Iodine → Pyridine, 4-ethyl-2-fluoro- (9CI)

HRID 342885Notes

Reaction equation

HRID 342885 reaction equation
[CH2:1]([C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1)[CH3:2].II.[F:11]F.C(=O)(O)[O-].[Na+]>S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+]>[F:11][C:5]1[CH:4]=[C:3]([CH2:1][CH3:2])[CH:8]=[CH:7][N:6]=1

Participants

6

Reactant 4

HCID 807IodineHCID 108224-EthylpyridineHCID 24524Fluorine2×HCID 516892Sodium Bicarbonate

Product 1

HCID 639436Pyridine, 4-ethyl-2-fluoro- (9CI)

Reagents, catalysts & solvents 1

HCID 656671Sodium PyrosulfiteSolvent

Procedure

A solution containing 4-ethylpyridine (12.8 g, 120 mmol) and iodine (30.5 g, 120 mmol) in CF2ClCFCl2 (150 ml) was placed in a fluorination apparatus fitted with a drying tube filled with soda lime. Elemental fluorine (165 mmol) as a 10% mixture in dry nitrogen was then passed through the stirred solution using narrow bore PTFE tubing at ca. 40 ml/min. After the fluorine had been added the solution was poured into 10% aqueous sodium metabisulfite solution (300 ml), neutralised with solid sodium bicarbonate and extracted with dichloromethane. The organic extracts were dried and evaporated to a yellow oil (9.54 g) which contained ethlpyridine (78 % conversion), 2-fluoropyridine and other minor products by GC/MS. The oil redissolved in dichloromethane and washed with 2N HCI solution, dried (MgSO4) and evaporated to a clear oil to give 2-fluoro-4-ethylpyridine in >95% purity (6.3 g, 54% based on 78% conversion); δH (200 MHz, CDCl3, Me4Si) 1.26 ppm (3H, t, J 7.6, CH3), 2.69 (2H, q, J 7.6, CH2), 6.75 (1H, s, H-3), 7.02 (1H, d m, J 5.1, H-5), 8.09 (1H, d, J 5.1, H-6); δC (50 MHz, CDCl3, Me4Si) 14.1 ppm (s, CH3), 28.2 (d, 4JC-F 2.7, CH2), 108.5 (d, 2JC-F 36.5, C-3), 121.3 (d, 4JC-F 3.9, C-5), 147.3 (d, 3JC-F 15.2, C-6), 159.3 (d, 3JC-F 7.8, C-4), 164.2 (d, 1JC-F 236.3, C-2); δF (235 MHz, CDCl3, CFC13) 69.9 ppm (s); m/z (E1+125 (M+, 100%), 110 (47), 97 (15), 83 (13).

Workup

  1. customfitted with a drying tube
  2. extractionextracted with dichloromethane
  3. customThe organic extracts were dried
  4. customevaporated to a yellow oil (9.54 g) which
  5. dissolutionThe oil redissolved in dichloromethane
  6. washwashed with 2N HCI solution
  7. dry with materialdried (MgSO4)
  8. customevaporated to a clear oil

Sources & evidence

ORD record
ord-9a4893d6d3754ca3bae165004c59bb5d
Source dataset
uspto-grants-1999_01
Patent number
US05859255

Reaction notes

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