Trifluoroacetic acid → HCID 68089489, compound

HRID 1918228Notes

Reaction equation

HRID 1918228 reaction equation
[CH2:1]([N:8]1[CH2:12][C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=2)[C@:10]([NH:21][C:22](=O)OC(C)(C)C)([CH3:20])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].S(OC)(OC)(=O)=O.C(O)(C(F)(F)F)=O.CCN(C(C)C)C(C)C.Cl[C:59]([O:61][C:62]1[CH:67]=[CH:66][C:65]([F:68])=[CH:64][CH:63]=1)=[O:60]>CS(C)=O>[F:68][C:65]1[CH:66]=[CH:67][C:62]([O:61][C:59](=[O:60])[N:21]([C@:10]2([CH3:20])[C@@H:11]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=3)[CH2:12][N:8]([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH2:9]2)[CH3:22])=[CH:63][CH:64]=1

Participants

8

Reactant 6

HCID 6422Trifluoroacetic acidHCID 6497Dimethyl SulfateHCID 81531DiisopropylethylamineHCID 27332564-Fluorophenyl chloroformateHCID 23665647Potassium tert-butoxideHCID 68089406HCID 68089406, compound

Product 1

HCID 68089489HCID 68089489, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A mixture of 2.49 g (6.21 mmol) rac-tert-butyl (3R,4S)-1-benzyl-4-(4-chlorophenyl)-3-methylpyrrolidin-3-ylcarbamate, 0.836 g (7.45 mmol) potassium tert.-butoxide and 0.98 g (7.76 mmol) dimethyl sulfate in 80 mL DMSO was stirred at room temperature for 1 h. The mixture was poured onto ice-water and extracted with TBME. The combined organic layers were washed with brine, died with Na2SO4, filtered off and evaporated to dryness. The residue was dissolved in 40 mL DCM and 7.68 g (67.3 mmol) TFA was added. The mixture was stirred at room temperature over night and ice-water was added. The pH was adjusted to 12 and the organic layer was washed with brine. The aqueous layer was extracted with DCM and the combined organic layers were dried with Na2SO4, filtered off and evaporated to dryness. The residue was dissolved in 40 mL DCM and 1.04 g (8.08 mmol) DIPEA and at −15° C. 1.29 g (7.41 mmol) 4-fluorophenyl chloroformate was added. The mixture was stirred to 0° C. during 2 h and concentrated under vacuum the residue was purified by column chromatography on silica eluting with a gradient formed from heptane and ethyl acetate to yield after evaporation of the product containing fractions 1.68 g (59%) of the title compound as light brown viscous oil. MS m/e: 453.1 [M+H]+.

Workup

  1. additionThe mixture was poured onto ice-water
  2. extractionextracted with TBME
  3. washThe combined organic layers were washed with brine
  4. filtrationfiltered off
  5. customevaporated to dryness
  6. dissolutionThe residue was dissolved in 40 mL DCM
  7. stirringThe mixture was stirred at room temperature over night
  8. washthe organic layer was washed with brine
  9. extractionThe aqueous layer was extracted with DCM
  10. dry with materialthe combined organic layers were dried with Na2SO4
  11. filtrationfiltered off
  12. customevaporated to dryness
  13. dissolutionThe residue was dissolved in 40 mL DCM
  14. customat −15° C
  15. stirringThe mixture was stirred to 0° C. during 2 h
  16. concentrationconcentrated under vacuum the residue
  17. customwas purified by column chromatography on silica eluting with a gradient
  18. customformed from heptane and ethyl acetate
  19. customto yield
  20. customafter evaporation of the product
  21. additioncontaining fractions 1.68 g (59%) of the title compound as light brown viscous oil

Sources & evidence

ORD record
ord-528f78c496904127883ef65ddc91f3c9
Source dataset
uspto-grants-2013_12
Patent number
US08618303B2

Reaction notes

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