2-Methoxynaphthalene → 3-Phenoxyphenyl ethyl ketone

HRID 2163599

Reaktionsgleichung

Reaktionsgleichung von HRID 2163599
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)C=[C:8](C(C)C(C1C=CC=CC=1)=O)[CH:7]=[CH:6]2.CO[C:25]1[CH:26]=[C:27]2C(=[CH:33][CH:34]=1)C=CC=C2.C(Cl)(=[O:38])CC.[Cl-].[Al+3].[Cl-].[Cl-].C(C(C1C=CC2C(=CC=C(OC)C=2)C=1)=O)C.C(OC)(OC)OC.C(C(C1C=CC=C(O)C=1)=O)C.C1(Br)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl>[CH2:7]([C:6]([C:5]1[CH:10]=[CH:11][CH:12]=[C:3]([O:2][C:1]2[CH:27]=[CH:26][CH:25]=[CH:34][CH:33]=2)[CH:4]=1)=[O:38])[CH3:8]

Komponenten

11

Edukt 9

HCID 71192-MethoxynaphthaleneHCID 7961BromobenzeneHCID 9005Trimethyl orthoformateHCID 11430Potassium CarbonateHCID 62324Propionyl chlorideHCID 759131-(6-Methoxy-2-naphthalenyl)-1-propanoneHCID 831413'-HydroxypropiophenoneHCID 6451240Aluminum(III) ChlorideHCID 706061826-Methoxy-2-naphthyl propiophenone

Produkt 1

HCID 108679943-Phenoxyphenyl ethyl ketone

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

For the preparation of the preferred aryl alkyl ketones, a Friedel-Crafts reaction can be used, e.g., to effect reaction according to the following general format ##STR7## wherein R" is the residue of the desired aryl (Ar) group and R1 is the residue of the carboxylic acyl halide. For example, the 6-methoxy-2-naphthyl propiophenone can be prepared by reacting 6-methoxynaphthalene with propionyl chloride in the presence of aluminum chloride in methylene chloride. The resulting 6-methoxy-2-naphthyl ethyl ketone is converted to the methyl enol ether starting material for this process by reacting it with trimethyl orthoformate in the presence of acid and heating in vacuo. The 3-phenoxyphenyl ethyl ketone methyl enol ether can be prepared by reacting 3-hydroxyphenyl ethyl ketone with phenyl bromide in the presence of potassium carbonate to form 3-phenoxyphenyl ethyl ketone and then reacting this ketone with trimethylorthoformate to form the ketal followed by heating with acid. The enol ether of 2-fluoro-4-biphenylyl ethyl ketone is formed by reacting 2-fluoro-4-biphenylyl ethyl ketone with trimethylorthoformate to form the ketal, then heating with p-toluenesulfonic acid in vacuo. The 2-fluoro-4-biphenylyl ethyl ketone can be prepared from 4-bromopropiophenone via 4'-bromo-3'-nitropropiophenone (See Chemical Abstracts, 61, p. 8232g), 4-propionyl-2-nitrobiphenyl (Ullman reaction), 4-propionyl-2-aminobiphenyl (reduction) and finally the Schiemann Reaction. See U.S. Patent No. 3,793,457, Example 1, for a similar synthesis of 2-fluoro-4-biphenylyl methyl ketone. The difluorobiphenyl ketone can be prepared by reacting 4-cyano-2,2'-difluorobiphenyl with ethyl magnesium bromide to form the difluoro biphenylyl ethyl ketone. See U.S. Pat. No. 3,755,427. This ketone can be converted to the enol ether by the procedure described above. A preferred method for preparing the enol ether for preparing ibuprofen esters according to this invention is set forth in the detailed examples below.

Aufarbeitung

  1. customa Friedel-Crafts reaction
  2. customreaction
  3. temperatureheating in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-e6c4522a7e2746c0a24eb3fbf6769a39
Quelldatensatz
uspto-grants-1979_01
Patentnummer
US04135051

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