Pyridine, hydrofluoride (1:1) → benzyl (3R,4R)-3-fluoro-4-hydroxypyrrolidine-1-carboxylate

HRID 1095678Notes

Reaction equation

HRID 1095678 reaction equation
[CH:1]12[O:6][CH:5]1[CH2:4][N:3]([C:7]([O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:8])[CH2:2]2.N1C=CC=CC=1.[FH:23]>ClCCl>[F:23][C@H:1]1[C@H:5]([OH:6])[CH2:4][N:3]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH2:2]1

Participants

4

Reactant 2

HCID 64774Pyridine, hydrofluoride (1:1)HCID 22147363Benzyl 6-oxa-3-azabicyclo(3.1.0)hexane-3-carboxylate

Product 1

HCID 58395845benzyl (3R,4R)-3-fluoro-4-hydroxypyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

benzyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate (10.5 g, 47.9 mmol) and pyridine-hydrogen fluoride (14.2 g, 144.0 mmol) were added to a Teflon bottle containing dichloromethane and stirred vigorously overnight. After 20 hours, the reaction was slowly and carefully quenched with excess saturated solution of NaHCO3 over several minutes and allowed to stir for one hour, and then the organic layer was isolated and washed with NaHCO3 and a solution of brine. The combined organic layers were dried over MgSO4, filtered and evaporated to yield an oil. This crude oil was purified on silica gel using ethyl acetate-hexane to produce 2.0 g (17% isolated yield) of the desired product as an oil.

Workup

  1. waitAfter 20 hours
  2. customcarefully quenched with excess saturated solution of NaHCO3 over several minutes
  3. stirringto stir for one hour
  4. customthe organic layer was isolated
  5. washwashed with NaHCO3
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customto yield an oil
  10. customThis crude oil was purified on silica gel
  11. customto produce

Sources & evidence

ORD record
ord-9df46c480cf64015a18911afd8e91e6f
Source dataset
uspto-grants-2012_03
Patent number
US08138181B2

Reaction notes

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