Phosphorus oxychloride → 4-(Benzyloxy)-2-chloropyridine

HRID 910888Notes

Reaction equation

HRID 910888 reaction equation
C(OC1C([Cl:15])=NC=CC=1)C1C=CC=CC=1.[CH2:16]([O:23][C:24]1[CH:29]=[CH:28][NH:27][C:26](=O)[CH:25]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.P(Cl)(Cl)(Cl)=O>>[CH2:16]([O:23][C:24]1[CH:29]=[CH:28][N:27]=[C:26]([Cl:15])[CH:25]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

4

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 8193743-(Benzyloxy)-2-chloropyridineHCID 36077244-Benzyloxy-2(1H)-pyridone

Product 1

HCID 534041974-(Benzyloxy)-2-chloropyridineYield 47.1%

Conditions

Temperature
90 °C

Procedure

Preparation of 4-(benzyloxy-2-chloropyridine: A 250 mL round-bottomed flask was charged with 4-(benzyloxy)pyridin-2(1H)-one (10.0 g, 49.7 mmol) and phosphorus oxychloride (55.6 mL, 596 mmol). The reaction mixture was heated at 90° C. overnight, then cooled and carefully quenched with sodium carbonate and sodium hydroxide to pH 7. The aqueous layer was extracted with dichloromethane. The organic layer was dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography with dichloromethane as eluent to afford 4-(benzyloxy)-2-chloropyridine (5.14 g, 47.1% yield) as white solid. 1H NMR (CDCl3) δ 8.19 (d, 1H), 7.34-7.44 (m, 5H), 6.91 (d, 1H), 6.81 (dd, 1H), 5.10 (s, 2H). LC/MS: (5 to 95) Rt=2.64 min (ESI) m/z=220 (M+H) (40%).

Workup

  1. temperaturecooled
  2. customcarefully quenched with sodium carbonate and sodium hydroxide to pH 7
  3. extractionThe aqueous layer was extracted with dichloromethane
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel column chromatography with dichloromethane as eluent

Sources & evidence

ORD record
ord-aaaad3885f7546839a5ff59f82469729
Source dataset
uspto-grants-2011_09
Patent number
US08022222B2

Reaction notes

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