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[ CAS No. 58186-27-9 ] {[proInfo.proName]}

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Chemical Structure| 58186-27-9
Chemical Structure| 58186-27-9
Structure of 58186-27-9 * Storage: {[proInfo.prStorage]}
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Product Details of [ 58186-27-9 ]

CAS No. :58186-27-9 MDL No. :MFCD00274552
Formula : C19H30O5 Boiling Point : -
Linear Structure Formula :- InChI Key :JGPMMRGNQUBGND-UHFFFAOYSA-N
M.W : 338.44 Pubchem ID :3686
Synonyms :
CV-2619;Mnesis;Catena, Raxone, Sovrima

Calculated chemistry of [ 58186-27-9 ]

Physicochemical Properties

Num. heavy atoms : 24
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.68
Num. rotatable bonds : 12
Num. H-bond acceptors : 5.0
Num. H-bond donors : 1.0
Molar Refractivity : 94.12
TPSA : 72.83 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : No
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.3 cm/s

Lipophilicity

Log Po/w (iLOGP) : 3.76
Log Po/w (XLOGP3) : 4.32
Log Po/w (WLOGP) : 3.46
Log Po/w (MLOGP) : 0.85
Log Po/w (SILICOS-IT) : 4.81
Consensus Log Po/w : 3.44

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 1.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.85

Water Solubility

Log S (ESOL) : -3.87
Solubility : 0.0459 mg/ml ; 0.000136 mol/l
Class : Soluble
Log S (Ali) : -5.56
Solubility : 0.000925 mg/ml ; 0.00000273 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -5.35
Solubility : 0.00152 mg/ml ; 0.00000448 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 1.0 alert
Brenk : 1.0 alert
Leadlikeness : 2.0
Synthetic accessibility : 3.9

Safety of [ 58186-27-9 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H332-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 58186-27-9 ]

* 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 [ 58186-27-9 ]

[ 58186-27-9 ] Synthesis Path-Downstream   1~85

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YieldReaction ConditionsOperation in experiment
83% With Jones reagent; In acetone; Preparation of <strong>[58186-27-9]Idebenone</strong> acid: 10-(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dienyl)decanoic acid; Jones Reagent was freshly prepared as follows: CrO3 (12.5 g) diluted with concentrated H2SO4 (12.5 mL) was mixed and carefully added to ice cold water (37.5 mL); the contents were mixed and allowed to warm to room temperature. <strong>[58186-27-9]Idebenone</strong> (2.50 g, 7.39 mmol) was weighed out into a 250 mL round bottom flask containing a stir-bar. Acetone (100 mL) was then added drop-wise and mixed to afford a bright orange solution. While stirring at room temperature, Jones reagent was added and the reaction was monitored via SiO2 TLC. Additional Jones reagent was added until TLC suggested that oxidation was complete (tR shift of 0.50 to 0.62; 1:1 EtOAc:Hexane). The crude material was concentrated under reduced pressure and then purified by SiO2 chromatography. Product only fractions were combined and concentrated under reduced pressure and further dried under a vacuum line to afford 2.15 g of orange solid; 83% yield. 1H NMR (300 MHz; DMSO-d6) delta 11.95 (bs, 1 H; disappears with the addition of D2O), 3.87 (s, 6H; -OMe), 2.41-2.36 (m, 2H), 2.36-2.30 (t, 2H), 1.92 (s, 3H), 1.52-1.46 (m, 2H), 1.31-1.19 (bs, 12H); 13C NMR (75 MHz; DMSO-d6) 184.0, 183.5, 174.5, 144.3, 144.2, 141.9, 138.2, 60.7, 33.7, 29.2, 28.8, 28.7, 28.6, 28.1, 25.7, 24.5, 11.6.
With Jones reagent; In acetone; at 0℃; for 0.333333h; Jones reagent was prepared by dissolving 670 mg of Cr03 in 1.25 ml dist. water. To this solution was added 0.58 ml of cone. H2S04 while cooling in an ice bath. After 5 min, the precipitating salts were brought into solution by dropwise addition of 0.15 ml of water.<strong>[58186-27-9]Idebenone</strong> (508 mg) was dissolved in 20 ml of acetone and cooled to 0 C in an ice bath. The Jones reagent was added dropwise and the mixture was stirred for 20 min at 0 C. The reaction mixture was diluted with 200 ml of water and the suspension was extracted with CH2CI2 (3 x). The combined organic phase was extracted with 0.05 n HCI (2x), dried over MgS04, filtered and evaporated to yield a red oil. This was purified by column chromatography with hexane/EtOAc 5:1. The resulting red oil was dissolved in 3 ml of diethyl ether and precipitated by cooling the solution to -78 C and addition of 3 ml of hexane. The precipitate was collected by filtration and dried in vacuo.
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  • [ 116460-82-3 ]
  • [ 116460-81-2 ]
  • [ 88543-33-3 ]
  • [ 88543-34-4 ]
  • 5
  • [ 58186-27-9 ]
  • [ 89048-27-1 ]
YieldReaction ConditionsOperation in experiment
84% To a solution of oxalyl chloride (1.0 mL, 1 1.82 mmol, 2 eq) in dry dichloromethane (40 mL) cooled to -78C was added over a period of 5 min DMSO (1.68 mL, 23.64 mmol, 4 eq). After 10 min of stirring at this temperature, a solution of idebenone (2.0 g, 5.91 mmol) in CH2C12 (20 mL) was added over a period of 5 min. After another 5 min of stirring, Et3N (6.6 mL, 47.28 mmol, 8 eq) and the reaction stirred for 1 h and then left to warm to rt. Water was added and the organic layer was extracted, washed successively with 0.1 M aqueous HCl, water and brine, dried on sodium sulfate, filtered and evaporated. The residue was purified by flash chromatography (Biotage SP4, SNAP 100 column, EtOAc in Hex from 20% to 40% in 10 CV) to afford the title compound as a yellow solid (1.68 g Yield: 84%). 1H NMR (300 MHz, CDC13) delta 9.76 (d, J = 1.6, 1H), 3.99 (s, 6H), 2.42 (dt, J = 9.0, 4.4, 4H), 2.01 (s, 3H), 1.68 - 1.58 (m, 2H), 1.35- 1.21 (m, 18H).
84% With oxalyl dichloride; triethylamine; In dichloromethane; dimethyl sulfoxide; at -78℃; for 1.5h; Step 1: Synthesis of 10-(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-l,4- dienyl)decanal To a solution of oxalyl chloride (1.0 mL, 1 1.82 mmol, 2 eq) in dry dichloromethane (40 mL) cooled to -78C was added over a period of 5 min DMSO (1.68 mL, 23.64 mmol, 4 eq). After 10 min of stirring at this temperature, a solution of idebenone (2.0 g, 5.91 mmol) in CH2C12 (20 mL) was added over a period of 5 min. After another 5 min of stirring, Et3N (6.6 mL, 47.28 mmol, 8 eq) and the reaction stirred for 1 h and then left to warm to rt. Water was added and the organic layer was extracted, washed successively with 0.1 M aqueous HCl, water and brine, dried on sodium sulfate, filtered and evaporated. The residue was purified by flash chromatography (Biotage SP4, SNAP 100 column, EtOAc in Hex from 20% to 40% in 10 CV) to afford the title compound as a yellow solid (1.68 g Yield: 84%). 1H NM (300 MHz, CDC13) delta 9.76 (d, J= 1.6, 1H), 3.99 (s, 6H), 2.42 (dt, J = 9.0, 4.4, 4H), 2.01 (s, 3H), 1.68 - 1.58 (m, 2H), 1.35-1.21 (m, 18H).
With Dess-Martin periodane; In dichloromethane; at 0℃; for 4h;Inert atmosphere; Under argon atmosphere, idebenone (4 g) was dissolved in dry dichloromethane (100 ml) and the solution was cooled to 0C. Dess Martin reagent (6 g) was added and the reaction mixture was stirred at 0C for 4h. The solution was diluted with dichloromethane (100 ml) and washed with a 1 M aqueous sodium thiosulfate solution (100 ml), saturated sodium bicarbonate solution (100 ml), water (100 ml) and brine (100 ml). The organic layer was dried over sodium sulfate, filtrated, and the solvent was removed under reduced pressure. The crude product was purified by flash-chromatography (AcOEt-cyclohexane).
  • 8
  • [ 58186-28-0 ]
  • [ 58186-27-9 ]
YieldReaction ConditionsOperation in experiment
80% With sodium carbonate In methanol; water at 25℃; for 20h;
61% With water; sodium carbonate In methanol at 0℃; for 36h;
With hydrogenchloride; sodium chloride In methanol 1 Example 1 In a mixture of 0.04 ml of concentrated hydrochloric acid and 11 ml of methanol was dissolved 216 mg of 6-(10-acetoxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone, and the solution was left standing overnight at room temperature. The reaction solution was concentrated under reduced pressure and the concentrate was diluted with water, which was subjected to extraction with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride, then dried. The solvent was evaporated under reduced pressure. The residue was recrystallized from hexane-ethylacetate to yield 115 mg of 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone as orange-colored needles, m.p. 52°-53° C.
  • 9
  • [ 14065-32-8 ]
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  • [ 818-88-2 ]
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  • [ 374622-25-0 ]
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  • 12
  • [ 374622-17-0 ]
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  • 13
  • 10-(2,3,4,5-tetramethoxy-6-methylphenyl)-9-decenylacetate [ No CAS ]
  • [ 58186-27-9 ]
  • 14
  • [ 374622-20-5 ]
  • [ 58186-27-9 ]
  • 15
  • [ 374622-18-1 ]
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  • [ 96012-40-7 ]
  • 18
  • [ 58186-27-9 ]
  • [ 86515-60-8 ]
  • 19
  • [ 58186-27-9 ]
  • Acetic acid 10-(3,4-dimethoxy-2,5-bis-methoxymethoxy-6-methyl-phenyl)-decyl ester [ No CAS ]
  • 20
  • [ 58186-27-9 ]
  • 2-<10-(5,6-dimethoxy-3-methyl-1,4-benzoquinon-2-yl)decyl>3-hydroxytetracosanoic acid [ No CAS ]
  • 21
  • [ 58186-27-9 ]
  • 2-[10-(2,5-Dihydroxy-3,4-dimethoxy-6-methyl-phenyl)-decyl]-3-hydroxy-tetracosanoic acid [ No CAS ]
  • 22
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  • [ 86515-55-1 ]
  • 23
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  • [ 96012-42-9 ]
  • 24
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  • [ 96022-21-8 ]
  • 25
  • [ 58186-27-9 ]
  • 2-[10-(3,4-Dimethoxy-2,5-bis-methoxymethoxy-6-methyl-phenyl)-decyl]-3-oxo-tetracosanoic acid ethyl ester [ No CAS ]
  • 26
  • [ 58185-89-0 ]
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  • 33
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  • [ 99590-15-5 ]
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  • [ 95233-74-2 ]
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  • 43
  • [ 104966-97-4 ]
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  • 44
  • [ 77712-30-2 ]
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  • [ 104966-92-9 ]
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  • 46
  • [ 6946-46-9 ]
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  • 48
  • [ 58185-79-8 ]
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  • 49
  • [ 58186-27-9 ]
  • [ 124-63-0 ]
  • [ 845959-53-7 ]
YieldReaction ConditionsOperation in experiment
91% With dmap; triethylamine; In dichloromethane; at 0 - 20℃; for 16h; To a solution of 2-(10-hydroxydecyl)-5,6-dimethoxy-3-methyl cyclohexa-2,5-diene-l ,4-dione (2.0 g, 5.91 mmol) and triethylamine (0.9 mL, 6.5 mmol, 1.1 eq) in dry CH2C12 (20 mL) was added at 0C a solution of methansulfonyl chloride (505 L, 6.5 mmol, 1.1 eq) in CH2C12 (5 mL) followed by DMAP (10 mg). The reaction was left at room temperature for 16 hrs and then washed successively with water, saturated NaHCO3, water and brine. The residue was purified by column chromatography (SNAP 100, gradient system from 20/80 ethyl acetate/n-hexane to 40/60 ethyl acetate/n- hexane in 10 CV) to give the title compound as an orange solid (2.21 g, 91%). 1H NMR (300 MHz, CDC13) delta 4.22 (t, J = 6.6, 2H), 3.99 (s, 6H), 3.00 (s, 3H), 2.44 (t, J = 7.2, 2H), 2.01 (s, 3H), 1.81 - 1.66 (m, 2H), 1.31 (m, 14H).
91% With dmap; triethylamine; In dichloromethane; at 0 - 20℃; for 16h; Step 1: Synthesis of 10-(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-l,4- dienyl)decyl methane sulfonate A solution of 2-(10-hydroxydecyl)-5,6-dimethoxy-3-methyl cyclohexa-2,5- diene- 1 ,4-dione (2.0 g, 5.91 mmol) and triethylamine (0.9 mL, 6.5 mmol, 1.1 eq) in dry CH2C12 (20 mL) was added at 0C with a solution of methane sulfonyl chloride (505 L, 6.5 mmol, 1.1 eq) in CH2C12 (5mL) followed by DMAP (10 mg). The reaction was left at room temperature for 16 hrs and then washed successively with water, saturated NaHCO3, water and brine. The residue was purified by column chromatography (SNAP 100, gradient system from 20/80 ethyl acetate/n-hexane to 40/60 ethyl acetate/n-hexane in 10 CV) to give the title compound as an orange solid (2.21 g, 91%). 1H NMR (300 MHz, CDC13) delta 4.22 (t, J = 6.6, 2H), 3.99 (s, 6H), 3.00 (s, 3H), 2.44 (t, J = 7.2, 2H), 2.01 (s, 3H), 1.81 - 1.66 (m, 2H), 1.31 (m, 14H).
With triethylamine; In dichloromethane; at 10 - 15℃; for 1.5 - 1.75h; Stage 1 Scheme: Dichloromethane Triethylamine Me0 MeO,'I Mol. : 101. 19 Mezzo O O , OH *"OMs C19H3005 Mol. Wt. : 44 Methanesulfonyl Mol. : 416. 53 CH3SO2C1 Mol. Step: 1. <strong>[58186-27-9]Idebenone</strong> (AL, 0.25 kg, 0.74 mol) is dissolved in 2.5 L of reaction grade DCM, and the mixture is then cooled to 10 I3 C under an inert atmosphere. 2. Triethylamine (0.152 kg, 1.5 mol) is added in one portion at ambient temperature and the mixture allowed to re-equilibrate to 10 I3 C. 3. A solution of methanesulfonyl chloride (0.094 kg, 0.82 mol) in 0.5 L of DCM is then added gradually at such a rate as to maintain an internal temperature OF APPROX. 10-15 C. (ORA THIS SCALE THE ADDITION WAS COMPLETE after 75 minutes). 4. The reaction mixture is agitated for a further 15-30 minutes, 5. IPC checked for completion by TLC (Rf 0.65 5% Ethanol/ Dichloromethane). 6. The mixture is then washed with water (0. 85 L) and saturated aqueous sodium bicarbonate solution (0. 85 L). 7. The organic layer is evaporated to a red liquid under reduced pressure at 40-45 C. After drying for an additional 2-4 hours under high vacuum at ambient temperature, the crude A2 so obtained is used directly in the next step. Yield unknown as solvent was trapped in the liquid.
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  • [ 288-32-4 ]
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  • [ 75-36-5 ]
  • [ 58479-61-1 ]
  • [ 152980-15-9 ]
YieldReaction ConditionsOperation in experiment
With pyridine; sodium dithionite; In dichloromethane; water; EXAMPLE A-7 Sodium 1-O-[2,3-dimethoxy-1-hydroxy-6-(10-hydroxydecyl)-5-methylphenyl]-beta-D-glucopyranosiduronate 2,3-Dimethoxy-6-(10-hydroxydecyl)-5-methyl-1,4-benzoquinone (338 mg, 1 mmol) was dissolved in dichloromethane (5 ml). Pyridine (0.1 ml, 1.2 mmol) followed by acetyl chloride (0.08 ml, 1.1 mmol) was added with stirring under ice-cooling. The mixture was stirred at the same temperature for 1 hour. Water (5 ml) was added to the reaction mixture which was then stirred at room temperature for 20 minutes. Then sodium hydrosulfite (400 mg, 2.3 mmol) was added, and the mixture was stirred for 2 hours. The dichloromethane layer was separated, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in dichloromethane (5 ml), and tert-butylchlorodiphenylsilane (550 mg, 2 mmol) was added. Then imidazole (136 mg, 2 mmol) was added under a stream of nitrogen. The reaction mixture was stirred at 43 C. for 16 hours and then washed with water (5 ml), and the organic layer was dried over anhydrous magnesium sulfate. Concentration under reduced pressure gave crude 6-(10-acetoxydecyl)-4-tert-butyldiphenylsilyloxy-2,3-dimethoxy-5-methylphenol.
With pyridine; sodium dithionite; In dichloromethane; water; REFERENCE EXAMPLE 7 Sodium 2,3-dimethoxy-4-hydroxy-6-(10-hydroxydecyl)-5-methylphenyl-1-sulfate 2,3-Dimethoxy-6-(10-hydroxydecyl)-5-methylbenzoquinone (3.38 g, 10 mmol) was dissolved in dichloromethane (50 ml). Pyridine (1 ml) followed by acetyl chloride (0.8 ml) was added with stirring under ice-cooling, and the mixture was stirred for 1 hour. Water (5 ml) was added to the reaction mixture which was then stirred for 20 minutes. Then sodium hydrosulfite (4 g) was added, and the mixture was stirred at room temperature for 2 hours. The dichloromethane layer was separated, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in dichloromethane (50 ml), and tert-butylchlorodiphenylsilane (5.5 g, 20 mmol) and imidazole (1.36 g, 20 mmol) were added. The mixture was stirred at 43 C. for 16 hours under a stream of nitrogen. The reaction mixture was washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain crude 6-(10-acetoxydecyl)-4-tert-butyldiphenylsilyloxy-2,3-dimethoxy-5-methylphenol. The concentrate was dissolved in dimethylformamide (15 ml).
With pyridine; sodium dithionite; In dichloromethane; water; REFERENCE EXAMPLE 8 Sodium 2,3-dimethoxy-1-hydroxy-6-(10-hydroxydecyl)-5-methylphenyl-4-sulfate 2,3-Dimethoxy-6-(10-hydroxydecyl)-5-methylbenzoquinone (3.38 mg, 10 mmol) was dissolved in dichloromethane (50 ml). Pyridine (1 ml) followed by acetyl chloride (0.8 ml) was added with stirring under ice-cooling. The mixture was stirred for 1 hour. Water (50 ml) was added to the reaction mixture which was then stirred for 20 minutes. Then sodium hydrosulfite (4 g) was added, and the mixture was stirred at room temperature for 2 hours. The dichloromethane layer was separated, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in dichloromethane (50 ml), and tert-butylchlorodiphenylsilane (5.5 g, 20 mmol) and imidazole (1.36 g, 20 mmol) were added. The mixture was stirred at 43 C. for 16 hours under a stream of nitrogen. The reaction mixture was washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain crude 6-(10-acetoxydecyl)-4-tert-butyl diphenylsilyloxy-2,3-dimethoxy-5-methylphenol. The concentrate was dissolved in dichloromethane (100 ml).
  • 51
  • [ 58186-27-9 ]
  • [ 75-36-5 ]
  • [ 58186-28-0 ]
YieldReaction ConditionsOperation in experiment
With pyridine; In dichloromethane; water; REFERENCE EXAMPLE 1 6-(10-Acetoxydecyl)-2,3-dimethoxy-5-methylhydroquinone 2,3-Dimethoxy-6-(10-hydroxydecyl)-5-methyl-1,4-benzoquinone (3.38 g) was dissolved in dichloromethane (50 ml). Pyridine (1 ml) was added, and acetyl chloride (0.8 ml) was added with stirring under ice-cooling. After stirring for 1 hour at the same temperature, the mixture was washed with 0.1N hydrochloric acid (50 ml) followed by water (50 ml). The dichloromethane layer was concentrated under reduced pressure to obtain 6-(10-acetoxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone as a red oil.
  • 52
  • [ 288-32-4 ]
  • [ 58186-27-9 ]
  • [ 58479-61-1 ]
  • [ 152980-15-9 ]
YieldReaction ConditionsOperation in experiment
With pyridine; sodium dithionite; In dichloromethane; water; EXAMPLE A-3 Sodium 1-O-[2,3-dimethoxy-4-hydroxy-6-(10-hydroxydecyl)-5-methylphenyl]-beta-D-glucopyranosiduronate 2,3-Dimethoxy-6-(10-hydroxydecyl)-5-methyl-1,4-benzoquinone (338 mg, 1 mmol) was dissolved in dichloromethane (5 ml). Pyridine (0.1 ml, 1.2 mmol) followed by acetyl chlorides(0.08 ml, 1.1 mmol) was added with stirring under ice-cooling. The mixture was stirred at the same temperature for 1 hour. Water (5 ml) was added to the reaction mixture which was then stirred at room temperature for 20 minutes. Then sodium hydrosulfite (400 mg, 2.3 mmol) was added, and the mixture was stirred for 2 hours. The dichloromethane layer was separated, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in dichloromethane (5 ml), and tert-butylchlorodiphenylsilane (550 mg, 2 mmol) was added. Then imidazole (136 mg, 2 mmol) was added under a stream of nitrogen. After stirring at 43 C. for 16 hours, the mixture was washed with water (5 ml), and the organic layer was dried over anhydrous magnesium sulfate. Concentration under reduced pressure gave crude 6-(10-acetoxydecyl)-4-tert-butyldiphenylsilyloxy-2,3-dimethoxy-5-methylphenol.
  • 53
  • [ 58186-27-9 ]
  • [ 76-83-5 ]
  • 2,3-Dimethoxy-5-methyl-6-(10-trityloxydecyl)hydroquinone [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium dithionite; triethylamine; In dichloromethane; water; REFERENCE EXAMPLE 11 2,3-Dimethoxy-5-methyl-6-(10-trityloxydecyl)hydroquinone 2,3-Dimethoxy-6-(10-hydroxydecyl)-5-methylbenzoquinone (33.8 g) was dissolved in dichloromethane (250 ml). Trityl chloride (30 g) followed by triethylamine (10 g) was added, and the mixture was stirred at room temperature overnight. Then water (250 ml) containing sodium hydrosulfite (40 g) was added, and the mixture was stirred at room temperature for 1 hour. The organic layer was separated, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain the desired compound (80.4 g). NMR (CDCl3) delta (ppm): 1.25 (16H, br.s), 2.15 (3H, s), 2.60 (2H, t, J=7.9Hz), 3.88 (6H, s), 5.25-5.32 (4H, m), 7.21-7.46 (15H, m).
YieldReaction ConditionsOperation in experiment
[spraying powder] idebenone: 20 g sucrose: 20 g corn starch: 25 g L-HPC: 35 g
  • 55
  • disodium nitrosodisulfonate [ No CAS ]
  • [ 77712-29-9 ]
  • [ 58186-27-9 ]
YieldReaction ConditionsOperation in experiment
96.9% In methanol; water; REFERENCE EXAMPLES 4 TO 7 In methanol (5.4 l) was dissolved 10-(2-hydroxy-3,4-dimethoxy-6-methylphenyl)decan-1-ol (271 g), to which was added an aqueous solution of disodium nitrosodisulfonate (6.7 l, content 0.359 mol./l) synthesised by means of electrolytic oxidation. The mixture was stirred for two hours while keeping the temperatures at 50+-2 C. After confirmation of disappearance of the starting material by thin-layer chromatography, water (8.6 l) was added to the reaction mixture, followed by extraction twice with toluene (5.5 and 2.7 l). The toluene layers were combined and washed with water. The toluene layer was concentrated under reduced pressure to obtain a crude product, 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (288 g, content 94.8%, yield 96.9%). This crude product (20 g) was recrystallized from a mixture of toluene (60 ml) and n-hexane (180 ml). The crystals were dissolved in toluene (60 ml), and the solution was allowed to pass through a precoated layer of activated alumina (30 g). The filtrate was concentrated under reduced pressure, and the concentrate was recrystallized again from a mixture of toluene (55 ml) and n-hexane (165 ml). The crystals were further recrystallized from 50% ethanol (108 ml), followed by drying to obtain 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (16.2 g) as orange-yellow crystals, m.p. 54.0 C. Infrared absorption spectrum numaxKBr cm-1: 3550 (OH), 1660, 1650, 1610 (1,4-benzoquinone). Nuclear magnetic resonance spectrum deltappmCDCl3: 1.1 to 1.8 (16 H, multiplet,--(CH2)8 --), 2.00 (3 H, singlet, CH3), 2.43 (2 H, triplet, J=7 Hz, CH2), 3.63 (2 H, triplet, J=6 Hz, CH2 OH), 3.97 (6 H, singlet, OCH3).
  • 56
  • carbon tetrachloride-ethyl acetate [ No CAS ]
  • dichloroethane-ethyl acetate [ No CAS ]
  • [ 58186-27-9 ]
  • [ 89048-27-1 ]
YieldReaction ConditionsOperation in experiment
With sodium acetate; pyridinium chlorochromate; In dichloromethane; REFERENCE EXAMPLE 9 Pyridinium chlorochromate (3.3 g) and sodium acetate (0.5 g) were suspended in dichloromethane (2.5 ml). To the suspension was added a solution of 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (3.38 g) in dichloromethane (20 ml) at room temperature. The mixture was stirred for an hour. Then, additional amount of pyridinium chlorochromate (1 g) and sodium acetate (0.5 g) were added and the mixture was stirred for another 1.5 hours. The reaction mixture was poured into an ice water and the mixture was extracted with ethyl acetate. The extract was treated in a conventional manner and the residue obtained was purified by column chromatography using silica gel. Elution was carried out with dichloroethane-ethyl acetate (9:1) and then with carbon tetrachloride-ethyl acetate (9:1), and the elude was recrystallized from ethyl acetate-hexane to give 6-(9-formylnonyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (1.3 g), melting at 44.5-46.5 C. Elemental analysis: Calcd. for C19 H28 O5: C, 67.83; H, 8.39. Found: C, 67.73; H, 8.27.
YieldReaction ConditionsOperation in experiment
The product was treated with ferric chloride in the same manner as Example 53 and then crystallized from ligroin. The procedure provided 2,3-dimethoxy-5-methyl-6-(10'-hydroxydecyl)-1,4-benzoquinone (formula IV-2 wherein R=H3 CO, n=8, in the free form) (0.65 part) as orange needles melting at 46-50 C. Elemental analysis, C19 H30 O5 -- Calculated: C, 67.43; H, 8.94. Found: C, 67.41; H, 8.94.
850 mg (96%) Example 2 Preparation of Idebenone Conjugated Linoleate (1b)(EX00011-037) Idebenone (2a; 499 mg; 1.48 mmol) was dissolved in 10 mL of toluene. Conjugated linoleic acid (Tonalin FFA; 2.07 g; 5 equiv) was added followed by 500 mg of 4A molecular sieves and 300 mg of Novozym 435. The reaction mixture was stirred at ambient temperature for 2 days, at which point tlc analysis (1:1 ethyl acetate:heptane eluant) indicated a small amount of idebenone. Additional 4A molecular sieves were added and the mixture was stirred for an additional 2 days, at which point tlc analysis indicated no remaining idebenone. The solids were removed by filtration and the precipitate washed with toluene. The combined filtrate and washes were concentrated at reduced pressure. The residue was dissolved in heptane (50 mL) and washed twice with a 1:1 mixture of methanol and 10% aqueous potassium carbonate (50 mL, then 20 mL). The organic layer was further washed with a mixture of 15 mL of methanol, 5 mL of saturated sodium bicarbonate, and 10 mL of water. The organic layer was then dried with sodium sulfate and concentrated to afford 850 mg (96%) of 1b. 1H NMR (CDCl3) delta6.33-6.24 (m,1H); 5.935 (t,1H, J=11.0 Hz); 5.60-5.60 (m,1H); 5.35-5.26 (m,1H); 4.049 (t, 2H, J=6.60 Hz); 3.988 (s, 3H); 3.986 (s, 3H); 2.445 (t, 2H, J=6.87 Hz); 2.285 (t, 2H, J=7.42 Hz); 2.18-2.05 (m, 3H); 2.009 (s, 3H); 1.62-1.56 (m, 5H); 1.30-1.23 (m, 30H); 0.91-0.86 (m, 3H).
850 mg (96%) EXAMPLE 2 Preparation of Idebenone Conjugated Linoleate (1b)(EX0001 1-037) Idebenone (2a; 499 mg; 1.48 mmol) was dissolved in 10 mL of toluene. Conjugated linoleic acid (Tonalin FFA; 2.07 g; 5 equiv) was added followed by 500 mg of 4 A molecular sieves and 300 mg of Novozym 435. The reaction mixture was stirred at ambient temperature for 2 days, at which point tic analysis (1:1 ethyl acetate:heptane eluant) indicated a small amount of idebenone. Additional 4 A molecular sieves were added and the mixture was stirred for an additional 2 days, at which point tic analysis indicated no remaining idebenone. The solids were removed by filtration and the precipitate washed with toluene. The combined filtrate and washes were concentrated at reduced pressure. The residue was dissolved in heptane (50 mL) and washed twice with a 1:1 mixture of methanol and 10% aqueous potassium carbonate (50 mL, then 20 mL). The organic layer was further washed with a mixture of 15 mL of methanol, 5 mL of saturated sodium bicarbonate, and 10 mL of water. The organic layer was then dried with sodium sulfate and concentrated to afford 850 mg (96%) of 1b. 1H NMR (CDCl3) delta 6.33-6.24 (m,1H); 5.935 (t,1H, J=11.0 Hz); 5.60-5.60 (m, 1H); 5.35-5.26 (m, 1H); 4.049 (t, 2H, J=6.60 Hz); 3.988 (s, 3H); 3.986 (s, 3H); 2.445 (t, 2H, J=6.87 Hz); 2.285 (t, 2H, J=7.42 Hz); 2.18-2.05 (m, 3H); 2.009 (s, 3H); 1.62-1.56 (m, 5H); 1.30-1.23 (m, 30H); 0.91-0.86 (m, 3H).
  • 58
  • [ 58186-27-9 ]
  • [ 58186-28-0 ]
YieldReaction ConditionsOperation in experiment
With acetic anhydride; In pyridine; EXAMPLE 55 To a cooled, well stirred solution of 2,3-dimethoxy-5-methyl-6-(10'-hydroxydecyl)-1,4-benzoquinone (formula IV-2 wherein R=H3 CO, n=8, in the free form) (0.3 part) in pyridine (1 volume part) was added acetic anhydride (0.1 volume part). After stirring at room temperature for 1 hour, the mixture was diluted with water, and the aqueous solution was extracted with diethyl ether. The extract was washed successively with water, dilute hydrochloric acid, water, saturated aqueous sodium hydrogen carbonate and water, and dried over anhydrous sodium sulfate. The residue upon removal of the solvent was crystallized from aqueous ethanol to give 2,3-dimethoxy-5-methyl-6-(10'-acetoxydecyl)-1,4-benzoquinone (formula IV-2 wherein R=H3 CO, n=8, in the form of acetate) (0.31 part) as orange needles melting at 38 C. Elemental analysis, C21 H32 O6 -- Calculated: C, 66.30; H, 8.48. Found: C, 66.12; H, 8.59.
  • 59
  • [ 58186-27-9 ]
  • [ 319906-76-8 ]
YieldReaction ConditionsOperation in experiment
idebenone was reacted with pyridine-S03 and the reaction was then stopped using 1 N hydrochloric acid. After shaking out the organic phase using ethyl acetate, the organic phase was dried and concentrated under vacuum. The residue was dissolved in water and insoluble products centrifuged off.
  • 60
  • [ 124-07-2 ]
  • [ 58186-27-9 ]
  • [ 1177393-72-4 ]
YieldReaction ConditionsOperation in experiment
92% With novozym 435; In toluene; at 20℃; for 48h;4A molecular sieves; Example 4: Preparation of ldebenone octanoate (1d)(EX00011-037) ldebenone (2a; 500 mg; 1.48 mmol) was dissolved in 10 mL of toluene. Octanoic acid ( 1.07 g; 5 equiv) was added followed by 500 mg of 4A molecular sieves and 300 mg of Novozym 435. The reaction mixture was stirred at ambient temperature for 2 days, at which point tic analysis (1 :1 ethyl acetate:heptane eluant) indicated no idebenone. The solids were removed by filtration and the precipitate washed with toluene. The combined filtrate and washes were concentrated at reduced pressure. Concentration in vacuo afforded 630 mg (92%) of 1d. 1H NMR (CDCI3) delta 4.051 (t, 2H, J = 6.87 Hz); 3.990 (s, 3H); 3.987 (s, 3H); 2.446 (t, 2H, J = 7.15 Hz); 2.289 (t, 2H1 J = 7.42 Hz); 2.010 (s, 3H); 1.61-1.57 (m, 5H); 1.33-1.28 (m, 30H); 0.878 (t, 3H1 J = 6.60 Hz).
630 mg (92%) In ethyl acetate; toluene; Example 4 Preparation of <strong>[58186-27-9]Idebenone</strong> octanoate (1d)(EX00011-037) <strong>[58186-27-9]Idebenone</strong> (2a; 500 mg; 1.48 mmol) was dissolved in 10 mL of toluene. Octanoic acid (1.07 g; 5 equiv) was added followed by 500 mg of 4A molecular sieves and 300 mg of Novozym 435. The reaction mixture was stirred at ambient temperature for 2 days, at which point tlc analysis (1:1 ethyl acetate:heptane eluant) indicated no idebenone. The solids were removed by filtration and the precipitate washed with toluene. The combined filtrate and washes were concentrated at reduced pressure. Concentration in vacuo afforded 630 mg (92%) of 1d. 1H NMR (CDCl3) delta4.051 (t, 2H, J=6.87 Hz); 3.990 (s, 3H); 3.987 (s, 3H); 2.446 (t, 2H, J=7.15 Hz); 2.289 (t, 2H, J=7.42 Hz); 2.010 (s, 3H); 1.61-1.57 (m, 5H); 1.33-1.28 (m, 30H); 0.878 (t, 3H, J=6.60 Hz).
630 mg (92%) silica gel; In ethyl acetate; toluene; EXAMPLE 4 Preparation of <strong>[58186-27-9]Idebenone</strong> Octanoate (1d)(EX0001 1-037) <strong>[58186-27-9]Idebenone</strong> (2a; 500 mg; 1.48 mmol) was dissolved in 10 mL of toluene. Octanoic acid (1.07 g; 5 equiv) was added followed by 500 mg of 4 A molecular sieves and 300 mg of Novozym 435. The reaction mixture was stirred at ambient temperature for 2 days, at which point tlc analysis (1:1 ethyl acetate:heptane eluant) indicated no idebenone. The solids were removed by filtration and the precipitate washed with toluene. The combined filtrate and washes were concentrated at reduced pressure. Concentration in vacuo afforded 630 mg (92%) of 1d. 1H NMR (CDCl3) delta 4.051 (t, 2H, J=6.87 Hz); 3.990 (s, 3H); 3.987 (s, 3H); 2.446 (t, 2H, J=7.15 Hz); 2.289 (t, 2H, J=7.42 Hz); 2.010 (s, 3H); 1.61-1.57 (m, 5H); 1.33-1.28 (m, 30H); 0.878 (t, 3H, J=6.60 Hz).
  • 61
  • aqueous potassium carbonate [ No CAS ]
  • [ 60-33-3 ]
  • [ 58186-27-9 ]
  • [ 1177393-70-2 ]
YieldReaction ConditionsOperation in experiment
0.84 g (87%) In methanol; n-heptane; water; ethyl acetate; toluene; Example 1 Preparation of <strong>[58186-27-9]Idebenone</strong> Linoleate (1a)(EX00011-037) <strong>[58186-27-9]Idebenone</strong> (2a, R=R1=Me, n=9; 547 mg; 1.6 mmol) was dissolved in 10 mL of toluene. Linoleic acid (2.18 g; 4.9 equiv) was added followed by 641 mg of 4A molecular sieves and 309 mg of Novozym 435. The reaction mixture was stirred at ambient temperature for 2 days, at which point tlc analysis (1:1 ethyl acetate:heptane eluant) indicated no remaining idebenone. The solids were removed by filtration and the precipitate washed with toluene. The combined filtrate and washes were concentrated at reduced pressure. The residue was dissolved in heptane (22 mL) and washed with a mixture of 11 mL of methanol and 11 mL of 10% aqueous potassium carbonate. The organic layer was further washed with a mixture of 11 mL of methanol, 4 mL of saturated sodium bicarbonate, and 7 mL of water. The organic layer was then dried with sodium sulfate and concentrated to afford 0.84 g (87%) of 1a (R=R1=Me, n=9). 1H NMR (CDCl3) delta5.40-5.30 (m, 4H); 4.049 (t, 2H, J=6.87 Hz); 3.988 (s, 6H); 2.768 (t, 2H, J=5.77 Hz); 2.45 (m, 2H); 2.288 (t, 2H, J=7.42 Hz); 2.08-2.01 (m, 3H); 2.009 (s, 3H); 1.64-1.57 (m, 3H); 1.40-1.29 (m, 30H); 0.89 (t, 3H, J=6.60 Hz).
0.84 g (87%) silica gel; In methanol; n-heptane; water; ethyl acetate; toluene; EXAMPLE 1 Preparation of <strong>[58186-27-9]Idebenone</strong> Linoleate (1a)(EX00011-037) <strong>[58186-27-9]Idebenone</strong> (2a, R=R1=Me, n=9; 547 mg; 1.6 mmol) was dissolved in 10 mL of toluene. Linoleic acid (2.18 g; 4.9 equiv) was added followed by 641 mg of 4 A molecular sieves and 309 mg of Novozym 435. The reaction mixture was stirred at ambient temperature for 2 days, at which point tlc analysis (1:1 ethyl acetate:heptane eluant) indicated no remaining idebenone. The solids were removed by filtration and the precipitate washed with toluene. The combined filtrate and washes were concentrated at reduced pressure. The residue was dissolved in heptane (22 mL) and washed with a mixture of 11 mL of methanol and 11 mL of 10% aqueous potassium carbonate. The organic layer was further washed with a mixture of 11 mL of methanol, 4 mL of saturated sodium bicarbonate, and 7 mL of water. The organic layer was then dried with sodium sulfate and concentrated to afford 0.84 g (87%) of 1a (R=R1=Me, n=9). 1H NMR (CDCl3) delta 5.40-5.30 (m, 4H); 4.049 (t, 2H, J =6.87 Hz); 3.988 (s, 6H); 2.768 (t, 2H, J=5.77 Hz); 2.45 (m, 2H); 2.288 (t, 2H, J=7.42 Hz); 2.08-2.01 (m, 3H); 2.009 (s, 3H); 1.64-1.57 (m, 3H); 1.40-1.29 (m, 30H); 0.89 (t, 3H, J=6.60 Hz).
  • 62
  • [ 60-33-3 ]
  • [ 58186-27-9 ]
  • [ 1177393-70-2 ]
YieldReaction ConditionsOperation in experiment
87% With novozym 435; In toluene; at 20℃; for 48h;4A molecular sieves; Example 1 :Preparation of ldebenone Linoleate (1a)(EX00011-037) ldebenone (2a, R = R1 = Me, n= 9; 547 mg; 1.6 mmol) was dissolved in10 mL of toluene. Linoleic acid (2.18 g; 4.9 equiv) was added followed by 641 mg of 4A molecular sieves and 309 mg of Novozym 435. The reaction mixture was stirred at ambient temperature for 2 days, at which point tic analysis (1 :1 ethyl acetate:heptane eluant) indicated no remaining idebenone. The solids were removed by filtration and the precipitate washed with toluene. The combined filtrate and washes were concentrated at reduced pressure. The residue was dissolved in heptane (22 mL) and washed with a mixture of11 mL of methanol and 11 mL of 10% aqueous potassium carbonate. The organic layer was further washed with a mixture of 11 mL of methanol, 4 mL of saturated sodium bicarbonate, and 7 mL of water. The organic layer was then dried with sodium sulfate and concentrated to afford 0.84 g (87%) of 1a (R = R1 = Me, n= 9).1H NMR (CDCI3) delta 5.40-5.30 (m, 4H); 4.049 (t, 2H, J = 6.87 Hz); 3.988 (s, 6H); 2.768 (t, 2H, J = 5.77 Hz); 2.45 (m, 2H); 2.288 (t, 2H1 J = 7.42 Hz); 2.08- 2.01 (m, 3H); 2.009 (s, 3H); 1.64-1.57 (m, 3H); 1.40-1.29 (m, 30H); 0.89 (t, 3H, J = 6.60 Hz).
  • 63
  • [ 58186-27-9 ]
  • [ 117677-69-7 ]
  • [ 1220282-54-1 ]
YieldReaction ConditionsOperation in experiment
Example 1Synthesis of <strong>[58186-27-9]Idebenone</strong> Dipalmitoyl Glycerate; This example provides a synthesis of 3-oxo-3-(9-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)monyloxy)propane-1,2-diyl dipalmitate (Compound 5; idebenone dipalmitoyl glycerate), which is representative of the carboxylic acid-substituted idebenone derivatives of the present invention. A starting material in the idebenone dipalmitoyl glycerate synthesis is benzyl acrylate (Compound 1), which may be subjected to various chemical reactions in order to form a crude diol oil (Compound 2). This diol is then subjected to an acylation reaction with palmitoyl chloride in the presence of various reagents (TEA, 4-DMAP, and CH2Cl2) in order to form a tri-ester, Compound 3. This product is then reacted with ethyl acetate (AcOEt) in the presence of various reagents (H2 and Pd-C (10%)) to form an acid, Compound 4. Then, Compound 4 is combined with a solvent (SOCl2/CH2Cl2) and reacted with idebenone in the presence of various reagents (TEA, 4-DMAP, and CH2Cl2) to form the end product, Compound 5 (idebenone dipalmitoyl glycerate).The dihydroxylation of benzyl acrylate (Compound 1) to form Compound 2 may be performed in various ways. One method is to react benzyl acrylate (1.0 mmol) with 0.4 mol % of potassium osmate dihydrate, three equivalents of potassium ferricyanate (III), and three equivalents of potassium carbonate in a 1:1 mixture of t-butanol and water. (Angew. Chem. Int. Ed. Engl. 1996, 35, 448-451). Stir the reaction at room temperature for approximately 21 hours. It may be necessary to add more of the osmate catalyst to drive the reaction to completion. After an aqueous workup, the crude diol (Compound 2) is obtained in an almost quantitative yield.Another method for dihydroxylation of benzyl acrylate is to use non-volatile potassium osmate dihydrate. (J. Org. Chem. 1998, 6094). Benzyl acrylate (1.0 mmol) was reacted with 0.5 mol % of potassium osmate dihydrate, 1.3 equivalents of N-methylmorpholine N-oxide (NMO) in a 1:1:1 solvent mixture of water:acetone:acetonitrile at room temperature. The reaction was complete in 12 hours. After an aqueous workup, the crude diol (Compound 2) was obtained as an oil in nearly quantitative yield. The proton NMR indicated that the crude diol was 95% pure. This crude oil became dark brown after standing overnight at room temperature. Probably a small amount of residual osmate was present in the crude diol and was responsible for the color change. The work-up conditions may be modified to include a bisulfite wash and/or a plug filtration to move any baseline impurities. If the darkening cannot be eliminated, the crude diol (Compound 2) may be taken directly on to the tri-ester (Compound 3) and purified at the acid stage of Compound 4.The crude oil was purified by column chromatography to identify the diol (Compound 2). This compound did not ionize with electrospray LC/MS. The proton NMR confirmed the desired product, Compound 2, had been prepared.
  • 64
  • [ 1251831-79-4 ]
  • [ 58186-27-9 ]
  • 65
  • [ 1286209-74-2 ]
  • [ 58186-27-9 ]
  • 66
  • [ 112-47-0 ]
  • [ 58186-27-9 ]
  • 67
  • [ 53463-68-6 ]
  • [ 58186-27-9 ]
  • 68
  • [ 13019-22-2 ]
  • [ 58186-27-9 ]
  • 69
  • [ 72326-72-8 ]
  • [ 58186-27-9 ]
  • 70
  • [ 504-30-3 ]
  • [ 58186-27-9 ]
  • [ 1360077-50-4 ]
YieldReaction ConditionsOperation in experiment
With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; toluene;Inert atmosphere; Under argon atmosphere, <strong>[58186-27-9]Idebenone</strong> (1 eq), PPh3 (1 eq) and an alcohol (1 eq) were dissolved in dry THF and a 40% solution of DEAD (1 eq) in toluene was added. The reaction was monitored either by LCMS and/or TLC. After the reaction was finished, the solvent was removed by evaporation and the residue was purified first with flash-chromatography (AcOEt/cyclohexane) and then with preparative HPLC-MS.
  • 71
  • [ 58186-27-9 ]
  • [ 40203-94-9 ]
  • [ 1360079-85-1 ]
YieldReaction ConditionsOperation in experiment
In toluene; at 90℃; for 24h; <strong>[58186-27-9]Idebenone</strong> (1.65 g, 4.87 mmol) and methyl (S)-(-)-2-isocyanato-3-phenylpropionate (1.00 g, 4.87 mmol) were dissolved in toluene (50 ml) and stirred at 90C for 1 d. The solvent was removed under reduced pressure.The product was purified by column chromatography.
  • 72
  • [ 58186-27-9 ]
  • [ 1360078-29-0 ]
  • 73
  • [ 58186-27-9 ]
  • [ 1360078-47-2 ]
  • 74
  • [ 58186-27-9 ]
  • [ 1360078-58-5 ]
  • 75
  • [ 58186-27-9 ]
  • [ 1360078-65-4 ]
  • 76
  • [ 58186-27-9 ]
  • [ 1360079-74-8 ]
  • [ 1360079-76-0 ]
YieldReaction ConditionsOperation in experiment
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; To a solution of idebenone (51 mg, 0.15 mmol) and intermediate 60h (136 mg, 0.15 mmol) in DCM (3 ml) was added EDC (44 mg, 0.23 mmol) and DMAP (4 mg, 0.03 mmol). The resulting solution was stirred at room temperature overnight. The reaction mixture was diluted with DCM and extracted twice with 5% citric acid and water. The combined aqueous phase was extracted twice with DCM. The combined organic layer was washed with brine, dried over sodium sulfate and the solvent was removed under reduced pressure. The crude product was purified by column chromatography.
  • 77
  • [ 58186-27-9 ]
  • [ 1431987-01-7 ]
  • 78
  • [ 58186-27-9 ]
  • [ 1431987-49-3 ]
  • 79
  • [ 58186-27-9 ]
  • [ 1431986-91-2 ]
YieldReaction ConditionsOperation in experiment
75% With 2,6-di-tert-butyl-4-methylpyridine; trifluoromethylsulfonic anhydride; tetrabutylammonium nitrate; In dichloromethane; at -70℃; for 2h; A dry 500 mL round bottom flask containing 2-(10-hydroxydecyl)-5,6- dimethoxy-3-methyl cyclohexa-2,5-diene- l ,4-dione (7g, 20.7 mmol), 2,6-di- tert-butyl-4-methylpyridine (6.37 g, 31 mmol, 1.5 eq) and tetrabutylammonium nitrate (7.5 g, 24.8 mmol, 1.2 eq) in dichloromethane (250 mL) was cooled to -70C and maintained at this temperature with stirring during the dropwise addition of a solution of triflic anhydride (4 mL, 24.8 mmol, 1.2 eq) in dichloromethane (30 mL). The reaction mixture was stirred at -70C for 2 h, and then allowed to warm to room temperature. The reaction mixture was washed with H2O. The organic phase was dried over anhydrous sodium sulfate and the solvent removed in vacuum. The residue was purified by column chromatography (SNAP 340, gradient system from 4/6 ethyl acetate/n-hexane to 60/40 ethyl acetate/n-hexane) to give the titled compound as a reddish oil (6.0 g, 75%).
75% With 2,6-di-tert-butyl-4-methylpyridine; trifluoromethylsulfonic anhydride; tetrabutylammonium nitrate; In dichloromethane; at -70℃; for 2h; Method A A dry 500 mL round bottom flask containing 2-(10-hydroxydecyl)-5,6- dimethoxy-3 -methyl cyclohexa-2,5-diene-l,4-dione (7g, 20.7 mmol), 2,6-di-tert- butyl-4-methylpyridine (6.37 g, 31 mmol, 1.5 eq) and tetrabutylammonium nitrate (7.5 g, 24.8 mmol, 1.2 eq) in dichloromethane (250 mL) was cooled to -70C and maintained at this temperature with stirring during the dropwise addition of a solution of triflic anhydride (4 mL, 24.8 mmol, 1.2 eq) in dichloromethane (30 mL). The reaction mixture was stirred at -70C for 2 h, and then allowed to warm to room temperature. The reaction mixture was washed with H2O. The organic phase was dried over anhydrous sodium sulfate and the solvent removed in vacuum. The residue was purified by column chromatography (SNAP 340, gradient system from 4/6 ethyl acetate/n-hexane to 60/40 ethyl acetate/n-hexane) to give the titled compound as a reddish oil (6.0 g, 75%).
  • 80
  • [ 58186-27-9 ]
  • [ 1431987-51-7 ]
  • 81
  • [ 58186-27-9 ]
  • [ 1431987-52-8 ]
  • 82
  • [ 58186-27-9 ]
  • di-tert-butyl 2,3-dimethoxy-5-methyl-6-(10-(nitrooxy)undecyl)-1,4-phenylene dicarbonate [ No CAS ]
  • 83
  • [ 58186-27-9 ]
  • [ 1431987-02-8 ]
  • 84
  • [ 24424-99-5 ]
  • [ 58186-27-9 ]
  • [ 1431987-50-6 ]
YieldReaction ConditionsOperation in experiment
79% With triethylamine; In tetrahydrofuran; at 0 - 20℃; Step 2: Synthesis of tert-butyl 2-(10-hydroxydecyl)-5,6-dimethoxy-3- methyl- 1 ,4-phenylene dicarbonate To a stirred solution of 2-(10-hydroxydecyl)-5,6-dimethoxy-3- methylbenzene- 1 ,4-diol (1 g, 2.94 mmol) and Et3N (0.9 mL, 6.47 mmol, 2.2 eq) in dry THF (40 mL) was added at 0C a solution of Boc2O (1.34 g, 6.17 mmol, 2.1 eq) in dry THF (5 mL). The reaction was stirred overnight at rt and then diluted with H2O/EtOAc. The organic layer was separated and washed with HCl 0.1M, water, saturated aqueous NaHCO3, water and brine, dried on sodium sulfate, filtered and evaporated. The residue was purified by flash chromatography (Biotage SP4, SNAP 100 column, EtOAc in Hex from 20% to 40% in 10 CV) to afford the title compound as a colorless oil (1.26 g, Yield: 79%).
  • 85
  • [ 58186-27-9 ]
  • [ 811-68-7 ]
  • 2,3-dimethoxy-5-methyl-6-(10-((trifluoromethyl)thio)decyl)cyclohexa-2,5-diene-1,4-dione [ No CAS ]
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