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

HRID 889490Notes

Reaction equation

HRID 889490 reaction equation
[CH2:1]([O:3][C:4]1[C:12]2[C:11](=[O:13])[N:10]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])=[C:16]([F:26])[CH:15]=3)[C:9](=[O:27])[C:8]=2[C:7]([O:28][CH2:29][CH3:30])=[C:6]2[CH:31]=[CH:32][CH:33]=[CH:34][C:5]=12)[CH3:2].O1CCCC1.[BH4-].[Na+]>CO>[CH2:29]([O:28][C:7]1[C:8]2[C:9](=[O:27])[N:10]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])=[C:16]([F:26])[CH:15]=3)[CH:11]([OH:13])[C:12]=2[C:4]([O:3][CH2:1][CH3:2])=[C:5]2[CH:34]=[CH:33][CH:32]=[CH:31][C:6]=12)[CH3:30]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 4311764Sodium borohydride2×HCID 58399553Ethyl {4-[4,9-bis(ethyloxy)-1,3-dioxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl]-2-fluorophenyl}acetate

Product 1

HCID 58399566Ethyl {4-[4,9-bis(ethyloxy)-1-hydroxy-3-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl]-2-fluorophenyl}acetateYield 107.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Ethyl {4-[4,9-bis(ethyloxy)-1,3-dioxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl]-2-fluorophenyl}acetate (24 g, 51.6 mmol) was suspended in methanol (75 ml) and tetrahydrofuran (200 ml) and cooled to 5° C. in an ice bath. Some solid did not go into solution. Sodium borohydride (2 g, 51.6 mmol) was added portionwise over 2 minutes (effervescence). Undissolved solid slowly went into solution and the colour lightened from dark brown to light brown. LC/MS after 5 minutes and 30 minutes indicated that the reaction had not proceeded to completion. Therefore, after 30 minutes, more sodium borohydride (1 g, 26.3 mmol) was added in one portion (effervescence). LC/MS after a further 30 minutes showed no starting material remaining. The mixture was concentrated in vacuo to give a brown oil that was partitioned between ethyl acetate (300 ml) and water (500 ml). The aqueous layer was further extracted with ethyl acetate (2×100 ml). Combined organics were washed with brine, dried over magnesium sulphate and concentrated to give the title compound as a brown solid (26 g).

Workup

  1. custom30 minutes
  2. waitTherefore, after 30 minutes
  3. waitLC/MS after a further 30 minutes showed
  4. concentrationThe mixture was concentrated in vacuo
  5. customto give a brown oil that
  6. customwas partitioned between ethyl acetate (300 ml) and water (500 ml)
  7. extractionThe aqueous layer was further extracted with ethyl acetate (2×100 ml)
  8. washCombined organics were washed with brine
  9. dry with materialdried over magnesium sulphate
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-b39e407f6edb4bad859db4b2fe70ede1
Source dataset
uspto-grants-2012_08
Patent number
US08252833B2

Reaction notes

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