1-Acetoxy-2-butyl-4-methoxynaphtalene

Originator

Bunaprolast,ZYF Pharm Chemical

Uses

Anti-asthmatic.

Manufacturing Process

Preparation of pentacarbonyl[phenyl(methoxy)carbene]chromium:
To a suspension of 22 g (0.1 mole) of chromium hexacarbonyl in ether is slowly added phenyllithium (51 ml, 0.1 mole, cyclohexane/ether solution) via syringe over a period of 15-20 minutes under argon at room temperature, and the resulting deep red solution is stirred at room temperature for 1 hour. The solvent is removed under reduced pressure (bath temperature should be below 40°C), and the black residue is dissolved in 200 ml water. (CH3)3O·BF4 (about 15 g) is added portionwise to the solution until it becomes slightly acidic (pH 5.5). The aqueous layer is extracted three times with 200 ml of ether, and the combined etheral extracts are washed once with 300 ml of saturated brine solution, once with 300 ml of saturated sodium carbonate solution, and three times with 300 ml of saturated brine solution, dried over anhydrous sodium sulfate and filtered. The solvent is removed using a rotary evaporator. The deep red tarry residue is purified using flash chromatography by a silica gel column (200 g). Elution by 10% ether in n-hexane gives a deep red syrup, which is solidified upon cooling. Recrystallization from pet-ether at -70°C gives 25.12 g (80.5%) of pentacarbonyl[phenyl(methoxy)carbene] chromium as deep red crystalline. The physical properties of the product are consistent with those described in the literature.
2-Butyl-4-methoxy-1-naphthalenol, acetate:
Reaction of pentacarbonyl[phenyl(methoxy)carbene ]chromium with 1- hexyne:
Part A.
A mixture of the carbene complex (1.0 g, 3.2 mmole), 1-hexyne (2.6 equivalents), acetic anhydride (1.0 eq.) and triethylamine (1.0 eq.) in tetrahydrofuran (90 ml) is heated at 65°C under an argon atmosphere for 1 hour. The solution is cooled and concentrated to give a black residue, which is chromatographed through a silica gel (200 g) column using a flash chromatography. Elution by10% ether in n-hexane gives 71 5 mg (82.2%) of the title product, which solidified. Recrystallization from pet-ether gave white crystals of 2-butyl-4-methoxy-1-naphthalenol acetate; MP: 49°C. Part B.
Alternatively, a mixture of 2.0 g (6.4 mmole) of the carbene complex, acetylene (2.6 eq.) and acetic acid in tetrahydrofuran is heated at 65°C for 2 hours under argon atmosphere. After cooling the reaction solution is concentrated and the black residue is loaded on a silica gel (200 g) column for a flash chromatography. Elution by 10% ether in n-hexane gives 895 mg (51.4%) of the title product.

Therapeutic Function

Anti-asthmatic

in vivo

IC 50

LTB₄; TXB₂; 5-LO