2-Methoxybenzaldehyde → o-Anisalacetone

HRID 1642096Notes

Reaction equation

HRID 1642096 reaction equation
CC1NC2C[CH:9]([C:13]3[C:18]([O:19][CH3:20])=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH2:10][C:11](=[O:12])[C:5]=2C(C2C=CC=C(O)C=2)C=1C(OCCOC)=O.C(O)(=O)C.N.COC1C=CC=CC=1C=O.C(OCC)(=O)CC([O-])=O>CC(C)=O>[CH3:20][O:19][C:18]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[CH:9]=[CH:10][C:11](=[O:12])[CH3:5]

Participants

6

Reactant 4

HCID 86582-MethoxybenzaldehydeHCID 12432Ammonia acetateHCID 2926768ST0935532×HCID 3595298Propanedioic acid, monoethyl ester

Product 1

HCID 139181o-Anisalacetone

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

Synthesis of HPIs of the disclosure can be performed by any means by one of skill in the art. However, an example of synthesis of HPI-1 is provided. HPI-1 can be readily prepared in a one-pot synthesis using the Hantzsch reaction (Loev et al., J. Pharm. Pharmacol. (1972) 24:917-918) (see also FIG. 10 panel A-B). This synthetic transformation generates the dihydropyridyl pharmacophore from an aldehyde, two 1,3-diones, and ammonia acetate in high yields. First, one of the 1,3-diones was prepared in two synthetic steps (FIG. 10, panel A). 4-(2-methoxyphenyl)but-3-en-2-one was synthesized by an aldol condensation of 2-methoxybenzaldehyde and acetone, followed by dehydration. Reaction of the α,β-unsaturated ketone product with ethyl malonate generated an ester intermediate, which yielded the desired aryl-substituted 1,3-dione upon decarboxylation. HPI-1 was then synthesized by heating a mixture of the aryl-substituted 1,3-dione, 3-hydroxybenzaldehyde, 2-methoxyethyl acetoacetate, ammonium acetate, and the ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate (BMIM.BF4) (FIG. 10, panel B). Purification by silica gel chromatography yielded the final product as a mixture of four diastereomers in 63% overall yield. Using this procedure, it is possible to synthesize gram quantities of HPI-1, which would be sufficient for both research and clinical applications. HPI-1 derivatives set forth in Table II were similarly prepared.

Workup

  1. customSynthesis of HPIs of the disclosure
  2. customis provided
  3. customthe Hantzsch reaction (Loev et al., J. Pharm. Pharmacol. (1972) 24:917-918) (
  4. customFirst, one of the 1,3-diones was prepared in two synthetic steps (FIG. 10, panel A)

Sources & evidence

ORD record
ord-ca4d157c9b524a79a609051735db0091
Source dataset
uspto-grants-2012_02
Patent number
US08119640B2

Reaction notes

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