Thionyl Chloride → 2-Bromo-6-[(3-fluoro-4-methoxybenzoyl)amino]-4-methoxyphenyl 3-fluoro-4-methoxybenzoate

HRID 858233Notes

Reaction equation

HRID 858233 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][CH3:12])[C:5]([OH:7])=[O:6].S(Cl)(Cl)=O.[NH2:17][C:18]1[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[C:20]([Br:26])[C:19]=1O>C(OCC)C.N1C=CC=CC=1.C(Cl)Cl.CN(C)C=O>[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][CH3:12])[C:5]([O:7][C:19]1[C:18]([NH:17][C:5](=[O:6])[C:4]2[CH:8]=[CH:9][C:10]([O:11][CH3:12])=[C:2]([F:1])[CH:3]=2)=[CH:23][C:22]([O:24][CH3:25])=[CH:21][C:20]=1[Br:26])=[O:6]

Participants

8

Reactant 3

HCID 24386Thionyl ChlorideHCID 27334013-Fluoro-4-methoxybenzoic acidHCID 111719822-Amino-6-Bromo-4-Methoxyphenol

Product 1

HCID 111799682-Bromo-6-[(3-fluoro-4-methoxybenzoyl)amino]-4-methoxyphenyl 3-fluoro-4-methoxybenzoateYield 97.1%

Reagents, catalysts & solvents 4

HCID 1049PyridineSolvent2×HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-fluoro-4-methoxybenzoic acid (39.0 g, 229 mmol), thionyl chloride (100 mL), and N,N-dimethylformamide (0.5 mL) was refluxed for 1 h. The volatiles were removed under vacuum. The solids were taken in benzene (twice) and the volatiles were removed under vacuum. The residue was dissolved in CH2Cl2(100 mL) and added into a cold (0° C.) mixture (mechanically stirred) of 2-amino-6-bromo-4-methoxyphenol (20.0 g, 91.7 mmol) and CH2Cl2 (150 mL). Anhydrous pyridine (37.0 mL, 468.5 mmol) was added dropwise into the new mixture. During the pyridine addition a precipitate was formed. The mixture was stirred for 30 min and then ethyl ether (250 mL) was added. The precipitated solids were filtered off and washed with ethyl ether. The solids were taken in water and stirred for 20 min. The solids were then filtered off and dried to give an off-white solid (46.5 g, 97% yield, m.p. 184–186° C.); MS m/e 520 (M−H)+.

Workup

  1. temperaturewas refluxed for 1 h
  2. customThe volatiles were removed under vacuum
  3. customwere removed under vacuum
  4. dissolutionThe residue was dissolved in CH2Cl2(100 mL)
  5. additionadded into a cold (0° C.) mixture (
  6. customwas formed
  7. filtrationThe precipitated solids were filtered off
  8. washwashed with ethyl ether
  9. stirringstirred for 20 min
  10. filtrationThe solids were then filtered off
  11. customdried

Sources & evidence

ORD record
ord-ea0f995f1a204ae3b7761f93ae1dade4
Source dataset
uspto-grants-2006_12
Patent number
US07148247B2

Reaction notes

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