.C([Sn](CCCC)(CCCC)[C:32]([O:34][CH2:35][CH3:36])=[CH2:33])CCC>C1(C)C=CC=CC=1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]([NH:4][C:5]1[CH:17]=[C:16]2[C:8]([C:9]3[C:14]([CH2:18][CH2:19][CH2:20][CH3:21])([CH2:15]2)[CH2:13][CH2:12][C:11](=[O:22])[C:10]=3[C:32]([O:34][CH2:35][CH3:36])=[CH2:33])=[CH:7][C:6]=1[F:24])(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 947NitrogenHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 179727237-(acetylamino)-4-bromo-9a-butyl-6-fluoro-1,2,9,9a-tetrahydro-3H-fluoren-3-one

Product 1

HCID 179727157-(acetylamino)-9a-butyl-4-(1-ethoxyvinyl)-6-fluoro-1,2,9,9a-tetrahydro-3H-fluoren-3-oneYield 49%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A partial solution of 7-(acetylamino)-4-bromo-9a-butyl-6-fluoro-1,2,9,9a-tetrahydro-3H-fluoren-3-one (495 mg, 1.26 mmol) in anhydrous toluene (6.3 mL) was purged with N2, treated with dichlorobis(triphenylphosphine)palladium(II) (177 mg, 0.25 mmol), purged with N2, and treated with tributyl(1-ethoxyvinyl)tin (0.600 mL, 1.9 mmol). The resulting mixture was stirred under a N2 atmosphere and heated in an oil bath at 100° C. for two hours. After cooling to room temperature, the mixture was filtered through a pad of silica gel, washing the product off with EtOAc. The filtrate and washings were evaporated under vacuum to an oil. The crude product was purified by flash chromatography on a Biotage 40S KP-Sil column, eluting with 4:1 hexanes-EtOAc (1 L) followed by 2:1 hexanes-EtOAc (1 L). The product containing fractions were concentrated under vacuum to afford 7-(acetylamino)-9a-butyl-4-(1-ethoxyvinyl)-6-fluoro-1,2,9,9a-tetrahydro-3H-fluoren-3-one (238 mg, 49%) as a yellow foam.

Workup

  1. custompurged with N2
  2. temperatureAfter cooling to room temperature
  3. filtrationthe mixture was filtered through a pad of silica gel
  4. washwashing the product off with EtOAc
  5. customThe filtrate and washings were evaporated under vacuum to an oil
  6. customThe crude product was purified by flash chromatography on a Biotage 40S KP-Sil column
  7. washeluting with 4:1 hexanes-EtOAc (1 L)
  8. additionThe product containing fractions
  9. concentrationwere concentrated under vacuum

Sources & evidence

ORD record
ord-86bcc47aedd147f38fd475c1198c0d61
Source dataset
uspto-grants-2007_01
Patent number
US07157604B2

Reaction notes

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