(Diethylamino)sulfur trifluoride → (2R,4R)-1-tert-butyl 2-methyl 4-fluoropyrrolidine-1,2-dicarboxylate

HRID 732357Notes

Reaction equation

HRID 732357 reaction equation
C(N(S(F)(F)[F:7])CC)C.[CH3:10][O:11][C:12]([C@H:14]1[CH2:18][C@H:17](O)[CH2:16][N:15]1[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[O:13]>ClCCl>[CH3:10][O:11][C:12]([C@H:14]1[CH2:18][C@@H:17]([F:7])[CH2:16][N:15]1[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[O:13]

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 69512011-tert-Butyl 2-methyl (2R,4S)-4-hydroxypyrrolidine-1,2-dicarboxylate

Product 1

HCID 68687525(2R,4R)-1-tert-butyl 2-methyl 4-fluoropyrrolidine-1,2-dicarboxylateYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add (diethylamino)sulfur trifluoride (10.5 mL, 80 mmol) to a −78° C. cooled solution of 4-(S)-hydroxypyrrolidine-N1,2-(R)-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (9.83 g, 40 mmol) in dichloromethane (60 mL). Stir 2 h, then remove cooling bath and stir 18 h at room temperature. Heat to reflux for 30 min, then cool in ice bath and add saturated aqueous sodium bicarbonate solution. Warm to room temperature, dry (magnesium sulfate), concentrate (350 mbar, 25° C.) and purify (silica gel chromatography, eluting with diethyl ether and dichloromethane) and then concentrate at 120 mbar at 25° C. to give the title compound as an oil (9.09 g, 92%).

Workup

  1. customremove
  2. temperaturecooling bath
  3. stirringstir 18 h at room temperature
  4. temperatureHeat
  5. temperatureto reflux for 30 min
  6. temperaturecool in ice bath
  7. additionadd saturated aqueous sodium bicarbonate solution
  8. dry with materialdry (magnesium sulfate)
  9. concentrationconcentrate (350 mbar, 25° C.)
  10. custompurify
  11. wash(silica gel chromatography, eluting with diethyl ether and dichloromethane)
  12. concentrationconcentrate at 120 mbar at 25° C.

Sources & evidence

ORD record
ord-3d81d51bc04a4f5d9fadcfadc685dc74
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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