3-Methyl-2-butenoic acid → Dihydrocoumarin

HRID 654838

Reaction equation

HRID 654838 reaction equation
BrC1C=C(O)C=CC=1.[Br:9][C:10]1[CH:19]=[C:18]2[C:13]([CH2:14][CH2:15][C:16](=[O:20])[O:17]2)=[CH:12][CH:11]=1.CC(C)=CC(O)=O.[H-].[Na+].[C:30]1([O:36][C:37](=[O:40])[CH:38]=[CH2:39])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>[Al+3].[Cl-].[Cl-].[Cl-].C(Cl)Cl.O1CCCC1>[Br:9][C:10]1[CH:19]=[C:18]2[C:13]([CH2:14][CH2:15][C:16](=[O:20])[O:17]2)=[CH:12][CH:11]=1.[O:40]=[C:37]1[CH2:38][CH2:39][C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[O:36]1

Participants

10

Reactant 5

HCID 109313-Methyl-2-butenoic acidHCID 115633-Bromophenol6×HCID 24758Sodium hydrideHCID 61242Phenyl acrylate2×HCID 200832517-Bromochroman-2-one2×

Product 2

HCID 660DihydrocoumarinHCID 200832517-Bromochroman-2-one

Reagents, catalysts & solvents 3

HCID 6451240Aluminum(III) ChlorideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Thus, in accordance with Reaction Scheme 6, 3-bromo phenol, or a 3-bromo phenol substituted in the 4 (para) position by an alkyl substituent (Compound 7) is acylated with an acylating agent, such as the acid chloride (compound 11) derived from 3,3-dimethylacrylic acid or from another appropriately substituted acrylic acid (R1 ' and R2 ' is either H or lower alkyl). The acylation of the 3-bromo-phenol (Compound 7) with the acid chloride (Compound 11) is preferably conducted in the presence of a strong base (e.g. sodium hydride) in an inert solvent (such as tetrahydrofuran). The resulting phenyl-acrylate (Compound 12) is ring closed under Friedel-Crafts type reaction conditions (e.g. AlCl3 catalyst, in an inert solvent such as methylene chloride) to provide two positional isomers (Compound 13) and (Compound 14) of the 2-oxo-chroman derivative, each of which bears, in the 4-position, the CH2R1 ' and CH2R2 ' substituents and where R5 is hydrogen or lower alkyl. As described previously for Reaction Scheme 5, the mixture is then separated by conventional means to obtain the desired 7-bromo-2-oxo-chroman (Compound 13). 1t should be noted that as also described previously in connection with Reaction Scheme 5 the 7-bromo-2-oxo chroman (Compound 11) can be separated from the potential regio-isomeric impurities at the carboxylic acid stage or at the final coupling stage. The 2-oxo-7-bromo-chroman (Compound 13) is thereafter reduced with lithium aluminum hydride or an appropriate reducing agent to provide the 7-bromo-diol (Compound 15). The diol (Compound 15) is then mono-mesylated at the primary alcohol position followed by intramolecular nucleophilic displacement of a mesyl leaving group, to give the 7-bromo-chroman (Compound 8) which bears the desired CH2 --R1', CH2R2 ' and R5 substituents. The carboxylic acid function is introduced into the 7-position in the same manner as described previously in Reaction scheme 5 to give the 7-carboxy chroman (Compound 10).

Sources & evidence

ORD record
ord-e047e01f36c649568b5777fe7cd7abb2
Source dataset
uspto-grants-1992_07
Patent number
US05134159

Linked notes

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