| 摘要 |
Process for preparing 5,6-diphenyl-8,9-dihydro-7H-benzocycloheptene derivatives (A) from 3-methoxybenzaldehyde via new 2-aryl-5-phenyl-pentadienoic acid, 2-aryl-5-phenyl-pentanoic acid and benzocycloheptanone derivative intermediates (IX), (VIII), (III) and (II). Preparation of benzocycloheptene derivatives of formula (A) comprises: (i) reacting 3-methoxybenzaldehyde and acetaldehyde in presence of basic catalyst to give 3-methoxy-cinnamaldehyde, followed by Knoevenagel condensation with an arylacetic acid of formula ArCH2COOH (X); (ii) catalytically hydrogenating the obtained 2-aryl-5-phenyl-pentadienoic acid derivative of formula (IX); (iii) reacting the obtained 2-aryl-5-phenyl-pentanoic acid derivative of formula (VIII) with polyphosphoric acid; (iv) reacting the obtained benzo-cycloheptanone derivative of formula (V) with a sulfonylating agent of formula RSO2Nu (VI) in an aprotic solvent in presence of (in)organic base; (v) subjecting the obtained sulfonyloxy-benzocycloheptene compound of formula (III) to palladium-catalyzed reaction (Suzuki coupling) with a phenylboronic acid derivative of formula (IV); (vi) de-etherifying the obtained methoxy-benzocycloheptene derivative of formula (II) using a reagent (R1) consisting of boron tribromide and 2,6-dimethyl-pyridine; and (vii) converting the obtained 6-aryl-5-phenyl-8,9-dihydro-7H-benzocyclohepten-2-ol of formula (I) into (A) as described in WO2000003979. Ar = aromatic or heteroaromatic residue (optionally carrying 1-3 substituents); R = perfluorinated 1-8C n-alkyl (preferably CF3, C4F9 or C8F17); Nu = leaving group such as F, Cl, I or RSO2; X = Cl or Br; L = 2-10C linear or branched alkylene; Note: SK, R1 and R2 are groups described in WO2000003979 (not specifically defined in the present patent). Independent claims are also included for: (1) stages (i)-(vi) of the overall process as individual processes for preparing (IX), (VIII), (V), (III), (II) and (I) respectively; (2) (II), (III), (VIII) and (IX) as new compounds; (3) the reagent (R1); and (4) the use of (R1) for the selective cleavage of aromatic methyl ethers under mild conditions, specifically where higher ether groups in the starting compound are unaffected.
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