Phosphorus oxychloride → 4-Chloro-6,6-dimethyl-5,6,7,8-tetrahydroquinazoline

HRID 240997Notes

Reaction equation

HRID 240997 reaction equation
[CH3:1][C:2]1([CH3:13])[CH2:11][CH2:10][C:9]2[N:8]=[CH:7][NH:6][C:5](=O)[C:4]=2[CH2:3]1.P(Cl)(Cl)([Cl:16])=O>C(Cl)(Cl)Cl>[Cl:16][C:5]1[C:4]2[CH2:3][C:2]([CH3:13])([CH3:1])[CH2:11][CH2:10][C:9]=2[N:8]=[CH:7][N:6]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 1357423376,6-Dimethyl-3,4,5,6,7,8-hexahydroquinazolin-4-one

Product 1

HCID 866478114-Chloro-6,6-dimethyl-5,6,7,8-tetrahydroquinazolineYield 75%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To 6,6-dimethyl-5,6,7,8-tetrahydroquinazolin-4(3H)-one (6.41 g, 36 mmol) in chloroform (10 mL) added phosphorus oxychloride (10 mL) and refluxed for 2 hours. The mixture was concentrated to an oil, then diluted with ethyl acetate (80 mL) and washed with saturated sodium carbonate (50 mL) and brine (25 mL). The solution was dried over anhydrous sodium sulfate, filtered and concentrated, then the residue purified by silica gel column chromatography (ethyl acetate/hexanes, 1:8) to give 4-chloro-6,6-dimethyl-5,6,7,8-tetrahydroquinazoline (5.3 g, 75% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3): 8.72 (s, 1H), 2.52 (t, 2H), 2.14 (s, 2H), 1.48 (t 2H), 0.93 (s, 6H); MS (EI) for C10H13ClN2: 197 (MH+).

Workup

  1. temperaturerefluxed for 2 hours
  2. concentrationThe mixture was concentrated to an oil
  3. additiondiluted with ethyl acetate (80 mL)
  4. washwashed with saturated sodium carbonate (50 mL) and brine (25 mL)
  5. dry with materialThe solution was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customthe residue purified by silica gel column chromatography (ethyl acetate/hexanes, 1:8)

Sources & evidence

ORD record
ord-032ef48705184554a0eeedffe1217a7a
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

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