P-Cresol → 6-Methyl-4-phenyl-3,4-dihydrochromen-2-one

HRID 899559Notes

Reaction equation

HRID 899559 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([OH:24])=[C:6]([C@@H:8]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:9][CH2:10]N(C(C)C)C(C)C)[CH:7]=1.C(O)(=[O:34])/C=C/C1C=CC=CC=1.C1C(O)=CC=C(C)C=1>S(=O)(=O)(O)O>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[O:24][C:10](=[O:34])[CH2:9][CH:8]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:6]=2[CH:7]=1

Participants

5

Reactant 3

HCID 2879P-CresolHCID 443879TolterodineHCID 444539Cinnamic Acid

Product 1

HCID 37916436-Methyl-4-phenyl-3,4-dihydrochromen-2-one

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent

Procedure

U.S. Pat. No. 5,922,914 provides an alternate method for the preparation of tolterodine. The process involves the cyclization of trans-cinnamic acid with p-cresol in hot sulfuric acid to give 3,4-dihydro-6-methyl-4-phenyl-2H-benzopyran-2-one, which is reduced with diisobutyl aluminum hydride (DIBAL) in toluene to yield 6-methyl-4-phenyl-3,4-dihydro-2H-1-benzopyran-2-ol. This on reducto-condensation with diisopropylamine, by means of hydrogen over palladium on charcoal in methanol, affords racemic tolterodine of Formula I, which is resolved with L-(+)-tartaric acid.

Workup

  1. custom5,922,914 provides an alternate method

Sources & evidence

ORD record
ord-c7408fbb53964a01a81693675187eb38
Source dataset
uspto-grants-2008_04
Patent number
US07355077B2

Reaction notes

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