Phosphorus oxychloride → 1-Chloro-6-methoxy-4-methylphthalazine

HRID 1471351Notes

Reaction equation

HRID 1471351 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=O)[NH:8][N:7]=[C:6]2[CH3:14].O=P(Cl)(Cl)[Cl:17]>>[Cl:17][C:9]1[C:10]2[C:5](=[CH:4][C:3]([O:2][CH3:1])=[CH:12][CH:11]=2)[C:6]([CH3:14])=[N:7][N:8]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 155226156-Methoxy-4-methyl-2H-phthalazin-1-one

Product 1

HCID 593731221-Chloro-6-methoxy-4-methylphthalazineYield 100%

Conditions

Temperature
120 °C

Procedure

A solution of 6-methoxy-4-methyl-2H-phthalazin-1-one (6) (2.0 g, 10.5 mmol) in POCl3 (20 mL) is heated at reflux (120° C.) for 4 h and then cooled to room temperature. Unreacted POCl3 is removed at reduced pressure, followed by azeotroping with toluene (2×10 mL). The residue is diluted with sat. NaHCO3 (75 mL) and extracted with dichloromethane (150 mL, 2×60 mL, and 50 mL). The extract is washed (brine) and dried. After solvent removal at reduced pressure, the residue is dried under high vacuum to give 2.2 g (100%) of 7 as a yellow solid, mp 123-126° C. IR 2991, 1611, 1403, 1290, 1234 cm−1; 1H NMR (CDCl3) δ 2.95 (s, 3H, CH3), 4.05 (s, 3H, CH3O), 7.25 (d, J=1.2 Hz, 1H, 5-PhthH), 7.55 (dd, J=6.0, 1.2 Hz, 1H, 7-PhthH), 8.21 ppm (d, J=6.0 Hz, 1H, 8-PhthH).

Workup

  1. temperaturecooled to room temperature
  2. customUnreacted POCl3 is removed at reduced pressure
  3. customby azeotroping with toluene (2×10 mL)
  4. additionThe residue is diluted with sat. NaHCO3 (75 mL)
  5. extractionextracted with dichloromethane (150 mL, 2×60 mL, and 50 mL)
  6. washThe extract is washed (brine)
  7. customdried
  8. customAfter solvent removal at reduced pressure
  9. customthe residue is dried under high vacuum

Sources & evidence

ORD record
ord-a3fd8ca50eec490f8419b262003fbe8f
Source dataset
uspto-grants-2015_04
Patent number
US09012217B2

Reaction notes

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