Trifluoroacetic acid → Ethyl 4-{3-[1-benzhydryl-5-chloro-2-(2-{[(3,4-dichlorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoate

HRID 2181492Notes

Reaction equation

HRID 2181492 reaction equation
[CH:1]([N:14]1[C:22]2[C:17](=[CH:18][C:19]([Cl:23])=[CH:20][CH:21]=2)[CH:16]=[C:15]1[CH2:24][CH2:25][NH:26][S:27]([CH2:30][C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[C:33]([Cl:38])[CH:32]=1)(=[O:29])=[O:28])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([SiH](CC)CC)C.[CH2:46]([O:48][C:49](=[O:60])[C:50]1[CH:55]=[CH:54][C:53]([CH2:56][CH2:57][CH:58]=O)=[CH:52][CH:51]=1)[CH3:47].FC(F)(F)C(O)=O.C([O-])(O)=O.[Na+]>ClCCl>[CH:1]([N:14]1[C:22]2[C:17](=[CH:18][C:19]([Cl:23])=[CH:20][CH:21]=2)[C:16]([CH2:58][CH2:57][CH2:56][C:53]2[CH:54]=[CH:55][C:50]([C:49]([O:48][CH2:46][CH3:47])=[O:60])=[CH:51][CH:52]=2)=[C:15]1[CH2:24][CH2:25][NH:26][S:27]([CH2:30][C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[C:33]([Cl:38])[CH:32]=1)(=[O:28])=[O:29])([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 516892Sodium BicarbonateHCID 2757377Ethyl 4-(3-oxopropyl)benzoateHCID 11204051N-[2-(1-benzhydryl-5-chloro-1H-indol-2-yl)ethyl]-1-(3,4-dichlorophenyl)methanesulfonamide

Product 1

HCID 11239705Ethyl 4-{3-[1-benzhydryl-5-chloro-2-(2-{[(3,4-dichlorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoateYield 56.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-10 °C

Procedure

To a solution N-[2-(1-benzhydryl-5-chloro-1H-indol-2-yl)ethyl]-1-(3,4-dichlorophenyl)-methanesulfonamide (3.0 g, 5.14 mmol), triethylsilane (1.79 g, 15.4 mmol), and 4-(3-oxopropyl)benzoic acid ethyl ester (1.26 g, 6.16 mmol) in dichloromethane (30 mL) at −20 to −25° C. was added trifloroacetic acid (2.93 g, 25.7 mmol) during a period of 1 min. The mixture was warmed to −10° C. and stirred for 4 h. Saturated aqueous NaHCO3 (20 mL) was added. The mixture was extracted with EtOAc (150 mL). The organic extract was dried over Na2SO4. The solvent is evaporated. The residue is purified by column chromatography, using a mixture of heptane and EtOAc (4:1) as elute to give a white solid (2.25 g, 56%). 1H NMR (CDCl3): δ6.9-7.6 (m, Ph, CHPh2), 7.97 (d, 1H, J=1.6 Hz), 7.41 (d, 1H, J=1.9 Hz), 6.50 (d, 1H, J=8.9 Hz), 4.35 (dd, 2H, J=7.1, 14.3 Hz), 4.13 (m, 1H), 3.92 (s, 2H), 2.95 (m, 2H), 2.71 (m, 6H), 1.96 (m, 2H), 1.38 (t, 3H, J=7.1 Hz).

Workup

  1. extractionThe mixture was extracted with EtOAc (150 mL)
  2. extractionThe organic extract
  3. dry with materialwas dried over Na2SO4
  4. customThe solvent is evaporated
  5. customThe residue is purified by column chromatography
  6. additiona mixture of heptane and EtOAc (4:1)
  7. washas elute

Sources & evidence

ORD record
ord-0e5fa3af0a094916b94b536be6a48861
Source dataset
uspto-grants-2005_05
Patent number
US06891065B2

Reaction notes

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