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Chemical Structure| 1169768-28-8 Chemical Structure| 1169768-28-8
Chemical Structure| 1169768-28-8

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Dlin-MeOH is a lipid.

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Product Details of Dlin-MeOH

CAS No. :1169768-28-8
Formula : C37H68O
M.W : 528.94
SMILES Code : CCCCC/C=C\C/C=C\CCCCCCCCC(O)CCCCCCCC/C=C\C/C=C\CCCCC
MDL No. :MFCD32062843

Safety of Dlin-MeOH

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319
Precautionary Statements:P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330

Application In Synthesis of Dlin-MeOH

* 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.

  • Downstream synthetic route of [ 1169768-28-8 ]

[ 1169768-28-8 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 4102-60-7 ]
  • [ 109-94-4 ]
  • [ 1169768-27-7 ]
  • [ 1169768-28-8 ]
YieldReaction ConditionsOperation in experiment
1.9 g; 78% Synthesis of Compound 6bTo a flame dried 500 mL RB flask, freshly activated Mg turnings (2.4 g, 100 mmol) were added and the flask was equipped with a magnetic stir bar, an addition funnel and a reflux condenser. This set-up was degassed and flushed with argon and 10 mL of anhydrous ether was added to the flask via syringe. The bromide 3 (26.5 g, 80.47 mmol) was dissolved in anhydrous ether (50 mL) and added to the addition funnel. About 5 mL of this ether solution was added to the Mg turnings while stirring vigorously. An exothermic reaction was noticed (to confirm/accelerate the Grignard reagent formation, 5 mg of iodine was added and immediate decolorization was observed confirming the formation of the Grignard reagent) and the ether started refluxing. The rest of the solution of the bromide was added dropwise while keeping the reaction under gentle reflux by cooling the flask in water. After the completion of the addition the reaction mixture was kept at 35 C. for 1 h and then cooled in ice bath. Ethyl formate (2.68 g, 36.2 mmol) was dissolved in anhydrous ether (40 mL) and transferred to the addition funnel and added dropwise to the reaction mixture with stirring. An exothermic reaction was observed and the reaction mixture started refluxing. After the initiation of the reaction the rest of the ethereal solution of formate was quickly added as a stream and the reaction mixture was stirred for a further period of 1 h at ambient temperature. The reaction was quenched by adding 10 mL of acetone dropwise followed by ice cold water (60 mL). The reaction mixture was treated with aq. H2SO4 (10% by volume, 300 mL) until the solution became homogeneous and the layers were separated. The aq. phase was extracted with ether (2×100 mL). The combined ether layers were dried (Na2SO4) and concentrated to get the crude product which was purified by column (silica gel, 0-10% ether in hexanes) chromatography. The slightly less polar fractions were concentrated to get the formate 6a (1.9 g) and the pure product fractions were evaporated to provide the pure product 6b as a colorless oil (14.6 g, 78%).
40%; 8% [0157] The intermediate compounds (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31- tetraen-19-yl formate (6) and (6Z,9Z,28Z,3 lZ)-heptatriaconta-6,9,28,3 l-tetraen-19-ol respectively identified as compounds (6) and (7) in Reaction 2 above were prepared in an oven dried 3-neck 500mL flask that was charged with Mg (0.5g, 20.83mmol, 1.37 eq.) and (one crystal) under argon. The flask was degassed on a high-vacuum line, then flushed with argon (the process was repeated four times) and then stirred at room temperature for approximately 5 minutes. Anhydrous ether (22mL) was added to this flask and the slurry stirred for approximately 10 minutes. Next, 5g (15.2mmol, 1 eq.) of compound (5) (<strong>[4102-60-7]linoleyl bromide</strong>) was added under argon (color change was observed after the addition of approximately 4.5mL of compound (5)) and the reaction stirred at room temperature. An exothermic reaction was observed after stirring for approximately 5 minutes at room temperature. Thus, the mixture was cooled using an ice-water bath for approximately 2 minutes, then the ice-bath was removed and the reaction mixture stirred at room temperature for 2 hours, resulting in an ash colored reaction mixture and not all of the Mg was consumed. The mixture was cooled to 0 C and the HC02Et (0.58 mL, 7.17mmol, 0.47 eq.) was added dropwise directly into the solution. After stirring at room temperature for 3 hours (product was observed after 1 hour by MS and TLC) the mixture was decanted and the Mg turnings washed with ether. The combined washings were diluted with ether (lOOmL), washed with 10% H2S04 (2 X 50mL), water, brine and then dried ( a2S04). The solution was filtered, concentrated and the residue purified by silica-gel column chromatography. [0158] 5-7% ether in hexanes eluted the alcohol (compound (7)) from the residue. Yield: 0.34g (8%). Compound 7: NMR (300 MHz, CDC13): delta 5.38-5.31 (m, 8H), 3.58 (br s, 1H), 2.76 (t, J= 6 Hz, 4 H), 2.04 (q, J= 6.8 Hz, 8H), 1.39-1.26 (m, 40H), 0.88 (t, J= 6.8 Hz, 6H). APCI[M+H] 527, 511 (-H20). [0159] 2% ether in hexanes eluted the formate (compound (6)) from the residue. Yield: 1.7g (40%). Compound 6: XH NMR (300 MHz, CDC13): delta 8.08 (s, 1H), 5.42-5.28 (m, 8H), 4.99-4.95 (m, 1H), 2.76 (t, J= 6 Hz, 4 H), 2.04 (q, J= 6.6 Hz, 8H), 1.39-1.26 (m, 40H), 0.88 (t, J= 6.6 Hz, 6H). APCI[M+H] 557.
Synthesis of Dilinoleyl Methanol (III) To a suspension of Mg turnings (0.45g, 18.7 mmol) with one crystal of iodine in 200 ml_ of anhydrous ether under nitrogen was added a solution of <strong>[4102-60-7]linoleyl bromide</strong> (II) in 50 ml_ of anhydrous ether at room temperature. The resulting mixture was refluxed under nitrogen overnight. The mixture was cooled to room temperature. To the cloudy mixture under nitrogen was added dropwise at room temperature a solution of ethyl formate (0.65g, 18.7 mmol) in 30 ml_ of anhydrous ether. Upon addition, the mixture was stirred at room temperature overnight (20 hours). The ether layer was washed with 10% H2SO4 aqueous solution (100 ml_), water (2 x 100 ml_), brine (150 ml_), and then dried over anhydrous Na2SO4. Evaporation of the solvent gave 5.Og of pale oil. Column chromatography on silica gel (230-400 mesh, 300 ml_) with 0- 7% ether gradient in hexanes as eluent afforded two products, dilinoleyl methanol (2.Og, III) and dilinoleylmethyl formate (1.4g, IV). 1 H NMR (400 MHz, CDCI3) for dilinoleylmethyl formate (IV) delta: 8.10 (1 H, s, CHO), 5.27-5.45 (8H, m, 4 x CH=CH), 4.99 (1 H, quintet, OCH), 2.78 (4H, t, 2 x C=C-CH2-C=C), 2.06 (8H, q, 4 x allylic CH2), 1.5-1.6 (4H, m, 2 x CH2), 1.2-1.5 (32H, m), 0.90 (6H, t, 2 x CH3) ppm.
To a suspension of Mg turnings (0.45 g, 18.7 mmol) with one crystal of iodine in 200 mL of anhydrous ether under nitrogen was added a solution of <strong>[4102-60-7]linoleyl bromide</strong> (II) in 50 mL of anhydrous ether at room temperature. The resulting mixture was refluxed under nitrogen overnight. The mixture was cooled to room temperature. To the cloudy mixture under nitrogen was added dropwise at room temperature a solution of ethyl formate (0.65 g, 18.7 mmol) in 30 mL of anhydrous ether. Upon addition, the mixture was stirred at room temperature overnight (20 hours). The ether layer was washed with 10% H2SO4 aqueous solution (100 mL), water (2×100 mL), brine (150 mL), and then dried over anhydrous Na2SO4. Evaporation of the solvent gave 5.0 g of pale oil. Column chromatography on silica gel (230-400 mesh, 300 mL) with 0-7% ether gradient in hexanes as eluent afforded two products, dilinoleyl methanol (2.0 g, III) and dilinoleylmethyl formate (1.4 g, IV). 1H NMR (400 MHz, CDCl3) for dilinoleylmethyl formate (IV) : 8.10 (1H, s, CHO), 5.27-5.45 (8H, m, 4×CHCH), 4.99 (1H, quintet, OCH), 2.78 (4H, t, 2×CC-CH2-CC), 2.06 (8H, q, 4×allylic CH2), 1.5-1.6 (4H, m, 2×CH2), 1.2-1.5 (32H, m), 0.90 (6H, t, 2×CH3) ppm
A 250 mL three-neck reactor was purged with dry argon, into which 2.21 g (92 mmol) of activated Mg and 12 mL of anhydrous diethyl ether were added. Product 4 (20 g, 61 mmol) was dissolved in anhydrous diethyl ether (40 mL). Under the protection of argon, 8 mL of the product 4 solution was added to the reactor, together with 0.2 mL (2.8 mmol) of dibromomethane. Using a water bath, the temperature of the reaction mixture was increased to 40 C. After the start of the reaction, the heating resource was removed, and the remaining solution (32 mL) was added drop wise to the reactor within 1 hour, while maintaining a gentle reflux of the mixture. After the completion of the addition, the reaction mixture was heated to keep reflux for 1 hour. After the raw materials were completely consumed, the reaction mixture was cooled to below 10 C. using an ice-bath, in which a diethyl ether solution of ethyl formate (prepared by dissolving 2.2 mL of ethyl formate in 32 mL of diethyl ether) was added slowly. The reaction mixture was warmed to room temperature and incubated for 1 hour under stirring. Then ice-cold water (56 mL) and 10% sulfuric acid solution (prepared by dissolving 27.2 mL of sulfuric acid in 272 of ice-cold water) were added, from which the organic layers were separated. The aqueous layer was extracted with diethyl ether (3×80 mL). The combined organic layers were washed with brine solution (80 ml), dried over sodium sulfate (16 g) and filtered. The organic layer was concentrated and organic solvent was removed with a vacuum pump to obtain a crude product (a mixture of alcohols and formate). This crude product was redissolved in 100 ml of THF. To this a solution of NaOH (prepared by dissolving 7.5 g of NaOH in 150 mL of water) was added and the contents were heated to and incubated at 65 C. for 18 hours. After the completion of the reaction, the reaction mixture was cooled to room temperature and extracted with diethyl ether (3×100 mL) The combined organic layers were washed with brine solution (40 mL), dried over sodium sulfate (40 g) and filtered. The organic layer was concentrated. The thus obtained crude product was purified using a 60-120 mesh silica gel (4% ethyl ether in hexane), to obtain the pure product 6a (11.6 g, 80% yield). 1H-NMR (CDCl3, 400 MHz), delta=5.47-5.24 (m, 8H), 3.70-150 (m, 1H), 2.85-2.66 (m, 4H), 2.12-1.91 (m, 9H), 1.55-1.17 (m, 46H), 0.90-0.80 (m, 6H).
1.4 g; 2 g [0205] To a suspension of Mg turnings (0.45g, 18.7 mmol) with one crystal of iodine in 200 mL of anhydrous etherunder nitrogen was added a solution of <strong>[4102-60-7]linoleyl bromide</strong> (II) in 50 mL of anhydrous ether at room temperature. Theresulting mixture was refluxed under nitrogen overnight. The mixture was cooled to room temperature. To the cloudymixture under nitrogen was added dropwise at room temperature a solution of ethyl formate (0.65g, 18.7 mmol) in 30mL of anhydrous ether. Upon addition, the mixture was stirred at room temperature overnight (20 hours). The ether layerwas washed with 10% H2SO4 aqueous solution (100 mL), water (2 x 100 mL), brine (150 mL), and then dried overanhydrous Na2SO4. Evaporation of the solvent gave 5.0g of pale oil. Column chromatography on silica gel (230-400mesh, 300 mL) with 0-7% ether gradient in hexanes as eluent afforded two products, dilinoleyl methanol (2.0g, III) anddilinoleylmethyl formate (1.4g, IV). 1 H NMR (400 MHz, CDCl3) for dilinoleylmethyl formate (IV) delta: 8.10 (1 H, s, CHO),5.27-5.45 (8H, m, 4 x CH=CH), 4.99 (1 H, quintet, OCH), 2.78 (4H, t, 2 x C=C-CH2-C=C), 2.06 (8H, q, 4 x allylic CH2),1.5-1.6 (4H, m, 2 x CH2), 1.2-1.5 (32H, m), 0.90 (6H, t, 2 x CH3) ppm.
A clean dry 200 L total glass reactor fitted with an argon inlet, a reflux condenser and a thermowell was degassed and purged with argon. The reactor was charged with 277 g (11.3 mol) of active magnesium and then 1.5 L of anhydrous ether. The reactor was again evacuated three times and purged with argon. Bromide 4 (2.5 Kg, 7.6 mol) was dissolved in 5 L of anhydrous ether under argon, 1 L of this solution was added to the reactor and then 25 mL (0.35 mol) of dibromomethane was added. The contents of the reactor were heated to 40 C. using a water bath (refluxing after foaming was observed, indicating the onset of Grignard reagent production). After initiating the reaction, the heating apparatus was removed from the reactor and the remaining 4 L of bromide was slowly added over a period of 2 hours 30 minutes while maintaining a gentle reflux of the mixture. After addition was complete, the reaction mixture was again heated to reflux (bath temperature 45 C.) for 1 hour, after which an aliquot of the reaction mixture was quenched with water and analyzed by TLC (hexane, PMA staining). This indicated complete disappearance of the starting bromide. The reaction mixture was cooled to below 10 C. using an ice bath and ethyl formateEther solution (275 mL in 4 L of ether) was added over 2 h 30 min and after addition was complete the reaction mixture was warmed to room temperature and stirred for 1 h. The reaction mixture was cooled to 10 C., acetone (1.15 L) was slowly added to the mixture and then prepared by dissolving 7 L of ice cold water and 3.4 L of sulfuric acid with 34 L of ice cold water ) 10% sulfuric acid solution were added. The product was extracted with 3 × 10 L of ether and the combined organic layers were washed with 10 L of brine and dried over sodium sulfate (2 Kg). Concentration of the organic layer under reduced pressure gave the crude product (2 Kg) as a mixture of required dilinoleyl alcohols along with traces of O-formylated product. This crude product was redissolved in THF (4 L) and loaded into a 20 L glass reactor. To this was added a NaOH solution (0.934 Kg dissolved in 8 L of ice cold water) and the contents were heated at 65 C. for 18 h and then subjected to O-formylation by TLC (10% ether in hexane) Indicating that the product was completely converted to the desired dilinoleyl methanol. The reaction mixture was cooled, extracted with ether (3 × 4 L) and the combined organic layers were washed withWashed with 5 L of brine and dried over sodium sulfate (4 Kg). After filtration, the organic layer was concentrated to give a crude product. The crude product thus obtained was purified by column chromatography using silica gel of 60-120 mesh with 4% ether in hexane. Concentration of the pure product fractions gave pure 6 (1.45 Kg, 80%) as a colorless liquid
In a three-necked flask, 2.21 g of Mg and 12 ml of anhydrous ether were added. The reactor was filled with argon. 20g of product 4 dissolved in40 ml of anhydrous ether. Under argon protection, 8 ml of this solution was added dropwise to the reactor and 0.2 ml of dibromomethane was further added. The reaction solution was heated to 40C in a water bath. After the start of the reaction, the heat source was removed and the remaining 32 ml of solution was added dropwise to the reactor.The composition maintains a slight reflux condition. After completion of the addition, the reaction was heated to maintain reflux. After the reaction is completed,Reaction solutionIce bath cooling below 10C and ethyl formate in diethyl ether (2.2 ml in 32 ml diethyl ether) was added slowly. After addingAfterwards, the reaction was overnight at room temperature. Then 56 ml of ice water and 10% sulfuric acid solution were added, the organic phase was separated and the aqueous phase was extracted with ether.The organic phases are combined, washed with brine and dried over sodium sulfate. Filter and concentrate the organic phase to remove the organic solvent to obtain the crude product (alcohol and AAcid ester mixture) 16g. The crude product was dissolved with 100 ml THF, NaOH solution (7.5 g dissolved in 150 ml water) was added and heated to 65C.The reaction was 18 hours. After the reaction was completed, the reaction was cooled to room temperature and extracted with ether. The organic phases were combined and washed with 40 ml of brine.Di. Dry over sodium sulfate. Filter and concentrate the organic phase. The crude product was purified with 60-120 mesh silica gel (4% ether/n-hexane) to give pure product.DLM6a (11.6 g) (yield 40%).
2.21 g of Mg and 12 ml of anhydrous diethyl ether were added to the three-necked flask. The reactor was filled with argon. 20 g of product 4 was dissolved in 40 ml of anhydrous diethyl ether. Under argon protection, 8 ml of this solution was added dropwise to the reactor, and 0.2 ml of dibromomethane was continuously added. The reaction solution was warmed to 40 C in a water bath. After the reaction started, the heat source was removed, and the remaining 32 ml of the solution was added dropwise to the reactor, and the mixture was kept under a slight reflux. After the completion of the dropwise addition, the mixture was heated to maintain a reflux state. After completion of the reaction, the reaction solution was cooled to 10 C or less with an ice bath, and then a solution of ethyl formate in diethyl ether (2.2 ml in 32 ml of diethyl ether) was slowly added. After the completion of the dropwise addition, the reaction was allowed to proceed overnight at room temperature. Then, 56 ml of ice water and a 10% sulfuric acid solution were added, the organic phase was separated, and the aqueous phase was extracted with diethyl ether. The organic phases were combined, washed with brine and dried over sodium sulfate. Filtration and concentration of the organic phase to remove the organic solvent to obtain a crude product of 16 g (Alcohol and formate mixture). The crude product was dissolved in 100 ml of THF, NaOH solution (7.5 g dissolved in 150 ml of water) was added, and the mixture was heated to 65 C for 18 hours. After the reaction was completed, the reaction was cooled to room temperature, then it was extracted with diethyl ether and the organic phases were combined and washed with 40 ml brine. Dried over sodium sulfate. Filtrated and concentrated the organic phase. The crude product was purified with 60-120 mesh silica gel (4% diethyl ether / n-hexane) to give purified product DLM6a (11.6 g) (yield 40%).

  • 2
  • [ 4102-60-7 ]
  • [ 109-94-4 ]
  • [ 1169768-28-8 ]
YieldReaction ConditionsOperation in experiment
86% To a flame dried 500 mL RB flask, freshly activated 16 Mg turnings (2.4 g, 100 mmol) were added and the flask was equipped with a magnetic stir bar, an addition funnel and a reflux condenser. This set-up was degassed and flushed with argon and 10 mL of anhydrous ether was added to the flask via syringe. The bromide (13 3) (26.5 g, 80.47 mmol) was dissolved in anhydrous ether (50 mL) and added to the addition funnel. About 5 mL of this ether solution was added to the Mg turnings while stirring vigorously. An exothermic reaction was noticed (to confirm/accelerate the Grignard reagent formation, 5 mg of 17 iodine was added and immediate decolorization was observed confirming the formation of the Grignard reagent) and the ether started refluxing. The rest of the solution of the bromide was added dropwise while keeping the reaction under gentle reflux by cooling the flask in 12 water. After the completion of the addition the reaction mixture was kept at 35 C. for 1 h and then cooled in ice bath. 18 Ethyl formate (2.68 g, 36.2 mmol) was dissolved in anhydrous ether (40 mL) and transferred to the addition funnel and added dropwise to the reaction mixture with stirring. An exothermic reaction was observed and the reaction mixture started refluxing. After the initiation of the reaction the rest of the ethereal solution of formate was quickly added as a stream and the reaction mixture was stirred for a further period of 1 h at ambient temperature. The reaction was quenched by adding 10 mL of 19 acetone dropwise followed by ice cold water (60 mL). The reaction mixture was treated with aq. H2SO4 (10% by volume, 300 mL) until the solution became homogeneous and the layers were separated. The aq. phase was extracted with ether (2×100 mL). The combined ether layers were dried (Na2SO4) and concentration of the organic layer over reduced pressure provided the crude product as a mixture of required dilinoleylmethanol along with minor amounts of O-formylated product. This crude product was re-dissolved in 20 THF (100 mL) and treated with ice-cold 21 aqueous NaOH (10%) and heated at 40 C. for 18 h after which the TLC (10% ether in hexanes) showed the complete conversion of the O-formylated product to the required dilinoleylmethanol. The reaction mixture was cooled and was extracted with ether (3×100 mL) and the combined organic layers were washed with brine and dried over sodium sulfate. Filtration followed by concentration of the organic layer provided the crude product. The thus obtained crude product was purified by column chromatography using 60-120 mesh silica gel using 4% ether in hexanes. Concentration of the pure product fractions provided the pure 22 product (15.4 g, 86%) as a colorless liquid. NMR (400 MHz, CDCl3) delta 5.47-5.24 (m, 8H), 3.56 (dd, J=6.8, 4.2, 1H), 2.85-2.66 (m, 4H), 2.12-1.91 (m, 9H), 1.50-1.17 (m, 46H), 0.98-0.76 (m, 6H). 13C NMR (101 MHz, CDCl3) delta 130.41, 130.37, 128.18, 128.15, 77.54, 77.22, 76.91, 72.25, 37.73, 31.75, 29.94, 29.89, 29.83, 29.73, 29.58, 29.53, 27.46, 27.43, 25.89, 25.86, 22.80, 14.30.
81% General procedure: Step 2: A 1 liter RBF was charged with magnesium turnings (11.1 g, 463 mmol), anhydrous THF (65 mL) and stir-bar and flushed with nitrogen. In a separate flask, a solution of <strong>[4102-60-7]linoleyl bromide</strong> (140 g, 425 mL) in anhydrous THF (150 mL) was prepared, and 20 mL of this solution added to the magnesium. When most of the heat had dissipated, the remainder of the bromide was added over a period of 15 minutes. Temperature was then maintained at 45 C. for 4 h. The reaction was then cooled (0 C.). Using a dropping funnel, a solution of ethyl formate (32.4 g, 438 mmol) in anhydrous THF (150 mL) was added over a 40 minute period. The reaction was stirred overnight at room temperature. The reaction was cooled to -15 C. and 5N HCl (185 mL) added slowly. The mixture was transferred to a 2 L separating funnel separated. Water (150 mL) and hexane (150 mL) were added, the mixture washed, and again the aqueous removed. The organic was washed a final time with water (150 mL) and then concentrated to a yellow oil. The yellow oil was stirred with a mixture of EtOH (210 mL), water (30 mL) and KOH (15.8 g) for 1.5 h at room temp. The EtOH was evaporated and the residue treated with hexane (50 mL). 5N HCl (200 mL) was added via dropping funnel. The organic was washed with water (2×50 mL) evaporated, dried and purified by chromatography (0-5% EtOAc in hexane, 91 g, 81%).
81% STEP 2: Al liter REF was charged with magnesium turnings (11.1 g, 463 mmol), anhydrous THF (65 mE) and stir-bar and flushed with nitrogen. In a separate flask, a solution of <strong>[4102-60-7]linoleyl bromide</strong> (140 g, 425 mE) in anhydrous THF (150 mE) was prepared, and 20 mE of this solution added to the magnesium. When most of the heat had dissipated, the remainder of the bromide was added over a period of 15 minutes. Temperature was then maintained at 45 C. for 4 h. The reaction was then cooled (0 C.). Using a dropping thnnd, a solution of ethyl formate (32.4 g, 438 mmol) in anhydrous THF (150 mE) was added over a 40 minute period. The reaction was stirred overnight at room temperature. The reaction was cooled to -15 C. and SN HC1 (185 mE) added slowly. The mixture was transferred to a 2 E separating thnnel separated. Water (150 mE) and hexane (150 mE) were added, the mixture washed, and again the aqueous removed. The organic was washed a final time with water (150 mE) and then concentrated to a yellow oil. The yellow oil was stirred with a mixture of EtOR (210 mE), water (30 mE) and KOR (15.8 g) for 1.5 h at room temp. The EtOR was evaporated and the residue treated with hexane (50 mE). SN HC1 (200 mE) was added via dropping funnel. The organic was washed with water (2x50 mE) evaporated, dried and purified by chromatography (0-5% EtOAc in hexane, 91 g, 81%).
80% A clean dry 200 L total glass reactor fitted with an argon inlet, a reflux condenser and a thermowell was degassed and purged with argon. The reactor was charged with 277 g (11.3 mol) of active magnesium and then 1.5 L of anhydrous ether. The reactor was again evacuated three times and purged with argon. Bromide 4 (2.5 Kg, 7.6 mol) was dissolved in 5 L of anhydrous ether under argon, 1 L of this solution was added to the reactor and then 25 mL (0.35 mol) of dibromomethane was added. The contents of the reactor were heated to 40 C. using a water bath (refluxing after foaming was observed, indicating the onset of Grignard reagent production). After initiating the reaction, the heating apparatus was removed from the reactor and the remaining 4 L of bromide was slowly added over a period of 2 hours 30 minutes while maintaining a gentle reflux of the mixture. After addition was complete, the reaction mixture was again heated to reflux (bath temperature 45 C.) for 1 hour, after which an aliquot of the reaction mixture was quenched with water and analyzed by TLC (hexane, PMA staining). This indicated complete disappearance of the starting bromide. The reaction mixture was cooled to below 10 C. using an ice bath and ethyl formateEther solution (275 mL in 4 L of ether) was added over 2 h 30 min and after addition was complete the reaction mixture was warmed to room temperature and stirred for 1 h. The reaction mixture was cooled to 10 C., acetone (1.15 L) was slowly added to the mixture and then prepared by dissolving 7 L of ice cold water and 3.4 L of sulfuric acid with 34 L of ice cold water ) 10% sulfuric acid solution were added. The product was extracted with 3 × 10 L of ether and the combined organic layers were washed with 10 L of brine and dried over sodium sulfate (2 Kg). Concentration of the organic layer under reduced pressure gave the crude product (2 Kg) as a mixture of required dilinoleyl alcohols along with traces of O-formylated product. This crude product was redissolved in THF (4 L) and loaded into a 20 L glass reactor. To this was added a NaOH solution (0.934 Kg dissolved in 8 L of ice cold water) and the contents were heated at 65 C. for 18 h and then subjected to O-formylation by TLC (10% ether in hexane) Indicating that the product was completely converted to the desired dilinoleyl methanol. The reaction mixture was cooled, extracted with ether (3 × 4 L) and the combined organic layers were washed withWashed with 5 L of brine and dried over sodium sulfate (4 Kg). After filtration, the organic layer was concentrated to give a crude product. The crude product thus obtained was purified by column chromatography using silica gel of 60-120 mesh with 4% ether in hexane. Concentration of the pure product fractions gave pure 6 (1.45 Kg, 80%) as a colorless liquid
71.3% To a suspension of Mg (0.897 g, 36.9 mmol) and ether (20 mL) in RB flask was added <strong>[4102-60-7]linoleyl bromide</strong> (10.0 g, 30.4 mmol) in ether (25 mL) dropwise while keeping the reaction under gentle reflux by cooling the RB flask in water. The reaction mixture was stirred at 35 C for 1 hour. To the above reaction mixture at 0 C was added ethyl formate (1.013 g, 13.68 mmol) in ether (30 mL) dropwise for 10 minutes and the reaction mixture was stirred at room temperature for 1.5 hrs. The reaction mixture was cooled in ice bath, quenched with water (30 mL), treated with 10% H2SO4 (150 mL) until the solution became homogeneous and the layer was separated. The aqueous layer was extracted with ether (200 mL x 2). The solvent was evaporated under reduced pressure to give a residue, which was re-dissolved in THF (50 mL) and 1 N NaOH (30 mL). The reaction mixture was stirred at 40 C for 5 hrs. TLC was used to monitor the reaction progress. If not complete, 1.5 g NaOH was added to the reaction mixture and the reaction mixture was continually stirred at 40 C for overnight. The reaction mixture was extracted with ether (2 x), dried over anhydrous sodium sulfate, and concentrated to give a residue, which was purified by ISCO (120 g gold silica gel cartridge) eluting with hexane to 10% EtOAc in hexane to give dilinoleyl methanol (5.16 g, 9.76 mmol, 71.3 % yield) as a colorless oil. XHNMR (500 MHz, Chloroform-d) 8 5.41-5.30 (m, 8H), 3.58 (s, 1H), 2.77 (t, J= 6.7 Hz, 4H), 2.05 (q, J= 6.9 Hz, 8H), 1.49 - 1.25 (m, 40H), 0.89 (t, J =6.8Hz, 6H).
40% In a three-necked flask, 2.21 g of Mg and 12 ml of anhydrous ether were added. The reactor was filled with argon. 20g of product 4 dissolved in40 ml of anhydrous ether. Under argon protection, 8 ml of this solution was added dropwise to the reactor and 0.2 ml of dibromomethane was further added. The reaction solution was heated to 40C in a water bath. After the start of the reaction, the heat source was removed and the remaining 32 ml of solution was added dropwise to the reactor.The composition maintains a slight reflux condition. After completion of the addition, the reaction was heated to maintain reflux. After the reaction is completed,Reaction solutionIce bath cooling below 10C and ethyl formate in diethyl ether (2.2 ml in 32 ml diethyl ether) was added slowly. After addingAfterwards, the reaction was overnight at room temperature. Then 56 ml of ice water and 10% sulfuric acid solution were added, the organic phase was separated and the aqueous phase was extracted with ether.The organic phases are combined, washed with brine and dried over sodium sulfate. Filter and concentrate the organic phase to remove the organic solvent to obtain the crude product (alcohol and AAcid ester mixture) 16g. The crude product was dissolved with 100 ml THF, NaOH solution (7.5 g dissolved in 150 ml water) was added and heated to 65C.The reaction was 18 hours. After the reaction was completed, the reaction was cooled to room temperature and extracted with ether. The organic phases were combined and washed with 40 ml of brine.Di. Dry over sodium sulfate. Filter and concentrate the organic phase. The crude product was purified with 60-120 mesh silica gel (4% ether/n-hexane) to give pure product.DLM6a (11.6 g) (yield 40%).
In water; Synthesis of Dilinoleyl Methanol (III) To a suspension of Mg turnings (0.45 g, 18.7 mmol) with one crystal of iodine in 200 mL of anhydrous ether under nitrogen was added a solution of <strong>[4102-60-7]linoleyl bromide</strong> (II) in 50 mL of anhydrous ether at room temperature. The resulting mixture was refluxed under nitrogen overnight. The mixture was cooled to room temperature. To the cloudy mixture under nitrogen was added dropwise at room temperature a solution of ethyl formate (0.65 g, 18.7 mmol) in 30 mL of anhydrous ether. Upon addition, the mixture was stirred at room temperature overnight (20 hours). The ether layer was washed with 10% H2SO4 aqueous solution (100 mL), water (2*100 mL), brine (150 mL), and then dried over anhydrous Na2SO4. Evaporation of the solvent gave 5.0 g of pale oil. Column chromatography on silica gel (230-400 mesh, 300 mL) with 0-7% ether gradient in hexanes as eluent afforded two products, dilinoleyl methanol (2.0 g, III) and dilinoleylmethyl formate (1.4 g, IV).
11.6 g 2.21 g of Mg and 12 ml of anhydrous diethyl ether were added to the three-necked flask. The reactor was filled with argon. 20 g of product 4 was dissolved in 40 ml of anhydrous diethyl ether. Under argon protection, 8 ml of this solution was added dropwise to the reactor, and 0.2 ml of dibromomethane was continuously added. The reaction solution was warmed to 40 C in a water bath. After the reaction started, the heat source was removed, and the remaining 32 ml of the solution was added dropwise to the reactor, and the mixture was kept under a slight reflux. After the completion of the dropwise addition, the mixture was heated to maintain a reflux state. After completion of the reaction, the reaction solution was cooled to 10 C or less with an ice bath, and then a solution of ethyl formate in diethyl ether (2.2 ml in 32 ml of diethyl ether) was slowly added. After the completion of the dropwise addition, the reaction was allowed to proceed overnight at room temperature. Then, 56 ml of ice water and a 10% sulfuric acid solution were added, the organic phase was separated, and the aqueous phase was extracted with diethyl ether. The organic phases were combined, washed with brine and dried over sodium sulfate. Filtration and concentration of the organic phase to remove the organic solvent to obtain a crude product of 16 g (Alcohol and formate mixture). The crude product was dissolved in 100 ml of THF, NaOH solution (7.5 g dissolved in 150 ml of water) was added, and the mixture was heated to 65 C for 18 hours. After the reaction was completed, the reaction was cooled to room temperature, then it was extracted with diethyl ether and the organic phases were combined and washed with 40 ml brine. Dried over sodium sulfate. Filtrated and concentrated the organic phase. The crude product was purified with 60-120 mesh silica gel (4% diethyl ether / n-hexane) to give purified product DLM6a (11.6 g) (yield 40%).

  • 3
  • [ 4102-60-7 ]
  • [ 1169768-28-8 ]
YieldReaction ConditionsOperation in experiment
81% A 1 liter RBF was charged with magnesium turnings (11.1 g, 463 mmol), anhydrous THF (65 mL) and stir-bar and flushed with nitrogen. In a separate flask, a solution of <strong>[4102-60-7]linoleyl bromide</strong> (140 g, 425 mL) in anhydrous THF (1 0 mL) was prepared, and 20 mL of this solution added to the magnesium. When most of the heat had dissipated, the remainder of the bromide was added over a period of 15 minutes. Temperature was then maintained at 45C for 4 h. The reaction was then cooled (0C). Using a dropping funnel, a solution of ethyl formate (32.4 g, 438 mmol) in anhydrous THF (150 mL) was added over a 40 minute period. The reaction was stirred overnight at room temperature. The reaction was cooled to -15C and 5N HC1 (185 mL) added slowly. The mixture was transferred to a 2 L separating funnel separated. Water (150 mL) and hexane (150 mL) were added, the mixture washed, and again the aqueous removed. The organic was washed a final time with water (150 mL) and then concentrated to a yellow oil. The yellow oil was stirred with a mixture of EtOH (210 mL), water (30 mL) and KOH (15.8 g) for 1.5 h at room temp. The EtOH was evaporated and the residue treated with hexane (50 mL). 5N HC1 (200 mL) was added via dropping funnel. The organic was washed with water (2 x 50 mL) evaporated, dried and purified by chromatography (0 - 5% EtOAc in hexane, 91 g, 81%).
11.6 g A 250 mL three-neck reactor was purged with dry argon, into which 2.21 g (92 mmol) of activated Mg and 12 mL of anhydrous diethyl ether were added. Product 4 (20 g, 61 mmol) was dissolved in anhydrous diethyl ether (40 mL). Under the protection of argon, 8 mL of the product 4 solution was added to the reactor, together with 0.2 mL (2.8 mmol) of dibromomethane. Using a water bath, the temperature of the reaction mixture was increased to 40 C. After the start of the reaction, the heating resource was removed, and the remaining solution (32 mL) was added drop wise to the reactor within 1 hour, while maintaining a gentle reflux of the mixture. After the completion of the addition, the reaction mixture was heated to keep reflux for 1 hour. After the raw materials were completely consumed, the reaction mixture was cooled to below 10 C. using an ice-bath, in which a diethyl ether solution of ethyl formate (prepared by dissolving 2.2 mL of ethyl formate in 32 mL of diethyl ether) was added slowly. The reaction mixture was warmed to room temperature and incubated for 1 hour under stirring. Then ice-cold water (56 mL) and 10% sulfuric acid solution (prepared by dissolving 27.2 mL of sulfuric acid in 272 of ice-cold water) were added, from which the organic layers were separated. The aqueous layer was extracted with diethyl ether (3×80 mL). The combined organic layers were washed with brine solution (80 ml), dried over sodium sulfate (16 g) and filtered. The organic layer was concentrated and organic solvent was removed with a vacuum pump to obtain a crude product (a mixture of alcohols and formate). This crude product was redissolved in 100 ml of THF. To this a solution of NaOH (prepared by dissolving 7.5 g of NaOH in 150 mL of water) was added and the contents were heated to and incubated at 65 C. for 18 hours. After the completion of the reaction, the reaction mixture was cooled to room temperature and extracted with diethyl ether (3×100 mL) The combined organic layers were washed with brine solution (40 mL), dried over sodium sulfate (40 g) and filtered. The organic layer was concentrated. The thus obtained crude product was purified using a 60-120 mesh silica gel (4% ethyl ether in hexane), to obtain the pure product 6a (11.6 g, 80% yield). 1H-NMR (CDCl3, 400 MHz), delta=5.47-5.24 (m, 8H), 3.70-150 (m, 1H), 2.85-2.66 (m, 4H), 2.12-1.91 (m, 9H), 1.55-1.17 (m, 46H), 0.90-0.80 (m, 6H).
  • 4
  • [ 4102-60-7 ]
  • [ 109-94-4 ]
  • [ 74-95-3 ]
  • [ 1169768-27-7 ]
  • [ 1169768-28-8 ]
YieldReaction ConditionsOperation in experiment
A clean, dry 20 L all glass reactor fitted with argon inlet, reflux condenser and thermowell was degassed and purged with argon. The reactor was charged with 277 g (11.3 mol) of activated magnesium followed by 1.5 L of anhydrous ether. The reactor was again degassed three times and purged with argon. The bromide 4 (2.5 Kg, 7.6 mol) was dissolved in 5 L of anhydrous ether under argon and 1 L of this solution was added to the reactor followed by 25 mL (0.35 mol) of dibromomethane. The contents of the reactor were heated to 40 C. using a water bath (effervescence was observed followed by reflux indicating the initiation of Grignard reagent formation). After the initiation of the reaction, the heating was removed from the reactor and the remaining 4 L of the bromide was slowly added over a period of 2 hr 30 min maintaining a gentle reflux of the mixture. After completion of the addition, the reaction mixture was again heated to reflux (bath temperature 45 C.) for 1 hr after which an aliquot of the reaction mixture was quenched with water and analyzed by TLC (Hexanes, PMA stain) which showed complete consumption of starting bromide. The reaction mixture was cooled below 10 C. using an ice bath and a solution of ethyl formate (275 mL in 4 L of ether) in ether was added over a period of 2 hr 30 min and after completion of the addition the reaction mixture was warmed to room temperature and stirred for 1 hr. The reaction mixture was cooled back to 10 C. and acetone (1:15 L) was added slowly to the mixture followed by the addition of 7 L of ice-cold water and a solution of 10% sulfuric acid (prepared by diluting 3.4 L of sulfuric acid with 34 L of ice-cold water). The product was extracted with 3×10 L of ether and the combined organic layers were washed with 10 L of brine and dried over sodium sulfate (2 Kg). Concentration of the organic layer over reduced pressure provided the crude product (2 Kg) as a mixture of required dilindleyl alcohol along with minor amounts of O-formylated product. This crude product was redissoloved in THF (4 L) and charged into the 20 L glass reactor. To this a solution of NaOH (0.934 Kg dissolved in 8 L of ice-cold water) was added and the contents were heated at 65 C. for 18 h after which the TLC (10% ether in hexanes) showed complete conversion of the O-formylated product to the required dilinoleylmethanol. The reaction mixture was cooled and was extracted with ether (3×4 L) and the combined organic layers were washed with 5 L of brine and dried over sodium sulfate (4 Kg). Filtration followed by concentration of the organic layer provided the crude product. The thus obtained crude product was purified by column chromatography using 60-120 mesh silica gel using 4% ether in hexanes. Concentration of the pure product fractions provided the pure 6 (1.45 Kg, 80%) as a colorless liquid. NMR (400 MHz, CDCl3) delta 5.47-5.24 (m, 8H), 3.56 (dd, J=6.8, 4.2, 1H), 2.85-2.66 (m, 4H), 2.12-1.91 (m, 9H), 1.50-1.17 (m, 46H), 0.98-0.76 (m, 6H). 13C NMR (101 MHz, CDCl3) delta 130.41, 130.37, 128.18, 128.15, 77.54, 77.22, 76.91, 72.25, 37.73, 31.75, 29.94, 29.89, 29.83, 29.73, 29.58, 2953, 27.46, 27.43, 25.89, 25.86, 22.80, 14.30.
  • 5
  • [ 4102-60-7 ]
  • [ 109-94-4 ]
  • [ 74-95-3 ]
  • [ 1169768-28-8 ]
YieldReaction ConditionsOperation in experiment
80% A clean, dry 20 L all glass reactor fitted with argon inlet, reflux condenser and thermowell was degassed and purged with argon. The reactor was charged with 277 g (11.3 mol) of activated magnesium followed by 1.5 L of anhydrous ether. The reactor was again degassed three times and purged with argon. The bromide 4 (2.5 Kg, 7.6 mol) was dissolved in 5 L of anhydrous ether under argon and 1 L of this solution was added to the reactor followed by 25 mL (0.35 mol) of dibromomethane. The contents of the reactor were heated to 40 C. using a water bath (effervescence was observed followed by reflux indicating the initiation of Grignard reagent formation). After the initiation of the reaction, the heating was removed from the reactor and the remaining 4 L of the bromide was slowly added over a period of 2 hr 30 min maintaining a gentle reflux of the mixture. After completion of the addition, the reaction mixture was again heated to reflux (bath temperature 45 C.) for 1 hr after which an aliquot of the reaction mixture was quenched with water and analyzed by TLC (Hexanes, PMA stain) which showed complete consumption of starting bromide. The reaction mixture was cooled below 10 C. using an ice bath and a solution of ethyl formate (275 mL in 4 L of ether) in ether was added over a period of 2 hr 30 min and after completion of the addition the reaction mixture was warmed to room temperature and stirred for 1 hr. The reaction mixture was cooled back to 10 C. and acetone (1:15 L) was added slowly to the mixture followed by the addition of 7 L of ice-cold water and a solution of 10% sulfuric acid (prepared by diluting 3.4 L of sulfuric acid with 34 L of ice-cold water). The product was extracted with 3×10 L of ether and the combined organic layers were washed with 10 L of brine and dried over sodium sulfate (2 Kg). Concentration of the organic layer over reduced pressure provided the crude product (2 Kg) as a mixture of required dilindleyl alcohol along with minor amounts of O-formylated product. This crude product was redissoloved in THF (4 L) and charged into the 20 L glass reactor. To this a solution of NaOH (0.934 Kg dissolved in 8 L of ice-cold water) was added and the contents were heated at 65 C. for 18 h after which the TLC (10% ether in hexanes) showed complete conversion of the O-formylated product to the required dilinoleylmethanol. The reaction mixture was cooled and was extracted with ether (3×4 L) and the combined organic layers were washed with 5 L of brine and dried over sodium sulfate (4 Kg). Filtration followed by concentration of the organic layer provided the crude product. The thus obtained crude product was purified by column chromatography using 60-120 mesh silica gel using 4% ether in hexanes. Concentration of the pure product fractions provided the pure 6 (1.45 Kg, 80%) as a colorless liquid. NMR (400 MHz, CDCl3) delta 5.47-5.24 (m, 8H), 3.56 (dd, J=6.8, 4.2, 1H), 2.85-2.66 (m, 4H), 2.12-1.91 (m, 9H), 1.50-1.17 (m, 46H), 0.98-0.76 (m, 6H). 13C NMR (101 MHz, CDCl3) delta 130.41, 130.37, 128.18, 128.15, 77.54, 77.22, 76.91, 72.25, 37.73, 31.75, 29.94, 29.89, 29.83, 29.73, 29.58, 2953, 27.46, 27.43, 25.89, 25.86, 22.80, 14.30.
 

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