Trifluoroacetic acid → HCID 68089352, compound

HRID 1918234Notes

Reaction equation

HRID 1918234 reaction equation
C(O[C:6](=O)[NH:7][C@H:8]1[C@@:12]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)([CH3:13])[CH2:11][N:10]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:9]1)(C)(C)C.CC(C)([O-])C.[K+].S(OC)(OC)(=O)=O.[OH-].[Na+].C(O)(C(F)(F)F)=O>CS(C)=O>[CH2:21]([N:10]1[CH2:11][C@:12]([C:14]2[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=2)([CH3:13])[C@H:8]([NH:7][CH3:6])[CH2:9]1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 6497Dimethyl SulfateHCID 14798Sodium Hydroxide2×HCID 23665647Potassium tert-butoxideHCID 68089163HCID 68089163, compound

Product 1

HCID 68089352HCID 68089352, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A mixture of 2 g (4.99 mmol) rac-[(3S,4R)-1-Benzyl-4-(4-chloro-phenyl)-4-methyl-pyrrolidin-3-yl]-carbamic acid tert-butyl ester, 0.67 g (5.99 mmol) potassium tert.-butoxide and 0.786 (6.24 mmol) dimethyl sulfate in 40 mL DMSO was stirred for 1 h at room temperature. The mixture was poured on ice-water containing NaOH (1N) and extracted with TBME. The combined organic layers were washed with brine, dried with Na2SO4, filtered and evaporated. The residue was dissolved in 30 mL DCM, 5.69 g (49.9 mmol) TFA was added and the mixture was stirred at room temperature for 15 h. Ice-water was added and the pH was adjusted to 12 with NaOH aq. and stirred for 15 min The organic layer was separated and washed with brine and the aqueous layer was extracted with DCM. The combined organic layers were dried with Na2SO4, filtered and evaporated. The residue was taken up on isolute and subjected to purification by chromatography on silica eluting with a gradient formed from DCM, methanol and NEt3 to yield after evaporation of the product containing fractions 0.83 g (53%) of the title compound as light yellow oil. MS m/e: 315.1 [M+H]+.

Workup

  1. additionThe mixture was poured on ice-water
  2. extractionextracted with TBME
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. dissolutionThe residue was dissolved in 30 mL DCM
  8. stirringthe mixture was stirred at room temperature for 15 h
  9. stirringstirred for 15 min The organic layer
  10. customwas separated
  11. washwashed with brine
  12. extractionthe aqueous layer was extracted with DCM
  13. dry with materialThe combined organic layers were dried with Na2SO4
  14. filtrationfiltered
  15. customevaporated
  16. customsubjected to purification by chromatography on silica eluting with a gradient
  17. customformed from DCM, methanol and NEt3
  18. customto yield
  19. customafter evaporation of the product
  20. additioncontaining fractions 0.83 g (53%) of the title compound as light yellow oil

Sources & evidence

ORD record
ord-deb25b00eb8046af8cf5f6b6a8ee5c4b
Source dataset
uspto-grants-2013_12
Patent number
US08618303B2

Reaction notes

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