Trifluoroacetic acid → N-[3-(1-ethyl-5-fluoro-indan-1-yl)-1H-indol-7-yl]-methanesulfonamide

HRID 13699

Reaction equation

HRID 13699 reaction equation
[CH2:1]([C:3]1(O)[C:11]2[C:6](=[CH:7][C:8]([F:12])=[CH:9][CH:10]=2)[CH2:5][CH2:4]1)[CH3:2].[NH:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][C:21]=2[NH:23][S:24]([CH3:27])(=[O:26])=[O:25])[CH:16]=[CH:15]1.FC(F)(F)C(O)=O>ClCCl>[CH2:1]([C:3]1([C:16]2[C:17]3[C:22](=[C:21]([NH:23][S:24]([CH3:27])(=[O:25])=[O:26])[CH:20]=[CH:19][CH:18]=3)[NH:14][CH:15]=2)[C:11]2[C:6](=[CH:7][C:8]([F:12])=[CH:9][CH:10]=2)[CH2:5][CH2:4]1)[CH3:2]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 20231824n-(1h-Indol-7-yl)methanesulfonamideHCID 593404281-Ethyl-5-fluoroindan-1-ol

Product 1

HCID 11268772N-[3-(1-ethyl-5-fluoro-indan-1-yl)-1H-indol-7-yl]-methanesulfonamideYield 84.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Combine 1-ethyl-5-fluoro-indan-1-ol (502 mg, 2.79 mmol, 1.30 equivalents), N-(1H-Indol-7-yl)-methanesulfonamide (450 mg, 2.14 mmol, 1.00 equivalents), and trifluoroacetic acid (0.25 ml, 3.21 mmol, 1.50 equivalents) in dichloromethane (5 ml) and stir at room temperature under nitrogen overnight. Load the solution on silica and purify eluting with 0 to 100% ethyl acetate/hexanes over 25 minutes to obtain the title compound (672 mg, 84%). LC-MS m/z 373.0 (M++1). The racemic mixture is separated on a Chiralcel OJ 8×33 cm column eluting with methanol with 0.2% dimethylethylamine (flow: 375 ml/min, UV detection at 230 nm) to provide the individual enantiomers, Examples 1A and 1B, in 96.3% ee and 97.4% ee, respectively.

Workup

  1. customLoad the solution on silica and purify
  2. washeluting with 0 to 100% ethyl acetate/hexanes over 25 minutes

Sources & evidence

ORD record
ord-fbe7d318a9d74414884f73b6d827b33f
Source dataset
uspto-grants-2010_06
Patent number
US07728150B2

Linked notes

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