Tetrahydrofuran → HCID 67374271, compound

HRID 1677078Notes

Reaction equation

HRID 1677078 reaction equation
C[Mg]Br.O1CCC[CH2:5]1.CCOC([C@H:14]1[CH2:18][CH2:17][C@@H:16]([C:19]2[CH:24]=[C:23]([F:25])[C:22]([F:26])=[C:21]([F:27])[CH:20]=2)[N:15]1C(OC(C)(C)C)=O)=O.[Cl-].[NH4+].C([O:40][CH2:41][CH3:42])(=O)C>>[F:25][C:23]1[CH:24]=[C:19]([C@H:16]2[NH:15][C@@H:14]([C:41]([OH:40])([CH3:42])[CH3:5])[CH2:18][CH2:17]2)[CH:20]=[C:21]([F:27])[C:22]=1[F:26]

Participants

6

Reactant 5

HCID 8028TetrahydrofuranHCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 67374560HCID 67374560, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 67374271HCID 67374271, compound

Procedure

Under a nitrogen atmosphere and under ice-cooling, methyl magnesium bromide (20.7 mL, 0.97M tetrahydrofuran solution) was added dropwise into a tetrahydrofuran (50 mL) solution of (2R,5S)-5-(3,4,5-trifluorophenyl)pyrrolidine-1,2-dicarboxylic acid 1-t-butyl ester 2-ethyl ester (2.5 g). After stirring for 2 hours at the same temperature, ammonium chloride aqueous solution and ethyl acetate were added, and the organic layer was partitioned. The organic layer was washed with brine and was dried with magnesium sulfate, and the solvent was removed under a vacuum. Ethyl acetate (7 mL) and 4 N hydrochloric acid/ethyl acetate (20 mL) were added to the residue, and stirring was continued for 1 hour at room temperature. The solvent was removed under a vacuum, and ethyl acetate and sodium bicarbonate aqueous solution were added, and the organic layer was partitioned. The organic layer was washed with brine and dried over anhydrous magnesium sulfate, and the solvent was removed under a vacuum, and the residue was purified by silica gel column chromatography (heptane/ethyl acetate→ethyl acetate), and the title compound (745 mg) was obtained. The physical property values are as follows.

Workup

  1. temperatureUnder a nitrogen atmosphere and under ice-cooling
  2. additionwere added
  3. customthe organic layer was partitioned
  4. washThe organic layer was washed with brine
  5. dry with materialwas dried with magnesium sulfate
  6. customthe solvent was removed under a vacuum
  7. additionEthyl acetate (7 mL) and 4 N hydrochloric acid/ethyl acetate (20 mL) were added to the residue
  8. customThe solvent was removed under a vacuum, and ethyl acetate and sodium bicarbonate aqueous solution
  9. additionwere added
  10. customthe organic layer was partitioned
  11. washThe organic layer was washed with brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. customthe solvent was removed under a vacuum
  14. customthe residue was purified by silica gel column chromatography (heptane/ethyl acetate→ethyl acetate)

Sources & evidence

ORD record
ord-f16f7520f3a045268ac97bfef3e3e6f5
Source dataset
uspto-grants-2011_08
Patent number
US08008293B2

Reaction notes

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