Boron tribromide → 2-(4-Chloro-6-fluoroquinazolin-2-yl)phenol

HRID 2079409Notes

Reaction equation

HRID 2079409 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=2)[N:5]=[C:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[O:19]C)[N:3]=1.B(Br)(Br)Br.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=2)[N:5]=[C:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[OH:19])[N:3]=1

Participants

5

Reactant 3

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 58683904HCID 58683904, compound

Product 1

HCID 1361214352-(4-Chloro-6-fluoroquinazolin-2-yl)phenolYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 4-chloro-6-fluoro-2-(2-methoxyphenyl)quinazoline (3.0 g, 10.39 mmol) in CH2Cl2 (15 mL) was cooled to −78° C. To it was added a 1.0 M BBr3 solution in CH2Cl2 (52 mL, 52 mmol) dropwise. The reaction was allowed to warm to room temperature. It was neutralized with a saturated aqueous NaHCO3 solution, and the aqueous layer was extracted twice with CH2Cl2. The combined organic layers were dried over MgSO4, filtered, and concentrated. Purification via silica gel chromatography using 5-20% CH2Cl2/hexanes gave 2-(4-chloro-6-fluoroquinazolin-2-yl)phenol (1.68 g, 60%). LC/MS: m/z 275.3 (M+H)+ at 3.39 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. extractionthe aqueous layer was extracted twice with CH2Cl2
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-d1a32f7d75ea4fc79dfe4faeff4b2ea4
Source dataset
uspto-grants-2011_04
Patent number
US07928107B2

Reaction notes

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