Triphenylphosphine → 4-Chloro-6-(2-fluoro-1-fluoromethyl-ethoxy)-quinazoline

HRID 2246266Notes

Reaction equation

HRID 2246266 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([OH:12])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:13][CH2:14][CH:15](O)[CH2:16][F:17].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])O.[Na+]>C1COCC1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH:15]([CH2:16][F:17])[CH2:14][F:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 679851,3-Difluoro-2-propanolHCID 516892Sodium BicarbonateHCID 231602734-Chloroquinazolin-6-ol

Product 1

HCID 231603724-Chloro-6-(2-fluoro-1-fluoromethyl-ethoxy)-quinazolineYield 74%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-Chloro-6-hydroxy-quinazoline (500 mg; 2.78 mmol), 800 mg (8.33 mmol) of 1,3-difluoro-2-propanol and 2.18 g (8.33 mmol) of triphenyl phosphine were dissolved in 30 ml of THF and 3.62 g (8.33 mmol) was added thereto at room temperature. The reaction solution was stirred at room temperature for 3 hours more, a saturated aqueous solution of sodium hydrogen carbonate was added and the mixture was extracted with chloroform. The organic layer was dried and concentrated and the resulting residue was purified by a silica gel column chromatography (hexane:ethyl acetate=1:2) to give 530 mg (yield: 74%) of 4-chloro-6-(2-fluoro-1-fluoromethyl-ethoxy)-quinazoline as a yellow solid.

Workup

  1. addition3.62 g (8.33 mmol) was added
  2. customat room temperature
  3. extractionthe mixture was extracted with chloroform
  4. customThe organic layer was dried
  5. concentrationconcentrated
  6. customthe resulting residue was purified by a silica gel column chromatography (hexane:ethyl acetate=1:2)

Sources & evidence

ORD record
ord-98ae73ca44dc4a96b2c702399f5a03c1
Source dataset
uspto-grants-2010_03
Patent number
US07687502B2

Reaction notes

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