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

HRID 2062325Notes

Reaction equation

HRID 2062325 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-670abb56bbad45a4bd370ebfcf19f903
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

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