Acetic acid, 2-(triphenylphosphoranylidene)-, ethyl ester → Ethyl 4-(3-bromophenyl)butanoate

HRID 439644Notes

Reaction equation

HRID 439644 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH2:8][CH:9]=O)[CH:5]=[CH:6][CH:7]=1.[C:11]([CH:16]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([O:13][CH2:14][CH3:15])=[O:12]>>[Br:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][CH2:16][C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 2

HCID 70670Acetic acid, 2-(triphenylphosphoranylidene)-, ethyl esterHCID 20387554(3-Bromophenyl)acetaldehyde

Product 1

HCID 11492759Ethyl 4-(3-bromophenyl)butanoate

Procedure

In the preferred compounds of the invention the two R1 substituents are methyl, and the R2 and R3 substituents are hydrogen. Reaction Scheme 2 illustrates a synthetic process for preparing 7-bromo-3,4-dihydro-4,4-dimethylnaphthalen-1-one (Compound G) which serves as a starting material for the synthesis of several preferred compounds of the invention. Thus, referring now specifically to Reaction Scheme 2, ethyl 3-bromophenylacetate (Compound B, made by esterification of 3-bromophenylacetic acid) is reduced with diisobutylaluminumhydride (DIBAL-H) to yield (3-bromophenyl)acetaldehyde. (3-Bromophenyl)acetaldehyde is reacted in a Wittig reaction with (carbethoxymethylene)triphenylphosphorane to provide a mixture of E and Z ethyl 4-(3-bromophenyl)but-2-enoates. The latter compounds are hydrogenated to yield ethyl 4-(3-bromophenyl)butanoate (Compound D). Compound D is reacted with the Grignard reagent derived from methylbromide to give the tertiary alcohol 5-(3-bromophenyl)-2-methylpentan-2-ol (Compound E) (It should be apparent to those skilled in the art, that the choice of the Grignard reagent used in this reaction step determines the nature of the R1 substituent in the resulting compounds of the invention.) Compound E is then treated with acid to cyclize it and to form 6-bromo-1,2,3,4-tetrahydro-1,1-dimethylnaphthalene (Compound F). Compound F is oxidized with chromium trioxide to yield 7-bromo-3,4-dihydro-4,4-dimethylnaphthalen-1(2H)-one (Compound G). Compound G is covered by Formula 10 and in accordance with Reaction Schemes 1 and 3 serves as a starting material in the synthesis of several preferred compounds of the invention.

Workup

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Sources & evidence

ORD record
ord-c9e245cfe53943a49c8fba6082b4e7a0
Source dataset
uspto-grants-1996_05
Patent number
US05514825

Reaction notes

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