Hydrochloric Acid → 2-Propanamidobenzoic acid

HRID 1827326Notes

Reaction equation

HRID 1827326 reaction equation
C(C1N(C2C=CC(F)=CC=2)[C:11](=[O:20])[C:10]2C(=[CH:6][CH:7]=[CH:8][CH:9]=2)N=1)C.O1[CH:26]=[CH:25][C:24](=[O:27])[N:23]=[CH:22]1.FC1C=CC(N)=CC=1.Cl.[OH2:37]>C(Cl)(Cl)Cl.CCCCCC.[OH-].[Na+].CC(C)=O>[C:24]([NH:23][C:22]1[CH:6]=[CH:7][CH:8]=[CH:9][C:10]=1[C:11]([OH:20])=[O:37])(=[O:27])[CH2:25][CH3:26]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 962WaterHCID 97314-FluoroanilineHCID 120180582-Ethyl-3-(4-fluorophenyl)-3H-quinazolin-4-oneHCID 187626094H-1,3-Oxazin-4-one2×

Product 1

HCID 32646742-Propanamidobenzoic acid

Reagents, catalysts & solvents 4

HCID 14798Sodium HydroxideCatalystHCID 180AcetoneSolventHCID 6212ChloroformSolventHCID 8058HexaneSolvent

Conditions

Temperature
145 °C

Procedure

2-Ethyl-3-(4-fluorophenyl)-3H-quinazolin-4-one (IV) A solution of 8.50 2-ethyl-benzo[d]1,3]oxazin-4-one (III) (48.5 mmol, 1.00 equiv) and 6.27 g 4-fluoroaniline (50.9 mmol, 1.05 equiv) dissolved in 35 mL chloroform was heated to reflux for 12 h, after which time TLC indicated no compound III remained (Rf=0.51, 20% acetone in hexane). The chloroform was removed in vacuo and the resulting solid suspended in 18 mL ethylene glycol. A catalytic amount of sodium hydroxide (86 mg, 2.2 mmol, 0.045 equiv) was added to the mixture, which was heated to 140 to 150° C. (external temperature, oil bath). After 10 h, the reaction was removed from heat and equilibrated to room temperature; upon cooling a precipitate formed. The cooled reaction product mixture was acidified with 2 mL aqueous 5% hydrochloric acid solution and suspended in 20 mL cold water. The solid was collected by vacuum filtration, rinsing with cold water (2×50 mL) and cold isopropyl alcohol (2×50 mL). The air-dried solid was recrystallized from isopropyl alcohol, affording 10.62 g tan-white needles. m.p. 178.3° C. 1H NMR (CDCl3) δ 1.25 (t, 3H, J=7.4 Hz), 2.46 (q, 2H, J=7.4 Hz), 7.26 (d, 2H, J=6.4 Hz), 7.27 (d, 2H, J=6.4 Hz), 7.48 (t, 1H, J=6.8 Hz), 7.73–7.81 (m, 2H), 8.27 (d, 1H, J=7.96 Hz) ppm. MS (ESI+) 269.1 [MH]+.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 12 h
  3. customThe chloroform was removed in vacuo
  4. customthe reaction was removed
  5. temperaturefrom heat
  6. customequilibrated to room temperature
  7. temperatureupon cooling a precipitate
  8. customformed
  9. customThe cooled reaction product mixture
  10. filtrationThe solid was collected by vacuum filtration
  11. washrinsing with cold water (2×50 mL) and cold isopropyl alcohol (2×50 mL)
  12. customThe air-dried solid was recrystallized from isopropyl alcohol

Sources & evidence

ORD record
ord-d243df637ade4733863a4f079bf1a832
Source dataset
uspto-grants-2006_05
Patent number
US07053215B2

Reaction notes

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