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

HRID 2036680Notes

Reaction equation

HRID 2036680 reaction equation
Br[C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH3:11])[C:6]3[CH2:12][CH:13]4[NH:17][CH:16]([C:5]=3[C:4]=2[C:3]=1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:15][CH2:14]4.[Na+].[C:26]1([S:32]([O-:34])=[O:33])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.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>[C:26]1([S:32]([C:2]2[CH:10]=[CH:9][C:8]3[N:7]([CH3:11])[C:6]4[CH2:12][CH:13]5[NH:17][CH:16]([C:5]=4[C:4]=3[C:3]=2[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:15][CH2:14]5)(=[O:34])=[O:33])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 2723840Benzenesulfinic acid, sodium saltHCID 67085938Tert-butyl 2-bromo-5-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole-carboxylate

Product 1

HCID 67085547Tert-butyl 2-phenylsulfonyl-5-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole-carboxylateYield 71%

Reagents, catalysts & solvents 3

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 1140TolueneSolvent

Procedure

A mixture of product from step B (1.5 g, 3.84 mmol) and benzene sulfinic acid sodium salt (755 mg, 4.6 mmol) were suspended in toluene (30 mL) and N2 was bubbled through the reaction mixture for 10-15 min. Di-palladium-tris(dibenzylideneacetone) (89 mg, 0.096 mmol), cesium carbonate (1.84 g, 5.76 mmol), xantphos (111 mg, 0.192 mmol) and tetrabutylammonium chloride (1.28 g, 4.6 mmol) were then added sequentially, and the reaction was heated to reflux for 12 h. The reaction mixture was cooled to ambient temperature, partitioned between ethyl acetate and sat. ammonium chloride solution and the organics removed. The aqueous was extracted with ethyl acetate (×2) and the combined organics dried over sodium sulfate and concentrated. Purification by flash column chromatography (silica gel, hexanes/EtOAc, 100:0 to 50:50) provided tert-butyl 2-phenylsulfonyl-5-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole-carboxylate (1.22 g, 71%) as a yellow solid: 1H NMR (300 MHz, CDCl3) δ 8.20 (s, 1H), 7.96 (dd, J=7.7, 1.5 Hz, 2H), 7.68 (d, J=9.0 Hz, 1H), 7.47 (m, 3H), 7.30 (d, J=8.7 Hz, 1H), 5.25 (brs, 1H), 4.68 (m, 1H), 3.60 (s, 3H), 3.37 (m, 1H), 2.50 (d, J=16.7 Hz, 1H), 2.26 (m, 2H), 1.94 (t, J=10.3 Hz, 1H), 1.61 (m, 1H, partially masked by H2O peak), 1.36 (s, 9H).

Workup

  1. customN2 was bubbled through the reaction mixture for 10-15 min
  2. temperaturethe reaction was heated
  3. temperatureto reflux for 12 h
  4. custompartitioned between ethyl acetate and sat. ammonium chloride solution
  5. extractionThe aqueous was extracted with ethyl acetate (×2)
  6. dry with materialthe combined organics dried over sodium sulfate
  7. concentrationconcentrated
  8. customPurification by flash column chromatography (silica gel, hexanes/EtOAc, 100:0 to 50:50)

Sources & evidence

ORD record
ord-3a56840b06ac4b5d9960e261588f7be1
Source dataset
uspto-grants-2013_11
Patent number
US08575186B2

Reaction notes

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