1-Bromo-2-Chloroethane → 4-Chloro-7-(2-bromoethoxy)-6-methoxyquinazoline

HRID 639970Notes

Reaction equation

HRID 639970 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([OH:14])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[Br:21][CH2:22][CH2:23]Cl.ClC1C2C(=CC(OCCCl)=C(OC)C=2)N=CN=1>CC(N(C)C)=O>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:23][CH2:22][Br:21])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 78491-Bromo-2-ChloroethaneHCID 11430Potassium CarbonateHCID 596829074-Chloro-7-(2-chloroethoxy)-6-methoxyquinazolineHCID 1357422514-Chloro-6-methoxyquinazolin-7-ol

Product 1

HCID 867610734-Chloro-7-(2-bromoethoxy)-6-methoxyquinazolineYield 73%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-chloro-6-methoxyquinazolin-7-ol (5.0 g, 24 mmol), potassium carbonate (9.94 g, 72 mmol) and 1-bromo-2-chloroethane (7.98 ml, 96 mmol) in dimethyl acetamide (50 ml) was heated at 90° C. for 3 hours. The reaction mixture was allowed to cool to room temperature and then filtered. The filtrate was purified directly by silica gel chromatography eluting with a 20 to 80% mixture of ethyl acetate in iso-hexane. The obtained product was triturated with diethyl ether to give a 3:1 mixture of 4-chloro-7-(2-chloroethoxy)-6-methoxyquinazoline: 4-chloro-7-(2-bromoethoxy)-6-methoxyquinazoline (4.77 g, 73% yield) as a white solid:

Workup

  1. temperatureto cool to room temperature
  2. filtrationfiltered
  3. customThe filtrate was purified directly by silica gel chromatography
  4. washeluting with a 20 to 80% mixture of ethyl acetate in iso-hexane
  5. customThe obtained product was triturated with diethyl ether
  6. customto give

Sources & evidence

ORD record
ord-ce0ba6e94d00449cacf1f02b6d081843
Source dataset
uspto-grants-2010_04
Patent number
US07691867B2

Reaction notes

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