(4R)-4-methyl-15-alkenyl-6-hexadecanone derivatives, synthesis method and use thereof in synthesizing musk ketone

(4R)-4-methyl-15-alkenyl-6-hexadecanone derivatives, synthesis method and use thereof in synthesizing musk ketone

  • CN 101,239,895 B
  • Filed: 02/20/2008
  • Issued: 04/10/2013
  • Est. Priority Date: 02/20/2008
  • Status: Active Grant
First Claim
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1. the synthetic method of (4R)-4-methyl-15-thiazolinyl-6-16 ketone derivatives is characterized in that by step 1)~

  • 5) synthetic;

    1) ice bath under the nitrogen protection, is dissolved in 209mg compound 2 in the anhydrous diethyl ether, slowly be added drop-wise in the Li-Al hydrogen anhydrous diethyl ether, wherein, Li-Al hydrogen 57mg, room temperature reaction 3h, reaction solution is added drop-wise to cancellation in the sodium sulfate ether of crystal water, diatomite filtration is with ether washing, organic phase anhydrous sodium sulfate drying, concentrated, column chromatography gets 180mg compound 3;

    2) room temperature under the nitrogen protection, is added drop-wise to compound 3 with 3.9ml methoxymethyl chlorine, in diisopropyl ethyl amine and the methylene dichloride, wherein, compound 35.8g and propyl group ethylamine 8.0ml, room temperature reaction 5 hours, dichloromethane extraction, merge organic phase, saturated sodium-chloride is washed, anhydrous sodium sulfate drying, concentrated, column chromatography gets 6.7g compound 4a;

    Perhaps room temperature under the nitrogen protection, is added drop-wise to compound 3 with 5.02g t-Butyldimethylsilyl chlorine, in imidazoles and the DMF, wherein, compound 35g and imidazoles 2.45g, room temperature reaction spends the night, and ether extraction merges organic phase, saturated sodium-chloride is washed, anhydrous sodium sulfate drying, concentrated, column chromatography gets 7.37g compound 4b;

    3) cryosel is bathed, and under the argon shield, 1.0g compound 4a is dissolved in dry ether, slowly be added drop-wise to Li is housed, the glycol dibromide of catalytic amount, in the there-necked flask of dry ether, wherein, Li 94mg, contain 0.5%Na among the Li, drip and finish, low temperature stirs 2h,-78 ℃

    , under the argon shield, above-mentioned freshly prepd lithium reagent is added drop-wise in the Weinreb acid amides 10 and dry ether of undecylenic acid, wherein, the Weinreb acid amides 100.51g of undecylenic acid drips complete, naturally rises to room temperature, ethyl acetate extraction, organic phase washes with water respectively, saturated ammonia chloride is washed, and saturated sodium-chloride is washed, anhydrous sodium sulfate drying, concentrated, column chromatography gets 0.53g compound 5a;

    Perhaps cryosel is bathed, and under the argon shield, 2.0g compound 4b is dissolved in dry ether, slowly be added drop-wise to Li is housed, the glycol dibromide of catalytic amount, in the there-necked flask of dry ether, wherein, Li 142mg, contain 0.5%Na among the Li, drip and finish, low temperature stirs 2h,-78 ℃

    , under the argon shield, above-mentioned freshly prepd lithium reagent is added drop-wise to the Weinreb acid amides 10 of undecylenic acid, in the ether of drying, wherein, the Weinreb acid amides 100.78g of undecylenic acid drips complete, naturally rise to room temperature, ethyl acetate extraction, organic phase washes with water respectively, and saturated ammonia chloride is washed, saturated sodium-chloride is washed, anhydrous sodium sulfate drying, concentrated, column chromatography gets 0.909g compound 5b;

    4) 3.2g compound 5a is dissolved in the methyl alcohol, add the 0.5ml concentrated hydrochloric acid, oil bath heating, back flow reaction 6h, rotary evaporation is removed methyl alcohol, ethyl acetate extraction, organic phase washes with water respectively, and saturated sodium bicarbonate is washed, saturated sodium-chloride is washed, anhydrous sodium sulfate drying, concentrated, column chromatography gets 2.7g colourless liquid 6;

    Perhaps 2g compound 5b is dissolved in the tetrahydrofuran (THF), adds 3.2g tetrabutyl ammonium fluoride stirred overnight at room temperature, ethyl acetate extraction, organic phase washes with water respectively, and saturated sodium-chloride is washed, anhydrous sodium sulfate drying, concentrated, column chromatography gets 1.3g colourless liquid 6;

    5) under the nitrogen protection, the 0.24ml oxalyl chloride is dissolved in CH 2Cl 2In, be chilled to-78 ℃ and

    slowly add the 0.4ml dimethyl sulfoxide (DMSO) in the solution of methylene dichloride ,-78 ℃

    of lower stirrings 1 hour, add 0.5g compound 6 in the solution of methylene dichloride ,-78 ℃

    of lower stirrings 1 hour add 2ml triethylamine cancellation reaction under the low temperature, continue stirring and rise to room temperature after 15 minutes, add entry, tell organic phase, the water dichloromethane extraction, merge organic phase, saturated sodium-chloride is washed, anhydrous sodium sulfate drying, concentrated, column chromatography gets 0.46g compound 7;

    In the above-mentioned reaction, compound 2~

    5, colourless liquid 6, the structure of compound 7,10 is;

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