Carbon Dioxide → 2-(4-Chloro-7-methylquinazolin-2-yl)-phenol

HRID 2406165Notes

Reaction equation

HRID 2406165 reaction equation
B(Br)(Br)Br.[Cl:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([CH3:16])=[CH:13][CH:14]=2)[N:9]=[C:8]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[O:23]C)[N:7]=1.C(=O)=O>ClCCl.C([O-])(O)=O.[Na+]>[Cl:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([CH3:16])=[CH:13][CH:14]=2)[N:9]=[C:8]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[OH:23])[N:7]=1

Participants

6

Reactant 3

HCID 280Carbon DioxideHCID 25134Boron tribromideHCID 592128574-Chloro-2-(2-methoxy-phenyl)-7-methyl-quinazoline

Product 1

HCID 1361050322-(4-Chloro-7-methylquinazolin-2-yl)-phenol

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

Boron tribromide in dichloromethane (1 M, 900 mL, 900 mmol) was added drop wise to a cooled (−30-−40° C.) solution of 4-chloro-2-(2-methoxyphenyl)-7-methylquinazoline (93.2 g, 328 mmol) in dichloromethane (2 L) under nitrogen atmosphere. The resulting mixture was left warming to room temperature in about four hours and was slowly poured in 4 L sat. aq. NaHCO3. Stirring was continued until no more CO2 was produced. The layers were separated and the organic layer was dried over sodium sulfate, filtered, and evaporated to dryness under reduced pressure, yield: 90 g. The residue was filtered over a short plug of silica with dichloromethane as the eluent. Yield: 57.9 g (65%) of 2-(4-chloro-7-methylquinazolin-2-yl)phenol (1H-NMR, LC-MS: >90% purity). It was found that the only impurity still present was the corresponding bromo quinazoline (LC-MS, M+found=271 [M+1]; 315, 317 [M-Cl+Br], Br-isotope patterns present).

Workup

  1. waitThe resulting mixture was left
  2. customwas produced
  3. customThe layers were separated
  4. dry with materialthe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated to dryness under reduced pressure, yield: 90 g
  7. filtrationThe residue was filtered over a short plug of silica with dichloromethane as the eluent

Sources & evidence

ORD record
ord-dc44e90264934c9ab3081c2cf2376e21
Source dataset
uspto-grants-2014_08
Patent number
US08809353B2

Reaction notes

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