Formation of 2-hydroxy-7-methoxy-5-methyl-1-naphthoic acid: The naphthoate portion of neocarzinostatin; 2-hydroxy-7-methoxy-5-methyl-1-naphthoic acid

lisa frost (kafs4@sussex.ac.uk),
A contribution from the Caddick Group, Sussex

Chemicals Used
2-hydroxy-7-methoxy-5-methyl-1-naphthoic acid methyl ester [SyntheticPage 175] Sodium hydroxide (Avocado) Methanol (GPR) Water

Procedure
To a solution of 2-hydroxy-7-methoxy-5-methyl-1-naphthoic acid methyl ester (2.0 g, 8.1 mmol, 1 equiv) in methanol: water (111 mL:37 mL) was added NaOH (755 mg, 19 mmol, 2 equiv). The reaction was set to reflux for 24 h, after which it was cooled to room temperature and the methanol removed in vacuo. The resulting brown solution was acidified to pH 1 and the creamy suspension extracted into DCM (3 x 100 mL), dried (MgSO₄), filtered and concentrated in vacuo yielding the title compound as a fawn coloured solid. (1.2 g, 63%)

Author's Comments
This reaction works well and yields the required carboxylic acid in moderate yield. The purity of the acid formed is such that no chromatography is required. When purification of the acid was attempted, the yield of this process was seen to be dramatically reduced.

Data
1H nmr (300 MHz, CH₃OD) 8.25 (1H, d, J = X.X Hz), 8.05 (1H, d, J = X.X Hz), 7.00 (1H, d, J = X.X Hz), 6.92 (1H, d, J = X.X Hz), 3.9X (3H, s), 2.65 (3H, s).

Lead Reference
Rucker, Mark; Brueckner, Reinhard; Syn.Lett.; 10; 1997; 1187-1189.

Other References

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