Reaction #487582

Reaction equation

1,2-bis(bromomethyl)benzene

sodium methoxide

dimethyl 3-oxopentanedioate

→

benzo[7]annulene

Solvents

THF MeOH

Conditions

Workup

1. 1
   OtherAccordingly, compounds of formula (Ca) are prepared
2. 2
   Otheras set forth above in REACTION SCHEME 2B
3. 3
   workup.ADDITIONmade in situ via careful addition (e.g., at low temperature) of the appropriate metal to at least the protic solvent

Procedure

Accordingly, compounds of formula (Ca) are prepared, as set forth above in REACTION SCHEME 2B, by first combining a pentane-3-dioate, e.g. dimethyl 3-oxopentanedioate shown, with a 1,2-bismethyl aromatic having a suitable leaving group on each methyl group, e.g., 1,2-bis(bromomethyl)benzene, in a mixed protic/aprotic solvent medium, e.g., THF-MeOH, and a metal alkoxide, e.g., sodium methoxide. The metal alkoxide can be added as such or made in situ via careful addition (e.g., at low temperature) of the appropriate metal to at least the protic solvent, preferably prior to combination with the remaining reactants. The intermediate benzo[7]annulene product so formed can be optionally isolated and may contain one or two carboxy ester groups depending on the reaction conditions, e.g., methyl 7-oxo-6,7,8,9-tetrahydro-5H-benzo[7]annulene-6,8-dicarboxylate, as shown above. The intermediate, dimethyl 7-oxo-6,7,8,9-tetrahydro-5H-benzo[7]annulene-6,8-dicarboxylate, is subjected to basic hydrolysis (saponification) conditions followed by acidification to give compounds of formula (Ca).

Source