Trifluoroacetic acid → (R)-5-fluoro-2-methoxy-3-(pyrrolidin-2-yl)pyridine

HRID 1426889Notes

Reaction equation

HRID 1426889 reaction equation
C(O)(C(F)(F)F)=O.[F:8][C:9]1[CH:10]=[C:11]([C@H:17]2[CH2:21][CH2:20][CH2:19][N:18]2C(OC(C)(C)C)=O)[C:12]([O:15][CH3:16])=[N:13][CH:14]=1>C(Cl)Cl>[F:8][C:9]1[CH:10]=[C:11]([C@H:17]2[CH2:21][CH2:20][CH2:19][NH:18]2)[C:12]([O:15][CH3:16])=[N:13][CH:14]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86691710(R)-tert-butyl 2-(5-fluoro-2-methoxypyridin-3-yl)pyrrolidine-1-carboxylate

Product 1

HCID 66847680(R)-5-fluoro-2-methoxy-3-(pyrrolidin-2-yl)pyridineYield 49%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A DCM (12 mL) solution of TFA (11.3 mL, 146 mmol) was added to (R)-tert-butyl 2-(5-fluoro-2-methoxypyridin-3-yl)pyrrolidine-1-carboxylate (4.33 g, 14.6 mmol) and stirred at ambient temperature for 1 hour. The reaction was then concentrated, taken up in EtOAc, then washed with NaHCO3 and brine. The organic phase was dried (MgSO4), filtered, and concentrated, and the crude material was purified by silica column chromatography eluting with a 1-2% 7 N NH3-MeOH/DCM to afford (R)-5-fluoro-2-methoxy-3-(pyrrolidin-2-yl)pyridine as a liquid (1.40 g, 49% yield).

Workup

  1. concentrationThe reaction was then concentrated
  2. washwashed with NaHCO3 and brine
  3. dry with materialThe organic phase was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customthe crude material was purified by silica column chromatography
  7. washeluting with a 1-2% 7 N NH3-MeOH/DCM

Sources & evidence

ORD record
ord-123073c02652447eb7defd9f4b7ef9fb
Source dataset
uspto-grants-2015_01
Patent number
US08933084B2

Reaction notes

Loading…