Water → Phenylmethyl (3S)-3-fluoro-1-pyrrolidinecarboxylate

HRID 970198Notes

Reaction equation

HRID 970198 reaction equation
C(N(S(F)(F)[F:7])CC)C.O[C@@H:11]1[CH2:15][CH2:14][N:13]([C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])[CH2:12]1.O.C(=O)(O)[O-].[Na+]>ClCCl>[F:7][C@H:11]1[CH2:15][CH2:14][N:13]([C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])[CH2:12]1

Participants

6

Reactant 4

HCID 962WaterHCID 123472(Diethylamino)sulfur trifluorideHCID 516892Sodium BicarbonateHCID 11183628(R)-(-)-1-CBZ-3-pyrrolidinol

Product 1

HCID 15197579Phenylmethyl (3S)-3-fluoro-1-pyrrolidinecarboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

A 5-L, 3-neck, round bottom flask equipped with mechanical stirrer, thermocouple, addition funnel and nitrogen bubbler was charged with 375 mL (2.84 mol) of (diethylamino)sulfur trifluoride and 400 mL of dichloromethane. The solution was cooled to −78° C. To this was added via addition funnel a solution of 304 g (1.37 mol) of benzyl (3R)-3-hydroxypyrrolidine-1-carboxylate in 400 mL of dichloromethane over a 2-h period keeping the reaction temperature below −70° C. The reaction mixture was allowed to stir and warm slowly to ambient temperature overnight. The reaction mixture was added portion-wise with caution to a large extractor containing ice, water, and saturated aqueous sodium bicarbonate solution. The mixture was extracted with 8 L of ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, and concentrated to give a brown oil. Purification by flash chromatography (silica gel, eluting with a 10 to 30% ethyl acetate/hexane gradient) gave the title compound as a brown oil.

Workup

  1. additionthermocouple, addition funnel
  2. customthe reaction temperature below −70° C
  3. temperaturewarm slowly to ambient temperature overnight
  4. additionThe reaction mixture was added portion-wise with caution to a large extractor
  5. extractionThe mixture was extracted with 8 L of ethyl acetate
  6. washThe organic layer was washed with brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated
  9. customto give a brown oil
  10. customPurification by flash chromatography (silica gel
  11. washeluting with a 10 to 30% ethyl acetate/hexane gradient)

Sources & evidence

ORD record
ord-f3e8277f2d8742f3970af5d9be8328e2
Source dataset
uspto-grants-2007_12
Patent number
US07309714B2

Reaction notes

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