2,5-Dibromopyridine → 1206912-74-4

HRID 626981Notes

Reaction equation

HRID 626981 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.C([Li])CCC.[O:14]1[CH2:19][CH2:18][C:17](=[O:20])[CH2:16][CH2:15]1>C1(C)C=CC=CC=1>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([C:17]2([OH:20])[CH2:18][CH2:19][O:14][CH2:15][CH2:16]2)=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 693532,5-DibromopyridineHCID 121599Tetrahydro-4H-pyran-4-oneHCID 178418339Butyllithium

Product 1

HCID 451048631206912-74-4Yield 33.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 2,5-dibromopyridine (1 g, 4.22 mmol) in anhydrous toluene (15 mL) was cooled to −78° C. with stirring under nitrogen. n-Butyllithium (2.5M solution in hexanes, 1.7 mL) was added dropwise over 10 minutes. The reaction mixture was stirred at −78° C. for 1 h, then tetrahydro-4H-pyran-4-one (0.43 mL, 4.66 mmol) was added slowly. The reaction mixture was allowed to warm to ambient temperature, then stirred for 2 h. The reaction mixture was quenched with saturated aqueous ammonium chloride solution (20 mL) and extracted into ethyl acetate (2×20 mL). The combined organic phases were dried over sodium sulfate and concentrated under vacuum. The resulting pale brown oil (983 mg) was purified by chromatography on silica (Biotage, 25 g cartridge), eluting with 0-60% ethyl acetate in heptanes. The resulting yellow solid (578 mg) was re-purified by chromatography on silica (Biotage, 10 g cartridge), eluting with 0-50% ethyl acetate in heptanes, to afford the title compound (363 mg, 32.3%) as a yellow solid. δH (500 MHz, DMSO-d6) 8.60 (d, J 2.2 Hz, 1H), 7.86 (dd, J 8.4, 2.3 Hz, 1H), 7.31 (d, J 8.4 Hz, 1H), 4.67 (s, 1H), 3.98 (td, J 11.7, 1.8 Hz, 2H), 3.94-3.89 (m, 2H), 2.11 (td, J 12.7, 5.5 Hz, 2H), 1.56 (d, J 12.2 Hz, 2H). Method B HPLC-MS: MH+ m/z 258/260, RT 1.44 minutes.

Workup

  1. stirringThe reaction mixture was stirred at −78° C. for 1 h
  2. stirringstirred for 2 h
  3. customThe reaction mixture was quenched with saturated aqueous ammonium chloride solution (20 mL)
  4. extractionextracted into ethyl acetate (2×20 mL)
  5. dry with materialThe combined organic phases were dried over sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe resulting pale brown oil (983 mg) was purified by chromatography on silica (Biotage, 25 g cartridge)
  8. washeluting with 0-60% ethyl acetate in heptanes
  9. customThe resulting yellow solid (578 mg) was re-purified by chromatography on silica (Biotage, 10 g cartridge)
  10. washeluting with 0-50% ethyl acetate in heptanes

Sources & evidence

ORD record
ord-502e9a9931eb4edab9eaa9606d255c0d
Source dataset
uspto-grants-2016_04
Patent number
US09309243B2

Reaction notes

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