Imidazole → 2-fluoro-5-(4-(iodomethyl)tetrahydro-2H-pyran-4-yl)pyridine

HRID 595929Notes

Reaction equation

HRID 595929 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[I:20]I.N1C=CN=C1.[F:27][C:28]1[N:33]=[CH:32][C:31]([C:34]2([CH2:40]O)[CH2:39][CH2:38][O:37][CH2:36][CH2:35]2)=[CH:30][CH:29]=1>ClCCl>[F:27][C:28]1[CH:29]=[CH:30][C:31]([C:34]2([CH2:40][I:20])[CH2:39][CH2:38][O:37][CH2:36][CH2:35]2)=[CH:32][N:33]=1

Participants

6

Reactant 4

HCID 795ImidazoleHCID 807IodineHCID 11776TriphenylphosphineHCID 118045465(4-(6-fluoropyridin-3-yl)tetrahydro-2H-pyran-4-yl)methanol

Product 1

HCID 1180452242-fluoro-5-(4-(iodomethyl)tetrahydro-2H-pyran-4-yl)pyridineYield 60.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To an ice cooled solution of triphenylphosphine (983 mg, 3.75 mmol), iodine (952 mg, 3.75 mmol) in dichloromethane (20 mL) was added imidazole (278 mg, 4.09 mmol). The solution was stirred at ambient temperature for 1 h, followed by the addition of (4-(6-fluoropyridin-3-yl)tetrahydro-2H-pyran-4-yl)methanol (360 mg, 1.70 mmol) in 10 mL dichloromethane. The reaction mixture was heated to 60° C. in an oil bath for 48 h. Solid was filtered off, the filtrate was purified by flash column chromatography on silicagel (ISCO) eluting with 0-80% ethyl acetate in heptane to give to give 2-fluoro-5-(4-(iodomethyl)tetrahydro-2H-pyran-4-yl)pyridine (330 mg, 1.03 mmol, 60.3% yield) as light yellow color oil. LCMS (m/z): 322 (MH+), 0.77 min.

Workup

  1. temperatureThe reaction mixture was heated to 60° C. in an oil bath for 48 h
  2. filtrationSolid was filtered off
  3. customthe filtrate was purified by flash column chromatography on silicagel (ISCO)
  4. washeluting with 0-80% ethyl acetate in heptane
  5. customto give

Sources & evidence

ORD record
ord-e518d87dac2c480bbca8c40730fb90c5
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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