Triethylamine → 4-Chloro-6-fluoroquinazoline

HRID 2225168Notes

Reaction equation

HRID 2225168 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][N:6]=[C:5]2O.P(Cl)(Cl)([Cl:15])=O.C(N(CC)CC)C>C(Cl)Cl>[Cl:15][C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([F:1])[CH:3]=2)[N:8]=[CH:7][N:6]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 24813Phosphorus oxychlorideHCID 178518010HCID 178518010, compound

Product 1

HCID 130594574-Chloro-6-fluoroquinazoline

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Preparation D2, Step 2: 6-fluoroquinazolin-4-ol (1.00 g, 6.09 mmol, 1 eq.), phosphorus oxychloride (3.41 mL, 36.6 mmol, 6 eq.) and triethylamine (5.09 mL, 36.6 mmol, 6 eq.) were mixed at room temperature and then refluxed for 2 hours. Worked up by stripping 3 times from methylene chloride. The residue was dissolved in methylene chloride (25 mL) and rinsed 3 times with saturated sodium bicarbonate (25 mL) and 1× with brine (25 mL). The organic layer was dried (sodium sulfate) and stripped to give a crude oil. Purified over silica gel in 9:1 to 3:1 hexanes/ethyl acetate. Obtained 4-chloro-6-fluoroquinazoline (0.96 g) as a tan solid. Yield=86%. LCMS detects (M+H)+=183.16.

Workup

  1. temperaturerefluxed for 2 hours
  2. washrinsed 3 times with saturated sodium bicarbonate (25 mL) and 1× with brine (25 mL)
  3. dry with materialThe organic layer was dried (sodium sulfate)
  4. customto give a crude oil
  5. customPurified over silica gel in 9:1 to 3:1 hexanes/ethyl acetate

Sources & evidence

ORD record
ord-0e45308eb8d5430bbf9f4af0a302c4ee
Source dataset
uspto-grants-2008_05
Patent number
US07378409B2

Reaction notes

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