7-Bromo-4,4-dimethyl-1,2,3,4-tetrahydronaphthalen-1-one → (3-Bromophenyl)acetaldehyde

HRID 963855Notes

Reaction equation

HRID 963855 reaction equation
BrC1C=C2C(C(C)(C)CCC2=O)=CC=1.[Br:15][C:16]1[CH:17]=[C:18]([CH2:22][C:23](OCC)=[O:24])[CH:19]=[CH:20][CH:21]=1.[H-].C([Al+]CC(C)C)C(C)C>>[Br:15][C:16]1[CH:17]=[C:18]([CH2:22][CH:23]=[O:24])[CH:19]=[CH:20][CH:21]=1

Participants

4

Reactant 3

HCID 107533577-Bromo-4,4-dimethyl-1,2,3,4-tetrahydronaphthalen-1-oneHCID 11470552Ethyl 3-(bromophenyl)acetate2×HCID 21225700Diisobutylaluminumhydride

Product 1

HCID 20387554(3-Bromophenyl)acetaldehyde

Procedure

Compound G can be obtained as described in J. Med. Chem. 1995, 38, 4764-4767, and as shown in Reaction Scheme 1. Thus, referring now specifically to Reaction Scheme 1, ethyl 3-bromophenylacetate (Compound B, made by esterification of 3-bromophenylacetic acid) is reduced with diisobutylaluminum hydride (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). The isomeric compound, 6-bromo-3,4-dihydro-4,4-dimethylnaphthalen-1(2H)-one (Compound H) can be obtained, starting with ethyl (4-bromophenyl)acetate, in accordance with the sequence of reactions illustrated in Reaction Scheme 1 for Compound G. 6-Bromo-3,4-dihydro-4,4-dimethylnaphthalen-1(2H)-one (Compound H) can also be obtained in accordance with the published literature procedure: Mathur et al. Tetrahedron, 41, 1509-1516 (1985).

Workup

  1. custom1995, 38, 4764-4767, and as shown in Reaction Scheme 1

Sources & evidence

ORD record
ord-ba724ad95f14486ea84ae03a09f5cf9f
Source dataset
uspto-grants-1998_06
Patent number
US05763635

Reaction notes

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