Cesium carbonate → Tert-butyl 2-phenylsulfonyl-4,5-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole-carboxylate

HRID 2036731Notes

Reaction equation

HRID 2036731 reaction equation
Br[C:2]1[CH:10]=[C:9]([CH3:11])[C:8]2[N:7]([CH3:12])[C:6]3[CH2:13][CH:14]4[NH:18][CH:17]([C:5]=3[C:4]=2[C:3]=1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:16][CH2:15]4.[C:26]1([S:32]([O-:34])=[O:33])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[Na+].C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[C:26]1([S:32]([C:2]2[CH:10]=[C:9]([CH3:11])[C:8]3[N:7]([CH3:12])[C:6]4[CH2:13][CH:14]5[NH:18][CH:17]([C:5]=4[C:4]=3[C:3]=2[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:16][CH2:15]5)(=[O:34])=[O:33])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 2723840Benzenesulfinic acid, sodium saltHCID 67085249Tert-butyl 2-bromo-4,5-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole-carboxylate

Product 1

HCID 67085505Tert-butyl 2-phenylsulfonyl-4,5-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole-carboxylateYield 41.4%

Reagents, catalysts & solvents 2

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 1140TolueneSolvent

Procedure

A mixture of the product of step C (230 mg, 0.57 mmol), sodium benzenesulfinate (112 mg, 0.68 mmol), di-palladium-tris(dibenzylideneacetone) (52 mg, 0.057 mmol), cesium carbonate (277 mg, 0.85 mmol), xantphos (66 mg, 0.11 mmol) and tetrabutyl ammonium chloride (189 mg, 0.68 mmol) was taken up in toluene (3.2 mL). The reaction flask was purged with nitrogen and heated at reflux for 4 h under a nitrogen atmosphere. After cooling to ambient temperature the reaction mixture was filtered through a celite pad and the resulting filtrate concentrated in vacuo. The crude product was purified by flash column chromatography (SiO2, 7.5:2.5 hexanes/ethyl acetate) to give tert-butyl 2-phenylsulfonyl-4,5-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole-carboxylate (110 mg, 41%) as an off-white solid: 1H NMR (CDCl3, 300 MHz): δ 8.02 (br s, 1H), 7.93-7.96 (m, 2H), 7.40-7.52 (m, 3H), 7.34 (br s, 1H), 5.13-5.33 (m, 1H), 4.53-4.80 (m, 1H), 3.83 (s, 3H), 3.14-3.47 (m, 1H), 2.74 (s, 3H), 2.45 (d, J=15.9 Hz, 1H), 2.10-2.38 (m, 2H), 1.86-1.98 (m, 1H), 1.58-1.67 (m, 1H), 1.37 (br s, 9H).

Workup

  1. customThe reaction flask was purged with nitrogen
  2. temperatureheated
  3. temperatureat reflux for 4 h under a nitrogen atmosphere
  4. filtrationwas filtered through a celite pad
  5. concentrationthe resulting filtrate concentrated in vacuo
  6. customThe crude product was purified by flash column chromatography (SiO2, 7.5:2.5 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-604bde5ec36b4144895924dbaa62564a
Source dataset
uspto-grants-2013_11
Patent number
US08575186B2

Reaction notes

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