Triphenylphosphine → 5-Ethoxycarbonylmethylene-7-fluoro-1-oxo-1,3,4,5-tetrahydro-azepino[3,4-b]indole-2,10-dicarboxylic acid di-tert-butyl ester

HRID 2234771Notes

Reaction equation

HRID 2234771 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20]([O:24][C:25]([N:27]1[C:35]2[C:30](=[CH:31][C:32]([F:36])=[CH:33][CH:34]=2)[C:29](I)=[C:28]1[C:38]([N:40]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:41][CH2:42][CH:43]=[CH:44][C:45]([O:47][CH2:48][CH3:49])=[O:46])=[O:39])=[O:26])([CH3:23])([CH3:22])[CH3:21]>C1COCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:53]([O:52][C:50]([N:40]1[CH2:41][CH2:42][C:43](=[CH:44][C:45]([O:47][CH2:48][CH3:49])=[O:46])[C:29]2[C:30]3[C:35](=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=3)[N:27]([C:25]([O:24][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:26])[C:28]=2[C:38]1=[O:39])=[O:51])([CH3:55])([CH3:56])[CH3:54]

Participants

5

Reactant 2

HCID 11776TriphenylphosphineHCID 686374172-[Tert-butoxycarbonyl-(4-ethoxycarbonyl-but-3-enyl)-aminocarbonyl]-5-fluoro-3-iodo-indole-1-carboxylic acid tert-butyl ester

Product 1

HCID 686390865-Ethoxycarbonylmethylene-7-fluoro-1-oxo-1,3,4,5-tetrahydro-azepino[3,4-b]indole-2,10-dicarboxylic acid di-tert-butyl ester

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of triphenylphosphine (3.36 g, 12.8 mmol), Pd(OAc)2 (1.44 g, 6.40 mmol) and Ag2CO3 (3.53 g, 12.8 mmol) in anhydrous THF (100 mL) is stirred at room temperature for 15 minutes. A solution of 2-[tert-butoxycarbonyl-(4-ethoxycarbonyl-but-3-enyl)-aminocarbonyl]-5-fluoro-3-iodo-indole-1-carboxylic acid tert-butyl ester (4.03 g, 6.40 mmol), prepared as in reference 15, in THF (10 mL) is added to the above prepared suspension. The mixture is heated at 60° C. for 16 hours. The inorganic precipitate is removed and the organic layer is concentrated. The residue is purified by silica gel column chromatography and eluted with EtOAc-Hexanes to give the 5-ethoxycarbonylmethylene-7-fluoro-1-oxo-1,3,4,5-tetrahydro-azepino[3,4-b]indole-2,10-dicarboxylic acid di-tert-butyl ester; 1H NMR (CDCl3) δ 1.34 (t, 3H, J=7.6 Hz), 1.57 (s, 9H), 1.60 (s, 9H), 3.46-3.52 (m, 2H), 4.13 (t, 2H, J=4.8 Hz), 4.24 (q, 2H, J=7.6 Hz), 6.30 (t, 1H, J=2.8 Hz), 7.21 (td, 1H, J1=2.8 Hz, J2=9.2 Hz), 7.42 (dd, 1H, J1=2.8 Hz, J2=8.8 Hz), 8.10 (dd, 1H, J1=4.0 Hz, J2=9.2 Hz); m/z [M++Na] 525.0.

Workup

  1. temperatureThe mixture is heated at 60° C. for 16 hours
  2. customThe inorganic precipitate is removed
  3. concentrationthe organic layer is concentrated
  4. customThe residue is purified by silica gel column chromatography
  5. washeluted with EtOAc-Hexanes

Sources & evidence

ORD record
ord-62519ecf8a9e474398757aeb120112dd
Source dataset
uspto-grants-2010_05
Patent number
US07713958B2

Reaction notes

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