5-Methoxytetralone → HCID 10264769, compound

HRID 1727270Notes

Reaction equation

HRID 1727270 reaction equation
C[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10]([OH:12])=[CH:9][CH:8]=[CH:7]2.C[O:14][C:15]1C=C[CH:22]=[C:21]2[C:16]=1[CH2:17]CC[C:20]2=[O:25].[CH3:26][Mg]Br>>[CH3:26][C:5]1[C:6]2[CH:7]=[CH:8][C:9]3[C:17]4[O:25][CH:20]=[C:21]([CH3:22])[C:16]=4[C:15](=[O:14])[O:12][C:10]=3[C:11]=2[CH:2]=[CH:3][CH:4]=1

Participants

4

Reactant 3

HCID 366205-MethoxytetraloneHCID 122037931-Hydroxy-8-methylnaphthaleneHCID 178418573HCID 178418573, compound

Product 1

HCID 10264769HCID 10264769, compound

Procedure

Neo-tanshinlactone (1) was synthesized by a 8-step sequence, as illustrated in Scheme 1. Our synthetic strategy was to first prepare 8-methyl-1-naphthol (6). Accordingly, 5-methoxy-1-tetralone (2) was reacted with methylmagnesium bromide, and without purification, the resulting crude product (3) was dehydrated using concentrated HCl (Y.-G. Suh et al., Chem. Commun., 1203-1204 (2000); P. Mayer et al., Heterocycles, 55(2), 387-392 (2000)). The product 4, after purification, was dehydrogenated over 10% Pd/C in refluxing triglyme to furnish compound 5. Demethylation of 5 with BBr3 gave the desired naphthol intermediate 6 after silica gel chromatography. The total yield over for the four steps (2→6) was 70%. Treatment of 6 with malonic acid in the presence of PPA at 75° C. yielded 7 (H. Kamijo et al., Nippon Kagaku Kaishi, 11, 1257-1262 (1993)). Reaction of 7 with chloroacetone under basic conditions in DMF, followed by reaction with PPA at 110° C. gave the target product 1. (Y.-L. Chen et al., Helvetica Chimica Acta, 79, 651-657 (1996) B. Rajitha et al., Indian J. Chem., 25B, 872-873 (1986))

Workup

  1. customwithout purification
  2. customThe product 4, after purification
  3. temperaturein refluxing triglyme

Sources & evidence

ORD record
ord-c83d15f027d840f4a819731de9feb813
Source dataset
uspto-grants-2009_02
Patent number
US07495026B2

Reaction notes

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