Beta-Lapachone → HCID 178442263, compound

HRID 990271Notes

Reaction equation

HRID 990271 reaction equation
[CH3:1][C:2]1([CH3:18])[O:7][C:6]2[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=3[C:14]([C:16](=[O:17])[C:5]=2[CH2:4][CH2:3]1)=[O:15].OC1C(=O)C2C(C(=O)C=1)=CC=CC=2.BrCC=C(C)C.[I-].[Na+]>CS(C)=O.C(N(CC)CC)C>[CH3:1][C:2]([CH3:18])=[CH:3][CH2:4][C:5]1[C:6](=[O:7])[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=2[C:14](=[O:15])[C:16]=1[OH:17]

Participants

7

Reactant 4

HCID 3885Beta-Lapachone3×HCID 5238Sodium IodideHCID 700922-Butene, 1-bromo-3-methyl-HCID 178516607HCID 178516607, compound

Product 1

HCID 178442263HCID 178442263, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8471TriethylamineSolvent

Procedure

β-lapachone, as well as its intermediates, derivatives and analogs thereof (also referred to herein as the “active compounds”), are described in Li, C. J. et al., J Biol. Chem., 1993. Unlike prior art β-lapachone syntheses as illustrated in Scheme 1, the synthesis of β-lapachone, in accordance with the present invention and generally illustrated in Scheme 2, commences with the reaction of 2-hydroxy-1,4-naphthoquinone with 1-bromo-3-methyl-2-butene in the presence of sodium iodide and triethylamine (a weak base) in dimethylsulfoxide (DMSO) to produce lapachol in up to 40% yield, after purification (20 g, up to 40% overall yield). Lapachol is then quantitatively converted to β-lapachone by treatment with sulfuric acid. The β-lapachone is purified by recrystallization from ethanol.

Sources & evidence

ORD record
ord-0b140b40f6d442e492a2c4836e25922d
Source dataset
uspto-grants-2002_10
Patent number
US06458974B1

Reaction notes

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