18-Crown-6 → (E)-tert-butyl 2-(5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1H-indol-1-yl)-2-oxoethylcarbamate

HRID 1503705Notes

Reaction equation

HRID 1503705 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:10]([C:22]([F:25])([F:24])[F:23])/[CH:11]=[CH:12]/[C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[NH:18][CH:17]=[CH:16]3)[CH:5]=[C:6]([Cl:9])[C:7]=1[F:8].[C:26]([O:30][C:31]([NH:33][CH2:34][C:35](OC1C=CC([N+]([O-])=O)=CC=1)=[O:36])=[O:32])([CH3:29])([CH3:28])[CH3:27].[F-].[K+].C1OCCOCCOCCOCCOCCOC1.CCN(C(C)C)C(C)C>C(#N)C.C(Cl)Cl>[Cl:9][C:6]1[CH:5]=[C:4]([CH:10]([C:22]([F:24])([F:23])[F:25])/[CH:11]=[CH:12]/[C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[N:18]([C:35](=[O:36])[CH2:34][NH:33][C:31](=[O:32])[O:30][C:26]([CH3:27])([CH3:28])[CH3:29])[CH:17]=[CH:16]3)[CH:3]=[C:2]([Cl:1])[C:7]=1[F:8]

Participants

8

Reactant 5

HCID 2855718-Crown-6HCID 77217Boc-Gly-ONpHCID 81531DiisopropylethylamineHCID 522689Potassium FluorideHCID 86675169(E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1H-indole

Product 1

HCID 86675171(E)-tert-butyl 2-(5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1H-indol-1-yl)-2-oxoethylcarbamate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1H-indole (0.1 g, 0.258 mmol) in acetonitrile (5.0 mL) was added 4-nitrophenyl 2-(tert-butoxycarbonylamino)acetate (0.114 g, 0.387 mmol), potassium fluoride (0.03 g, 0.516 mmol), 18-crown-6-ether (0.075 g, 0.283 mmol) and DIEA (0.0332 g, 0.258 mmol) and the reaction was stirred at RT for 16 h. The reaction mixture was concentrated to obtain a residue which was diluted with DCM and washed with water and brine solution. The separated DCM layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford the crude title compound as a light brown gummy material which was used in the next step without further purification (0.1 g): ESIMS m/z 545.23 ([M+H]+).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customto obtain a residue which
  3. washwashed with water and brine solution
  4. dry with materialThe separated DCM layer was dried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-368eb2b852674a5ea7ff0d120ce86ef6
Source dataset
uspto-grants-2015_12
Patent number
US09212164B2

Reaction notes

Loading…