Phosphorus oxychloride → HCID 86649060, compound

HRID 1801931Notes

Reaction equation

HRID 1801931 reaction equation
O[C:2]1[C:11]2[C:6](=[C:7]([CH3:12])[CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[N:3]=1.O=P(Cl)(Cl)[Cl:20]>CN(C=O)C>[Cl:20][C:2]1[C:11]2[C:6](=[C:7]([CH3:12])[CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[N:3]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178470309HCID 178470309, compound

Product 1

HCID 86649060HCID 86649060, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideCatalyst

Conditions

Temperature
80 °C

Procedure

A mixture of ethyl 4-hydroxy-8-methylquinazoline-2-carboxylate (330 mg, 1.39 mmol), POCl3 (20 mL), and DMF (3 drops) was stirred at 80° C. for 48 h. The mixture was concentrated under reduced pressure and the solid residue was partitioned between DCM (100 mL) and cold H2O (100 mL). The separated aqueous phase was extracted with DCM (2×100 mL) and the combined organic layers were dried over MgSO4, filtered, and concentrated. The residue was purified by silica gel chromatography eluting with EtOAc/hexanes to afford ethyl 4-chloro-8-methylquinazoline-2-carboxylate as a solid (320 mg, 90%). 1H NMR (300 MHz, DMSO-d6) δ1.39 (t, J=7.1 Hz, 3H), 2.76 (s, 3H), 4.45 (q, J=7.1 Hz, 2H), 7.90 (m, 1H), 8.1 (m, 1H), 8.2 (m, 1H).

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customthe solid residue was partitioned between DCM (100 mL) and cold H2O (100 mL)
  3. extractionThe separated aqueous phase was extracted with DCM (2×100 mL)
  4. dry with materialthe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with EtOAc/hexanes

Sources & evidence

ORD record
ord-a3599b8d238e4ccead8a49d73d97d799
Source dataset
uspto-grants-2013_01
Patent number
US08349851B2

Reaction notes

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