Trifluoroacetic acid → Ethyl {4-[4,9-bis(ethyloxy)-1-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl]-2-fluorophenyl}acetate

HRID 889502Notes

Reaction equation

FC(F)(F)C(O)=O.[CH2:8]([O:10][C:11]1[C:19]2[C:18](=O)[N:17]([C:21]3[CH:26]=[CH:25][C:24]([CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])=[C:23]([F:33])[CH:22]=3)[CH:16]([OH:34])[C:15]=2[C:14]([O:35][CH2:36][CH3:37])=[C:13]2[CH:38]=[CH:39][CH:40]=[CH:41][C:12]=12)[CH3:9].C([SiH](CC)CC)C>ClCCl>[CH2:8]([O:10][C:11]1[C:19]2[CH2:18][N:17]([C:21]3[CH:26]=[CH:25][C:24]([CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])=[C:23]([F:33])[CH:22]=3)[C:16](=[O:34])[C:15]=2[C:14]([O:35][CH2:36][CH3:37])=[C:13]2[CH:38]=[CH:39][CH:40]=[CH:41][C:12]=12)[CH3:9]

Participants

Conditions

Temperature: 0 °C

Procedure

Trifluoroacetic acid (1900 mL) was added to a stirred solution of ethyl {4-[4,9-bis(ethyloxy)-1-hydroxy-3-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl]-2-fluorophenyl}acetate (898 g, 1.92 mol) in dichloromethane (1900 mL) at 0° C. under a nitrogen atmosphere. Triethylsilane (465 mL, 2.92 mol) was added dropwise to the deep red solution ensuring that the temperature was maintained below 3° C. The reaction mixture was then stirred at 0° C. for 45 minutes, over which time the solution turned yellow and all ethyl {-4-[4,9-bis(ethyloxy)-1-hydroxy-3-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl]-2-fluorophenyl}acetate was shown to be consumed by TLC analysis (silica, dichloromethane:methanol, 99:1). The reaction mixture was evaporated to dryness under reduced pressure, slurried in hexane (2×2.5 L) and then isopropanol (2.5 L) at 40° C. and dried under vacuum to give the desired product as a white solid (821 g, 95% yield).

Workup

temperaturewas maintained below 3° C
customto be consumed by TLC analysis (silica, dichloromethane:methanol, 99:1)
customThe reaction mixture was evaporated to dryness under reduced pressure
dry with materialisopropanol (2.5 L) at 40° C. and dried under vacuum

Sources & evidence

ORD record: ord-d4b3d67fa25543a886e38b4e80e52e1a
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08252833B2

Reaction notes

Loading…