Phosphorus oxychloride → HCID 86649061, compound

HRID 625791Notes

Reaction equation

HRID 625791 reaction equation
[F:1][C:2]([F:25])([C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=1)[C:3]1[N:12]=[C:11](O)[C:10]2[C:5](=[CH:6][C:7]([C:14]([O:16][CH3:17])=[O:15])=[CH:8][CH:9]=2)[N:4]=1.P(Cl)(Cl)([Cl:28])=O>>[Cl:28][C:11]1[C:10]2[C:5](=[CH:6][C:7]([C:14]([O:16][CH3:17])=[O:15])=[CH:8][CH:9]=2)[N:4]=[C:3]([C:2]([F:25])([F:1])[C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[N:12]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178497302HCID 178497302, compound

Product 1

HCID 86649061HCID 86649061, compoundYield 86%

Procedure

A mixture of methyl 2-(difluoro(4-fluorophenyl)methyl)-4-hydroxyquinazoline-7-carboxylate (1.1 g, 3.2 mmol) and phosphorus oxychloride (15 mL) was heated at reflux overnight. The mixture was concentrated under reduced pressure, and then toluene (20 mL) was added and evaporated under reduced pressure (2×). The residue in DCM was filtered through a pad of silica gel eluting with DCM. The filtrate was concentrated under reduced pressure to afford methyl 4-chloro-2-(difluoro(4-fluorophenyl)methyl)quinazoline-7-carboxylate (1 g, 86%). 1H NMR (300 MHz, DMSO-d6) δ 3.98 (s, 3H), 7.37 (t, 2H), 7.75 (t, 2H), 8.39 (d, 1H), 8.49 (s, 1H), 8.64 (d, 1H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight
  3. concentrationThe mixture was concentrated under reduced pressure
  4. additiontoluene (20 mL) was added
  5. customevaporated under reduced pressure (2×)
  6. filtrationThe residue in DCM was filtered through a pad of silica gel eluting with DCM
  7. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-e0b5980f8c1946f6afb423efb3dcf180
Source dataset
uspto-grants-2016_04
Patent number
US09308207B2

Reaction notes

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