Structure of 153559-45-6
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CAS No. : | 153559-45-6 |
Formula : | C24H28O3 |
M.W : | 364.48 |
SMILES Code : | O=C(OC)C1=CC=C(C(C2=C(C)C=C3C(C)(C)CCC(C)(C)C3=C2)=O)C=C1 |
MDL No. : | MFCD12828199 |
InChI Key : | DYVLPJYIGJZAKF-UHFFFAOYSA-N |
Pubchem ID : | 11726298 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P280-P301+P312-P302+P352-P305+P351+P338 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With sodium amide In tetrahydrofuran | Rectangular plates of compound 35 were found suitable for X-ray diffraction, and a study was conducted. To complete the synthesis of bexarotene, the Friedel-Crafts acylation of 35, by crude mono-methyl-terephthaloyl chloride (36), gave ketone (37) which was converted to alkene ester(38) by a Wittig reaction, and ester 38 was saponified by potassium hydroxide followed by acidification with aqueous hydrochloric acid to give bexarotene (39) (Scheme 2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | Into a 50-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed PPh3MeBr (1715 mg, 4.80 mmol, 2.50 eq.), THF (10 ml_). This was followed by the addition of KHDMS (1 M) (5.1 ml_, 5.1 1 mmol, 2.66 eq.) dropwise with stirring at -30C. The resulting solution was stirred for 30 min at 0C. To this was added a solution of methyl 4-[(3, 5, 5, 8, 8-pentamethyl-5, 6, 7, 8-tetrahydronaphthalen-2-yl) carbonyl] benzoate (700 mg, 1.92 mmol, 1.00 eq.) in THF (7 ml_) dropwise with stirring at -30C. The resulting solution was stirred for 1 h at 0C. The reaction was then quenched by the addition of 20 ml_ of water at 0C. The resulting solution was extracted with 2x20 ml_ of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1 c20 ml_ of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1/10). This resulted in 480 mg (69%) of methyl 4-[1-(3, 5,5,8, 8-pentamethyl-5, 6,7,8- tetrahydronaphthalen-2-yl)ethenyl]benzoate as a light yellow solid. | |
66% | With sodium amide; In tetrahydrofuran; | Rectangular plates of compound 35 were found suitable for X-ray diffraction, and a study was conducted. To complete the synthesis of bexarotene, the Friedel-Crafts acylation of 35, by crude mono-methyl-terephthaloyl chloride (36), gave ketone (37) which was converted to alkene ester(38) by a Wittig reaction, and ester 38 was saponified by potassium hydroxide followed by acidification with aqueous hydrochloric acid to give bexarotene (39) (Scheme 2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | For comparison in the biological evaluation (Fig. 1 and 2) of compounds 1 - 3, [8 and 9] and 30-32, [8b and 9b] an authentic sample of bexarotene and its ketone analog (33a) were synthesized, following the reported route (Boehm, et al. "Synthesis and Structure-Activity Relationships of Novel Retinoid X Receptor-Selective Retinoids." J. Med. Chem. 1994, 37, 2930-2941 ): a seven step, convergent synthesis that gave a 29% overall yield of bexarotene. The first sequence of steps to bexarotene concerned the SN1 conversion of 2,5-dimethyl-2,5-hexanediol (33b) to 2,5-dichloro-2,5- dimthylhexane (34) by HCI, and the subsequent aluminum trichloride catalyzed Friedel-Crafts alkylation of toluene to give 1 ,2,3,4-tetrahydro-l .l A4,6-pentamethylnapthalene (35) in 68% yield over two steps (Scheme 1 ). | |
With potassium hydroxide; In methanol; | (b.) [4-(5,6,7,8-Tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)carbonyl]benzoic acid (31): To a suspension of the ester 30 (0.120 g, 0.329 mmol) in 75% aqueous methanol (2 mL) was added potassium hydroxide (0.055 g). The reaction mixture was stirred at 60 C. for 1 h during which time the material dissolved. The solution was cooled to room temperature, acidified with 1N aqueous hydrochloric acid, and then extracted with 80% ethyl acetate/hexane. The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated to afford a white solid (0.109 g). Recrystallization from benzene/hexane afforded 31 as a white, crystalline solid (0.102 g, 89%): m.p. 209-212 C. The structure of the product was also confirmed using IR, 1 H NMR and mass spectroscopy. | |
Example 6: Preparation of Impurity BTo a suspension of methyl [4-(5,6,7,8-tetrahydro-3, 5,5,8, 8-pentamethyl-2- naphthalenyl)carbonyl]benzoate (5 g) in methanol (200 ml), 5N potassium hydroxide solution (20 ml) was added at 25-30 C and heated to reflux. After completion of reaction (monitored by TLC), the reaction mixture was cooled to 20-25 C and acidified with 5N hydrochloric acid (20 ml). The solid, thus precipitated out, was stirred at 20-25 C for 1 hour, filtered, washed with water (50 ml) and dried at 60 C to give 3.1 g of the title compound as white solid having purity 99.52 % by HPLC. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 1: Preparation of methyl [4-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2- naphthalenyl)carbonyl]benzoateTo a solution of 4-carboxy benzoic acid (100 g) in dichloromethane (800 ml) under nitrogen gas atmosphere, phosphorous pentachloride (200 g) was added at 25-30 C and temperature was slowly raised to 38-44 C. After completion of the reaction (monitored by GC), the reaction mass was cooled to -5 to -10 C. Thereafter aluminium chloride (340g) and l,2,3,4,-tetrahydro-l-l,4,4,6-pentamethyl naphthalene (120 g) were successively added to the reaction mixture and heated slowly to 38-44C and refluxed for 1 hour. After completion of reaction (monitored by TLC), the reaction mass was cooled to 15-20 C and poured into 5N hydrochloric acid (1L). Layers were separated and aqueous layer was extracted with dichloromethane (600 ml). The combined organic layer was washed successively with demineralized water (2 L) and sodium bicarbonate solution (8 % solution, 1600 ml)) The resulting organic layer was distilled off at atmospheric pressure to give residue which was dried to give title compound having purity 98.58 %, impurity A: 0.52 % and keto acid impurity B: 0.22 % by HPLC. Purification:n-Heptane (400 ml) was added to the resulting product and stirred for 30 minutes. The mixture is then cooled to 5-10 C, stirred for 1 hour and filtered. The solid, thus obtained, is slurry washed with cold n- heptane (200 ml) and dried at 65C to give 173 g of title compound as white to off white crystalline powder having purity 99.75%, impurity A: 0.14 % and keto acid impurity B: 0.02% by HPLC. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 2: Preparation of methyl 4-[l-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2- naphthalenyl)-l-ethenyl]benzoateTo a suspension of methyl triphenylphosphonium bromide (167 g) in toluene (1000 ml) under nitrogen gas atmosphere at 25-30C, potassium hexamethyldisilazide in toluene (0.5 M, 760 ml) was added. The solution was heated to 45-50C, stirred for 30-45 minutes and then cooled to 0-5C. A solution of methyl [4-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)carbonyl]benzoate (100 g), dissolved in toluene (600 ml) was slowly added to the reaction mixture and stirred for 2 hours. After completion of the reaction (monitored by HPLC), reaction mixture was poured into 2N hydrochloric acid (1 L). Layers were separated and aqueous layer was extracted with toluene (300 ml). The combined organic layer was washed with water (2 L). Activated carbon (0.05 g) was added to the resulting organic layer and stirred for 15 minutes at 25-30 C. Resulting reaction mass was filtered through hyflo. The filtrate was distilled off under vacuum at 50-55C to give title compound which was stirred in methanol (1 L) to remove triphenylphosphine oxide. The resulting product was filtered and dried to give 80 g of title compound having purity 95.65%, impurity C: 0.56 %, Impurity D: 1.90 %; Impurity E: 0.31%; impurity F: 0.22% by HPLC. |
Tags: 153559-45-6 synthesis path| 153559-45-6 SDS| 153559-45-6 COA| 153559-45-6 purity| 153559-45-6 application| 153559-45-6 NMR| 153559-45-6 COA| 153559-45-6 structure
A123065 [153559-46-7]
4-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydronaphthalene-2-carbonyl)benzoic acid
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A116458 [116047-26-8]
Methyl 8-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate
Similarity: 0.86
A551972 [144464-66-4]
Methyl 5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate
Similarity: 0.86
A214157 [114621-78-2]
2-(4-(3-Methylheptan-3-yl)benzoyl)benzoic acid
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A592589 [898764-26-6]
2'-Carboethoxy-3,3-dimethylbutyrophenone
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A116458 [116047-26-8]
Methyl 8-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate
Similarity: 0.86
A551972 [144464-66-4]
Methyl 5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate
Similarity: 0.86
A592589 [898764-26-6]
2'-Carboethoxy-3,3-dimethylbutyrophenone
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A507798 [812690-22-5]
Methyl 1-methyl-5,6,7,8-tetrahydronaphthalene-2-carboxylate
Similarity: 0.83
A123065 [153559-46-7]
4-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydronaphthalene-2-carbonyl)benzoic acid
Similarity: 0.89
A116458 [116047-26-8]
Methyl 8-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate
Similarity: 0.86
A551972 [144464-66-4]
Methyl 5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate
Similarity: 0.86
A214157 [114621-78-2]
2-(4-(3-Methylheptan-3-yl)benzoyl)benzoic acid
Similarity: 0.85
A592589 [898764-26-6]
2'-Carboethoxy-3,3-dimethylbutyrophenone
Similarity: 0.85
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