Ethyl Acetate → HCID 19937311, compound

HRID 1672138Notes

Reaction equation

HRID 1672138 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][C:13]([F:18])([F:17])[C:14](O)=[O:15].C(OCC)(=O)C>C1COCC1.O>[F:18][C:13]([F:17])([CH2:14][OH:15])[CH2:12][N:3]1[C:2](=[O:1])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]1=[O:11]

Participants

5

Reactant 2

HCID 8857Ethyl AcetateHCID 591583333-(1,3-Dioxo-2,3-dihydro-1H-isoindol-2-yl)-2,2-difluoropropanoic acid

Product 1

HCID 19937311HCID 19937311, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Under argon atmosphere 3-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-2,2-difluoro-propionic acid, A2 (13.74 g, 53.85 mmol), dissolved in THF (200 mL) was treated with borane-methylsulfide complex (6.3 mL, 5.04 g, 66.6 mmol). After stirring overnight an additional portion of borane-methylsulfide complex (6.0 mL, 4.80 g, 63.43 mmol) was added. When the reaction was complete it was cautiously diluted with water and extracted with ethyl acetate (2×). An ethyl acetate solution prepared from the residue obtained by evaporation of the initial ethyl acetate extractions at 30° C. in vacuo was washed with water, brine (2×), dried (Na2SO4), filtered, and evaporated in vacuo at 30° C. Crude A3 was sonicated in ethyl acetate, and filtered to give pure 2-(2,2-Difluoro-3-hydroxy-propyl)-isoindole-1,3-dione, A3 (7.45 g). Flash chromatography of the liquor residue (Yamazen, 5 L silica gel cartridge, ethyl acetate/hexane gradient) afforded additional pure 2-(2,2-Difluoro-3-hydroxy-propyl)-isoindole-1,3-dione, A3 (1.39 g).

Workup

  1. additionwas treated with borane-methylsulfide complex (6.3 mL, 5.04 g, 66.6 mmol)
  2. additionwas added
  3. extractionextracted with ethyl acetate (2×)
  4. customAn ethyl acetate solution prepared from the residue
  5. washwas washed with water, brine (2×)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated in vacuo at 30° C
  9. customCrude A3 was sonicated in ethyl acetate
  10. filtrationfiltered

Sources & evidence

ORD record
ord-6d94f156827b4e99ac64a4e6e303493b
Source dataset
uspto-grants-2011_08
Patent number
US07998950B2

Reaction notes

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