(Diethylamino)sulfur trifluoride → (3R,4S)-3-azidomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine

HRID 859887Notes

Reaction equation

HRID 859887 reaction equation
[N:1]([CH2:4][C@@H:5]1[C@@H:9](O)[CH2:8][N:7]([C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])[CH2:6]1)=[N+:2]=[N-:3].C(N(S(F)(F)[F:27])CC)C.C(=O)([O-])O.[Na+]>ClCCl>[N:1]([CH2:4][C@@H:5]1[C@H:9]([F:27])[CH2:8][N:7]([C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])[CH2:6]1)=[N+:2]=[N-:3]

Participants

5

Reactant 3

HCID 123472(Diethylamino)sulfur trifluoride2×HCID 516892Sodium BicarbonateHCID 86600232(3R,4R)-3-azidomethyl-1-benzyloxycarbonyl-4-hydroxypyrrolidine

Product 1

HCID 86600236(3R,4S)-3-azidomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Process (A): (3R,4R)-3-Azidomethyl-1-benzyloxycarbonyl-4-hydroxypyrrolidine (1.20 g) was dissolved in dichloromethane (40 mL). While this solution was cooled on a sodium chloride/ice bath, diethylaminosulfur trifluoride (1.20 mL) was added dropwise and the mixture was stirred at room temperature for 3 hours. The reaction vessel was again cooled on a sodium chloride/ice bath and diethylaminosulfur trifluoride (0.57 mL) was again added dropwise. The mixture was then stirred at room temperature for 2 hours. While the reaction mixture was cooled on an ice bath, a saturated aqueous solution of sodium hydrogen carbonate (40 mL) was added dropwise and the dichloromethane layer was separated. The dichloromethane layer was sequentially washed with a saturated aqueous solution of sodium hydrogen carbonate (2×20 mL) and water (20 mL), followed by drying over anhydrous sodium sulfate and concentration under reduced pressure. The resulting residue was purified on a silica gel column (eluant=hexane:ethyl acetate=2:1) to give 726 mg of (3R,4S)-3-azidomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine as a pale brown oil.

Workup

  1. temperatureWhile this solution was cooled on a sodium chloride/ice bath
  2. temperatureThe reaction vessel was again cooled on a sodium chloride/ice bath
  3. stirringThe mixture was then stirred at room temperature for 2 hours
  4. temperatureWhile the reaction mixture was cooled on an ice bath
  5. customthe dichloromethane layer was separated
  6. washThe dichloromethane layer was sequentially washed with a saturated aqueous solution of sodium hydrogen carbonate (2×20 mL) and water (20 mL)
  7. dry with materialby drying over anhydrous sodium sulfate and concentration under reduced pressure
  8. customThe resulting residue was purified on a silica gel column (eluant=hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-05361371fb3949209be58089b57a0480
Source dataset
uspto-grants-2006_12
Patent number
US07153851B2

Reaction notes

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