Picolyl chloride → HCID 66718431, compound

HRID 876955Notes

Reaction equation

HRID 876955 reaction equation
[H-].[Na+].[OH:3][C@H:4]1[CH2:8][CH2:7][O:6][CH2:5]1.Cl[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=1>C1COCC1>[O:6]1[CH2:7][CH2:8][C@H:4]([O:3][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=2)[CH2:5]1

Participants

5

Reactant 3

HCID 23393Picolyl chlorideHCID 24758Sodium hydrideHCID 2733227(S)-(+)-3-Hydroxytetrahydrofuran

Product 1

HCID 66718431HCID 66718431, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 3-neck flask under a nitrogen-line was charged with anhydrous THF (600 mL) through a canule. NaH (60% dispersion in mineral oil, 21.16 g, 0.529 mol, 1.5 eq) was suspended in the solvent under vigorous stirring. (S)-(+)-3-hydroxytetrahydrofuran (34.14 g, 0.388 mol., 1.1 eq) was added and stirred at room temperature for 30 minutes. 2-Chloromethylpyridine (1a; 45.00 g, 0.353 mol, 1 eq) was added neat and the mixture was stirred at reflux for 16 hours. The reaction mixture was cooled to room temperature and quenched with 520 mL saturated aqueous ammonium chloride solution. THF was removed under reduced pressure and the aqueous residue was extracted with 2×800 mL ethyl acetate. The combined organic extracts were washed with 250 mL saturated brine, dried over Na2SO4 and evaporated to dryness. The brown oily residue was taken up in 520 mL acetonitrile and remaining mineral oil was extracted with 330 mL hexane. Acetonitrile was evaporated in vacuo to leave a brown residue, yield 87%; LC-MS Retention time 1.22 min; (M+H)+ 180.

Workup

  1. stirringthe mixture was stirred
  2. temperatureat reflux for 16 hours
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customquenched with 520 mL saturated aqueous ammonium chloride solution
  5. customTHF was removed under reduced pressure
  6. extractionthe aqueous residue was extracted with 2×800 mL ethyl acetate
  7. washThe combined organic extracts were washed with 250 mL saturated brine
  8. dry with materialdried over Na2SO4
  9. customevaporated to dryness
  10. extractionwas extracted with 330 mL hexane
  11. customAcetonitrile was evaporated in vacuo
  12. customto leave a brown residue, yield 87%

Sources & evidence

ORD record
ord-287ecff24b624f988710645db7d85360
Source dataset
uspto-grants-2015_03
Patent number
US08987279B2

Reaction notes

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