Ethyl Acetate → ethyl 3-(6-fluoro-5-nitro-1H-indol-2-yl)-3-methylbutanoate

HRID 1964465Notes

Reaction equation

HRID 1964465 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][C:3]=1[C:12]#[C:13][C:14]([CH3:22])([CH3:21])[CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17].C(OCC)(=O)C>CC#N.Cl[Pd]Cl>[F:8][C:6]1[CH:7]=[C:2]2[C:3]([CH:12]=[C:13]([C:14]([CH3:21])([CH3:22])[CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[NH:1]2)=[CH:4][C:5]=1[N+:9]([O-:11])=[O:10]

Participants

5

Reactant 2

HCID 8857Ethyl AcetateHCID 59129516Ethyl 5-(2-amino-4-fluoro-5-nitrophenyl)-3,3-dimethylpent-4-ynoate

Product 1

HCID 59129505ethyl 3-(6-fluoro-5-nitro-1H-indol-2-yl)-3-methylbutanoateYield 100.3%

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 6342AcetonitrileSolvent

Procedure

To a mixture of ethyl 5-(2-amino-4-fluoro-5-nitrophenyl)-3,3-dimethylpent-4-ynoate (34.5 g, 0.11 mol) and PdCl2(10.4 g, 58.6 nmol) in CH3CN (350 mL) was heated to reflux for 1.5 hours. The reaction mixture was cooled down to room temperature. Ethyl acetate (300 mL) was added, the precipitate was filtered off and washed with methanol. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate 40:1) to give ethyl 3-(6-fluoro-5-nitro-1H-indol-2-yl)-3-methylbutanoate (34.0 g, 98%) as a deep yellow solid. 1H NMR (300 MHz, CDCl3) δ 10.11 (brs, 1 H), 8.30 (d, J=7.2 Hz, 1 H), 7.14 (d, J=11.7 Hz, 1 H), 6.35 (d, J=1.5 Hz, 1 H), 4.17 (q, J=7.2 Hz, 2 H), 2.69 (s, 2 H), 1.51 (s, 6 H), 1.25 (t, J=7.2 Hz, 3 H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 1.5 hours
  3. filtrationthe precipitate was filtered off
  4. washwashed with methanol
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate 40:1)

Sources & evidence

ORD record
ord-d62dc80428934a40af7eadecc2e21ce7
Source dataset
uspto-grants-2013_04
Patent number
US08415387B2

Reaction notes

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