Phosphorus oxychloride → 7-(Benzyloxy)-4-chloro-6-methoxyquinazoline

HRID 871398Notes

Reaction equation

HRID 871398 reaction equation
[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13](O)=[N:14][CH:15]=[N:16]2)=[CH:11][C:10]=1[O:20][CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:24])=O>C1(C)C=CC=CC=1>[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([Cl:24])=[N:14][CH:15]=[N:16]2)=[CH:11][C:10]=1[O:20][CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178486768HCID 178486768, compound

Product 1

HCID 106619987-(Benzyloxy)-4-chloro-6-methoxyquinazolineYield 72%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

A stirred mixture of 7-(benzyloxy)-6-methoxyquinazolin-4-ol (5.10 g, 18.09 mmol) and phosphorous oxychloride (10 mL, 109 mmol) in dry toluene (30 mL), was heated to 120° C. for 2 h. After cooling to room temperature the mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (200 mL) and washed with sat aqueous NaHCO3 solution (2×100 mL). The organic layer was separated and dried over MgSO4 then concentrated under reduced pressure to afford 7-(benzyloxy)-4-chloro-6-methoxyquinazoline as a cream solid (3.89 g, 72%) which was taken into the next step without further purification. 1H NMR (300 MHz, CDCl3) δ 8.85 (s, 1H), 7.49 (m, 2H), 7.33-7.43 (m, 5H), 5.33 (s, 2H), 4.07 (s, 3H); LC-MS (ESI) m/z 301 (M+H)+.

Workup

  1. temperatureAfter cooling to room temperature the mixture
  2. concentrationwas concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in ethyl acetate (200 mL)
  4. washwashed
  5. customThe organic layer was separated
  6. dry with materialdried over MgSO4
  7. concentrationthen concentrated under reduced pressure

Sources & evidence

ORD record
ord-2282ffb0330e4639a64339aaaafe250d
Source dataset
uspto-grants-2015_03
Patent number
US08969587B2

Reaction notes

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