8-Bromo-1-ethyl-7-fluoro-1,3,4,9-tetrahydro-pyrano[3,4-b]indole-1-acetic acid, methyl ester → 8-Allyl-1-ethyl-7-fluoro-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid methyl ester

HRID 477170Notes

Reaction equation

HRID 477170 reaction equation
[CH2:1]([CH:5]([Sn])C=C(CCCC)CCCC)[CH2:2]CC.Br[C:18]1[C:19]([F:38])=[CH:20][CH:21]=[C:22]2[C:26]=1[NH:25][C:24]1[C:27]([CH2:36][CH3:37])([CH2:31][C:32]([O:34][CH3:35])=[O:33])[O:28][CH2:29][CH2:30][C:23]2=1>C1C=CC=CC=1.[Pd].CCOCC.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:36]([C:27]1([CH2:31][C:32]([O:34][CH3:35])=[O:33])[C:24]2[NH:25][C:26]3[C:22]([C:23]=2[CH2:30][CH2:29][O:28]1)=[CH:21][CH:20]=[C:19]([F:38])[C:18]=3[CH2:5][CH:1]=[CH2:2])[CH3:37]

Participants

7

Reactant 2

HCID 147700098-Bromo-1-ethyl-7-fluoro-1,3,4,9-tetrahydro-pyrano[3,4-b]indole-1-acetic acid, methyl esterHCID 86589045Tributylallyltin

Product 1

HCID 147700108-Allyl-1-ethyl-7-fluoro-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid methyl esterYield 78%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 241BenzeneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
80 °C

Procedure

According to the procedure of Kosugi et al, Chem. Letters 301 (1977) tetrakis-(triphenylphosphine) palladium [O] (60 mg) was added to a mixture of tributylallyltin (1.75 g, 0.0053 mol) and 8-bromo-1-ethyl-7-fluoro-1,3,4,9-tetrahydro-pyrano[3,4-b]indole-1-acetic acid, methyl ester (1.6 g, 0.0043 mol) in benzene (4.0 mL) under N2. The sealed tube was then heated to 80° C. for 15 hours, more palladium catalyst was added (30 mg), and heating continued for 42 hours at 110°-120° C. The cooled reaction mixture was diluted with Et2O, then filtered through a glass wool plug. The ether was washed twice with brine, then dried (MgSO4) to yield an oil that was purified via flash chromatography. Using 1:7 EtOAc:hexane to afford 1.12 g, (~78%) of 1-ethyl-7-fluoro-1,3,4,9-tetrahydro-8-(2-propenyl)-pyrano[3,4-b]indole-1-acetic acid, methyl ester as a colorless oil. The oil was dissolved in ethanol (40 mL) and 1N sodium hydroxide added (15 mL). The mixture was heated to reflux for 2 hours then cooled and concentrated. 1N HCl was added and the aqueous solution extracted with ether. The ether layers were washed (brine), dried (MgSO4) and concentrated to yield a foamy oil. This was purified by flash chromatography on SiO2 -pretreated with 2% H3PO4 -MeOH. Using 1:2 EtOAc:hexane to give 1 g (73%) of 1-ethyl-7-fluoro-1,3,4,9-tetrahydro-8-(2-propenyl)-pyrano[3,4-b]indole-1-acetic acid as a colorless oil which crystallized from toluene:petroleum ether, m.p. 123°-125° C.

Workup

  1. temperatureheating
  2. customThe cooled reaction mixture
  3. filtrationfiltered through a glass wool plug
  4. washThe ether was washed twice with brine
  5. dry with materialdried (MgSO4)
  6. customto yield an oil that
  7. customwas purified via flash chromatography

Sources & evidence

ORD record
ord-49760c36eb8e449ebe9826fc2760e502
Source dataset
uspto-grants-1989_12
Patent number
US04886886

Reaction notes

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