Home Cart 0 Sign in  
X

[ CAS No. 14690-00-7 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
3d Animation Molecule Structure of 14690-00-7
Chemical Structure| 14690-00-7
Chemical Structure| 14690-00-7
Structure of 14690-00-7 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 14690-00-7 ]

Related Doc. of [ 14690-00-7 ]

Alternatived Products of [ 14690-00-7 ]
Product Citations

Product Details of [ 14690-00-7 ]

CAS No. :14690-00-7 MDL No. :MFCD00075493
Formula : C10H14O3 Boiling Point : -
Linear Structure Formula :HOCH2CH(OCH2C6H5)CH2OH InChI Key :UDIPIOHLDFSMLR-UHFFFAOYSA-N
M.W : 182.22 Pubchem ID :203567
Synonyms :

Calculated chemistry of [ 14690-00-7 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 13
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.4
Num. rotatable bonds : 5
Num. H-bond acceptors : 3.0
Num. H-bond donors : 2.0
Molar Refractivity : 49.24
TPSA : 49.69 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -7.22 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.81
Log Po/w (XLOGP3) : 0.27
Log Po/w (WLOGP) : 0.4
Log Po/w (MLOGP) : 0.68
Log Po/w (SILICOS-IT) : 1.45
Consensus Log Po/w : 0.92

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -1.15
Solubility : 12.9 mg/ml ; 0.0706 mol/l
Class : Very soluble
Log S (Ali) : -0.87
Solubility : 24.3 mg/ml ; 0.133 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.25
Solubility : 1.02 mg/ml ; 0.00562 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.64

Safety of [ 14690-00-7 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P233-P260-P261-P264-P271-P280-P302+P352-P304-P304+P340-P305+P351+P338-P312-P321-P332+P313-P337+P313-P340-P362-P403-P403+P233-P405-P501 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 14690-00-7 ]

* 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 [ 14690-00-7 ]

[ 14690-00-7 ] Synthesis Path-Downstream   1~100

  • 1
  • [ 105409-38-9 ]
  • [ 14690-00-7 ]
YieldReaction ConditionsOperation in experiment
82% With potassium carbonate In methanol for 0.25h; Ambient temperature;
With sodium hydroxide
  • 2
  • [ 41128-90-9 ]
  • [ 14690-00-7 ]
YieldReaction ConditionsOperation in experiment
With sulfuric acid
Multi-step reaction with 2 steps 1: acetic acid / anschliessend Erwaermen mit konz. wss. HCl 2: methanol. NaOH
  • 3
  • [ 544-77-4 ]
  • [ 14690-00-7 ]
  • [ 18678-94-9 ]
YieldReaction ConditionsOperation in experiment
(i) Na, xylene, (ii) /BRN= 1748533/; Multistep reaction;
In <i>N</i>-methyl-acetamide; water; Petroleum ether 28 3-(Hexadecyloxy)-2-(benzyloxy)-1-propanol EXAMPLE 28 3-(Hexadecyloxy)-2-(benzyloxy)-1-propanol To a suspension of about 14.26 g of washed about 50% sodium hydride in about 500 ml of dimethylformamide was added about 49.2 g of 2-(benzyloxy)-1,3-propanediol over about 20 minutes. The mixture was stirred for about 40 minutes, then cooled to about 0° C. and about 95.13 g of hexadecyl iodide were added. After standing about 10 minutes, the mixture was stirred at room temperature for about 3 hours, then filtered through celite and diluted with about 1000 ml of water. This mixture was extracted with petroleum ether. The ether extract was dried and the solvent removed giving an oil. This oil was chromatographed on a column of florisil, eluding first with petroleum ether and then successively with about 5% and about 10% ether in petroleum ether to elute the product, giving about 28.8 g of the desired title compound as a light yellow oil.
In <i>N</i>-methyl-acetamide; water; Petroleum ether 27 3-(Hexadecyloxy)-2-(benzyloxy)-1-propanol EXAMPLE 27 3-(Hexadecyloxy)-2-(benzyloxy)-1-propanol To a suspension of about 14.26 g of washed about 50% sodium hydride in about 500 ml of dimethylformamide was added about 49.2 g of 2-(benzyloxy)-1,3-propanediol over about 20 minutes. The mixture was stirred for about 40 minutes, then cooled to about 0° C. and about 95.13 g of hexadecyl iodide were added. After standing about 10 minutes, the mixture was stirred at room temperature for about 3 hours, then filtered through celite and diluted with about 1000 ml of water. This mixture was extracted with petroleum ether. The ether extract was dried and the solvent removed giving an oil. This oil was chromatographed on a column of florisil, eluding first with petroleum ether and then successively with about 5% and about 10% ether in petroleum ether to elute the product, giving about 28.8 g of the desired title compound as a light yellow oil.
  • 4
  • [ 68728-34-7 ]
  • [ 14690-00-7 ]
YieldReaction ConditionsOperation in experiment
100% With hydrogenchloride In methanol for 1h; Heating;
87% With sulfuric acid In ethanol; water for 5h; Heating;
86.7% With hydrogenchloride In methanol; water at 20℃; for 6h; Cooling with ice; Synthesis of 1-4 The 1-3 (218 · 9g, 809. 78mmol) was dissolved in 800ml of methanol ,hydrochloric acid was added dropwise 100ml6N room temperature under iceStirring for about 6h, TLC showed the reaction was complete , the solvent wasevaporated under reduced pressure and benzaldehyde to give crude product 1-4 ,the crude product with n- heptane Dioxane was stirred crystallization give a white solid 127. 93g, yield 86.7% ;
80% With Dowex 50X8 (H(+) form) In methanol for 4h; Heating;
75% With hydrogenchloride; water In methanol for 0.333333h; Reflux;
63.8% With hydrogenchloride In methanol for 1h; Reflux; 192 Synthesis of compound 192.4 Synthesis of compound 192.4. To a solution of 192.3 (5.0 g, 18.51 mmol, leq) in MeOH was added 1M HC1 and reaction was refluxed for lh. Upon completion of the reaction, mixture was concentrated to provide 192.5 . (2.5 g, 63.8%). MS(ES): m/z 183.20 [M+H]+.
With sulfuric acid In ethanol
With hydrogenchloride In water Yield given;
With hydrogenchloride In tetrahydrofuran; water for 1.5h; Heating; Yield given;
13 g With sulfuric acid In ethanol; water for 2h; Heating;
18.0 g With hydrogenchloride In tetrahydrofuran; water for 2h; Heating;
With hydrogenchloride; water In tetrahydrofuran for 2h; Heating / reflux; 13.2 Sodium hydride (1 g, 60 % in mineral oil, 42 mmol, 1.67 g) is suspended in freshly distilled THF (100 ml_), and the mixture is cooled in an ice/H2O bath. 1 ,3-0- Benzylidene glycerol (28 mmol) is added in portions, and the mixture is stirred for 15 min. Benzyl bromide (40 mmol) is added via a syringe, and the reaction is stirred at 0 °C to room temperature overnight. Approximately half of the THF is evaporated under reduced pressure, and 20 ml_ of H2O and 60 mL of 10 % aqueous HCI are added. The mixture is refluxed for 2 h, cooled to room temperature, and is poured into 10 mL of saturated aqueous Na2CO3. The solution is extracted with ethyl acetate (3 times with 20 mL). The extracts are dried over Na2SO4 and evaporated and purified by column chromatography (eluantfrom hexane/ethyl acetate (50/50) ethyl acetate 100%).
With hydrogenchloride In tetrahydrofuran; water at 23℃;
With hydrogenchloride; water In tetrahydrofuran at 23℃; 16 Example 162-(Benzyloxy)propane-1,3-diol (17). To a solution of 16 (2.5 g, 13.8 mmol) in dry THF (20 mL), cooled to 0° C., NaH (60% in mineral oil, 0.56 g, 14 mmol) was added portionwise. After 30 min, tetra-n-butylammonium iodide (51 mg, 0.14 mmol) and a solution of benzyl bromide (1.65 mL, 13.9 mmol) in THF (5 mL) were added. The reaction mixture was stirred at 23° C. for 3 h, afterward it was poured into ice. The organic solvent was removed in vacuo and the aqueous phase was extracted with CHCl3. The organic extracts were dried (Na2SO4) and the solvent was removed. The crude 5-(benzyloxy)-2-phenyl-1,3-dioxane thus obtained was dissolved in a 1:1 mixture of THF and H2O (60 mL) and to the resulting solution, 6 N HCl was slowly added to the resulting solution. After stirring at 23° C., the reaction mixture was brought to pH 8 by addition of a saturated solution of NaHCO3, the solvent was removed and the aqueous phase was extracted with diethyl ether. The organic extracts were dried and evaporated and the residue was purified by flash-column chromatography (EtOAc 2: Hex 1) to afford the title compound as a colourless oil in quantitative yield. Physical and spectroscopic data are consistent with those reported in the literature (Hronowski, L. J. J.; et al., Synthesis and characterization of 1-O-_-lactosyl-(R,S)-glycerols and 1,3-di-O-_lactosylglycerol. Carbohydrate Res. 1989, 190, 203-218).
Stage #1: 5-benzyloxy-2-phenyl-1,3-dioxane With hydrogenchloride In methanol Stage #2: With sodium hydroxide In methanol
12.1 g With DOWEX (50WX8 H+) In methanol; water at 80℃; for 5h; 4.4. 2-(Benzyloxy)propane-1,3-diol (5) To a solution of 2-phenyl-1,3-dioxan-5-ol (3) (18 g, 100 mmol) in dry DMF (500 ml) cooled to 10 C under argon atmosphere,NaH (60% suspension in mineral oil; 6 g, 150 mmol, 1.5 eq.) was added. Reaction flask was filled with argon again and the mixture was stirred for 30 min. to preform sodium salt of alcohol. Benzylbromide (14.6 ml, 125 mmol, 1.25 eq.) was added and reaction flask was filled with argon again. The resulting mixture was warmed up to room temperature and stirred overnight. Water(75 ml) was added and mixture was stirred for 30 min. Solvents were evaporated in vacuo and the residue was codistilled with toluene (3). Crude material was suspended in EtOAc (250 ml)and mixture of saturated solution of NH4Cl (40 ml) and water(160 ml). Water phase was separated and extracted with EtOAc(2 150 ml). The organic phase was collected (250 + 150+ 150 ml) and washed by water (2 200 ml), followed by brine(1 200 ml) and dried over MgSO4. The solution was filtered and evaporated in vacuo. The residue (crude substance 4, brownoil) was diluted in MeOH (320 ml) and water (80 ml). DOWEX(50WX8 H+, 10 g) was added and mixture was heated at 80 Cand stirred for 5 h. Reaction mixture was cooled down to room temperature and filtered through the frit (S3), evaporated in vacuoand codistilled with toluene (3). Crude product was purified by flash chromatography (silica gel; eluent CHCl3/MeOH, gradient 2-5%) to obtained 12.1 g (66%) of 5 as colourless oil. Reaction was monitored by TLC and presence of product was confirmed by GC-MS. Pure product was used in the next reaction step without additional characterisation.

Reference: [1]Wang, Qi; Loennberg, Harri [Journal of the American Chemical Society, 2006, vol. 128, # 33, p. 10716 - 10728]
[2]Surles; Wykle; O'Flaherty; Salzer; Thomas; Snyder; Piantadosi [Journal of Medicinal Chemistry, 1985, vol. 28, # 1, p. 73 - 78]
[3]Current Patent Assignee: NANJING FORESTRY UNIVERSITY - CN103554064, 2016, B Location in patent: Paragraph 0032; 0037; 0039
[4]Vrbovska, Silvie; Holy, Antonin; Pohl, Radek; Masojidkova, Milena [Collection of Czechoslovak Chemical Communications, 2006, vol. 71, # 4, p. 543 - 566]
[5]Park, Yun Ji; Yang, Jung Woon [Green Chemistry, 2019, vol. 21, # 10, p. 2615 - 2620]
[6]Current Patent Assignee: SCHROEDINGER LLC; NIMBUS THERAPEUTICS INC - WO2017/40757, 2017, A1 Location in patent: Paragraph 00875
[7]Plackett,P. [Australian Journal of Chemistry, 1964, vol. 17, p. 101 - 108]
[8]Grum-Grzhimailo,M.A. et al. [Journal of Organic Chemistry USSR (English Translation), 1968, vol. 4, p. 1113 - 1116][Zhurnal Organicheskoi Khimii, 1968, vol. 4, p. 1157 - 1161]
[9]Marinier, Anne; Deslongchamps, Pieere [Tetrahedron Letters, 1988, vol. 29, # 48, p. 6215 - 6218]
[10]Marinier; Deslongchamps [Canadian Journal of Chemistry, 1992, vol. 70, # 9, p. 2350 - 2364]
[11]Nali, Micaela; Rindone, Bruno; Bosone, Enrico; Farina, Paolo; Innocenti, Sergio; Valcavi, Umberto [Gazzetta Chimica Italiana, 1986, vol. 116, # 1, p. 25 - 28]
[12]Ray III, William C.; Grinstaff, Mark W. [Macromolecules, 2003, vol. 36, # 10, p. 3557 - 3562]
[13]Current Patent Assignee: CEDARS-SINAI HEALTH SYSTEM - WO2008/106640, 2008, A1 Location in patent: Page/Page column 57-58
[14]Location in patent: experimental part Ghosh, Aran K.; Gemma, Sandra; Baldridge, Abigail; Wang, Yuan-Fang; Kovalevsky, Andrey Yu.; Koh, Yashiro; Weber, Irene T.; Mitsuya, Hiroaki [Journal of Medicinal Chemistry, 2008, vol. 51, # 19, p. 6021 - 6033]
[15]Current Patent Assignee: PURDUE UNIVERSITY SYSTEM - US2011/118330, 2011, A1 Location in patent: Page/Page column 26-27
[16]Xu, Xiaoxu; Liu, Xiaofeng; Li, Qun; Hu, Jianshe; Chen, Qifan; Yang, Liqun; Lu, Yanhua [RSC Advances, 2017, vol. 7, # 23, p. 14176 - 14185]
[17]Špaček, Petr; Keough, Dianne T.; Chavchich, Marina; Dračínský, Martin; Janeba, Zlatko; Naesens, Lieve; Edstein, Michael D.; Guddat, Luke W.; Hocková, Dana [Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 15, p. 4008 - 4030]
  • 5
  • [ 100-44-7 ]
  • [ 1708-40-3 ]
  • [ 14690-00-7 ]
YieldReaction ConditionsOperation in experiment
65% With potassium hydroxide at 75℃; for 3h;
(i) aq. KOH, (ii) (acid hydrolysis); Multistep reaction;
  • 8
  • [ 108-05-4 ]
  • [ 14690-00-7 ]
  • [ 109429-01-8 ]
  • [ 109429-00-7 ]
YieldReaction ConditionsOperation in experiment
92% at 8℃; for 4h; Lipase P; with further acetates;
Pseudomonas sp. lipase (SAM-2); Yield given. Yields of byproduct given. Title compound not separated from byproducts;
  • 9
  • [ 108-22-5 ]
  • [ 14690-00-7 ]
  • [ 105409-38-9 ]
  • [ 109429-01-8 ]
YieldReaction ConditionsOperation in experiment
1: 53% 2: 175 mg In chloroform at 28℃;
1: 175 mg 2: 53% In chloroform at 28℃; for 27h;
  • 10
  • [ 108-22-5 ]
  • [ 14690-00-7 ]
  • [ 109429-01-8 ]
YieldReaction ConditionsOperation in experiment
53% In chloroform at 28℃; for 24h; lipase from Pseudomonas sp.;
  • 11
  • [ 37860-51-8 ]
  • [ 14690-00-7 ]
  • 15-Benzyloxy-1,4,7,10,13-pentaoxa-cyclohexadecane [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium t-butanolate In <i>tert</i>-butyl alcohol at 60℃; for 2h; Yield given;
  • 12
  • [ 123-86-4 ]
  • [ 14690-00-7 ]
  • [ 109429-01-8 ]
  • [ 109429-00-7 ]
YieldReaction ConditionsOperation in experiment
23% In 1,1,1-trichloroethane at 25℃; for 3h;
  • 14
  • [ 140-11-4 ]
  • [ 14690-00-7 ]
  • [ 109429-01-8 ]
  • [ 109429-00-7 ]
YieldReaction ConditionsOperation in experiment
28% In 1,1,1-trichloroethane at 25℃; for 3h;
  • 15
  • [ 14690-00-7 ]
  • [ 80197-23-5 ]
YieldReaction ConditionsOperation in experiment
72% With phosphorus trichloride In chloroform at 5℃; for 4h;
  • 16
  • [ 14690-00-7 ]
  • [ 88946-00-3 ]
YieldReaction ConditionsOperation in experiment
53% With 2,6-dimethylpyridine; trichlorophosphate In dichloromethane for 18h; Ambient temperature;
With trichlorophosphate In dichloromethane 1 The procedure of Buchnea (Buchnea, 1973) was followed essentially as described. Briefly, 2-benzyloxy-1,3-propanediol (Aldrich) was reacted with an equimolar amount of phosphorus oxychloride (Aldrich) in methylene chloride. The resulting 2-benzyl-1,3 cGP was treated with hydrogen under the catalysis of Pd black in methanol to remove the benzyl residue. The 1,3 cGP, isolated as the Ba salt, was pure on paper chromatography (n-propanol: ammonia: water 6:3:1, Rf=0.52).1,3 cGP was also produced by the cleavage of phosphatidyl glycerol (PG) with phospholipase C as described (Shinitzky et al., 1993). The product, termed 1,3,cGP(E) had a trace of approx. 10-20% α-GP as indicated by paper chromatography.
With 1,8-diazabicyclo[5.4.0]undec-7-ene; trichlorophosphate In dichloromethane at 0 - 30℃; 3 Weigh intermediate 23 11.88g 65.22mmol,Mix DBU 29.98g 195.66mmol and 200ml dichloromethane evenly,Cooled in an ice water bath, the temperature of the reaction liquid is controlled at 0-5°C,The phosphorus oxychloride intermediate 22 10.00g 65.22mmol andA solution made of 20ml of dichloromethane was slowly added dropwise to the reaction solution,Control the dripping in 20-30min,Raise the temperature of the reaction solution to room temperature 20-30°C,Stir the reaction for 0.5-1.0hr,After the reaction is over, cool in an ice water bath,The temperature of the reaction liquid is controlled at 0-5°C,A solution made of 6.52g of trifluoroethanol, 65.22mmol and 10ml of dichloromethane was slowly added dropwise to the reaction solution,Control the dripping in 10-20min, and raise the temperature of the reaction solution to room temperature 20-30,The reaction was stirred for 0.5-1.0 hr, and the precipitate was removed by filtration to obtain a dichloromethane solution. After the organic phase was distilled off under reduced pressure, it was distilled under reduced pressure.130-140/5mmHg, collect fractions,15.5 g of colorless oily liquid was obtained, which was product intermediate 19. The yield was 72.86%. Product purity: 98.74%
  • 17
  • [ 14690-00-7 ]
  • [ 141-78-6 ]
  • [ 109429-01-8 ]
  • [ 109429-00-7 ]
YieldReaction ConditionsOperation in experiment
20% In 1,1,1-trichloroethane at 25℃; for 3h;
  • 18
  • [ 105409-40-3 ]
  • [ 14690-00-7 ]
  • [ 115930-16-0 ]
  • [ 115930-16-0 ]
YieldReaction ConditionsOperation in experiment
61% With phosphate buffer; pig liver esterase In acetone at 30℃; Yields of byproduct given;
61% With phosphate buffer; pig liver esterase In acetone at 30℃; Yield given. Yields of byproduct given;
  • 19
  • [ 114838-37-8 ]
  • [ 14690-00-7 ]
YieldReaction ConditionsOperation in experiment
92% With sulfuric acid In 1,4-dioxane for 3h; Heating;
77% With sulfuric acid In 1,4-dioxane; water Reflux; 1.3 Step 3 Synthesis of 2-benzyloxypropane-1,3-diol [(2-benzyloxy-3-trityloxy-propoxy) -diphenyl-methyl] benzene (3.30 g, 4.95 mmol) obtained in step 2 was dissolved in 1,4-dioxane (20 mL) and 10%. Aqueous sulfuric acid solution (6 mL) was added, and the mixture was heated under reflux overnight. Water (15 mL) was added while lowering the temperature to room temperature and stirring, and the precipitated solid was separated by filtration. The solid obtained by concentrating the filtrate was purified by silica gel chromatography (hexane / ethyl acetate) to give the title compound (699 mg, 3.84 mmol, yield 77%) as a white solid.
With toluene-4-sulfonic acid In methanol Yield given;
With acetic acid at 100℃; for 0.5h; Yield given;
57.7 g With sulfuric acid; water In 1,4-dioxane at 95℃; for 16h; 1 Synthesis of 2-(benzyloxy)propane-l,3-diol (4): Synthesis of 2-(benzyloxy)propane-l,3-diol (4): To a stirred solution of (((2- (Benzyloxy)propane-l,3-diyl)bis(oxy))bis(methanetetrayl))hexabenzene 3 (360 g, crude, 0.434 mol) in 1,4-dioxane (1.6 Lt), 10%H2SO4 (560 mL) was added and stirred the mixture at 95°C for 16h. After completion of reaction on TLC, pH of the reaction mixture was adjusted to 5-6 by using aqueous saturated NaHCC solution and filtered. The filtrate was extracted with EtOAc (2 x 2 Lt) and the organic layer was washed with water (500 mL) followed by brine (200 mL). It was dried over anhydrous Na2S04 and concentrated under vacuum. The resulting crude was purified by column chromatography on silica gel (100-200 mesh) using 2% MeOH-DCM as eluent to afford 4 as a brown solid (57.7 g, 58%). 1H NMR (400 MHz, DMSO-d6): δ 7.37-7.28 (m, 5H), 4.61 (s, 2H), 4.56 (m, 2H), 3.54-3.45 (m, 4H), 3.39 (m, 1H).

  • 20
  • [ 105434-68-2 ]
  • [ 14690-00-7 ]
  • 1-O-butyryl-2-O-benzylglycerol [ No CAS ]
  • 1-O-butyryl-2-O-benzylglycerol [ No CAS ]
YieldReaction ConditionsOperation in experiment
40% With phosphate buffer; pig liver esterase In acetone at 30℃; Yields of byproduct given;
40% With phosphate buffer; pig liver esterase In acetone at 30℃; Yield given. Yields of byproduct given;
  • 21
  • [ 14690-00-7 ]
  • [ 98-59-9 ]
  • [ 19945-19-8 ]
YieldReaction ConditionsOperation in experiment
97% With triethylamine In dichloromethane at 0℃; for 23h;
85% With sodium hydroxide In tetrahydrofuran at 3 - 5℃;
84% In pyridine
  • 22
  • [ 14690-00-7 ]
  • [ 77-76-9 ]
  • [ 3391-30-8 ]
YieldReaction ConditionsOperation in experiment
68% In 1,2-dimethoxyethane for 65h; Heating;
  • 23
  • [ 14690-00-7 ]
  • [ 122-79-2 ]
  • [ 109429-01-8 ]
  • [ 109429-00-7 ]
YieldReaction ConditionsOperation in experiment
88% In 1,1,1-trichloroethane at 25℃; for 3h;
  • 24
  • [ 14690-00-7 ]
  • [ 58479-61-1 ]
  • [ 145842-04-2 ]
YieldReaction ConditionsOperation in experiment
51% With 1H-imidazole In tetrahydrofuran Ambient temperature;
  • 25
  • [ 14690-00-7 ]
  • [ 4753-07-5 ]
  • [ 125471-64-9 ]
YieldReaction ConditionsOperation in experiment
52% With mercury(II) cyanide In nitromethane; benzene 1.) 20 deg C, 1 h 2.) 40 deg C, 2.5 h;
  • 26
  • [ 14690-00-7 ]
  • 1',2',3',6',2,3,4,6-octa-O-acetyl-β-D-lactose [ No CAS ]
  • [ 125471-64-9 ]
  • 3-O-acetyl-2-O-benzyl-1-O-(2,3,6,2',3',4',6'-hepta-O-acetyl-β-lactosyl)-(R,S)-glycerol [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 40% 2: 29% With trimethylsilyl trifluoromethanesulfonate; 4 A molecular sieve In dichloromethane at 23℃; for 2h;
  • 27
  • [ 14690-00-7 ]
  • [ 677-24-7 ]
  • [ 104532-43-6 ]
YieldReaction ConditionsOperation in experiment
49% With 2,6-dimethylpyridine In benzene for 18h; Ambient temperature;
  • 29
  • [ 14690-00-7 ]
  • [ 637-88-7 ]
  • 3,12-Bis-benzyloxy-1,5,10,14-tetraoxa-dispiro[5.2.5.2]hexadecane [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% With toluene-4-sulfonic acid In benzene Heating;
  • 30
  • [ 14690-00-7 ]
  • [ 196497-40-2 ]
  • 7,15-Bis-benzyloxy-1,5,9,13-tetraoxa-cyclohexadecane-3,11-diol [ No CAS ]
YieldReaction ConditionsOperation in experiment
97% With sodium hydride In tetrahydrofuran Heating;
  • 31
  • [ 14690-00-7 ]
  • [ 338459-08-8 ]
  • [ 338459-09-9 ]
YieldReaction ConditionsOperation in experiment
35% With sodium hydride In tetrahydrofuran at 20℃; for 0.5h;
  • 32
  • [ 93625-24-2 ]
  • [ 14690-00-7 ]
YieldReaction ConditionsOperation in experiment
50% With 8-aminopyrene-1,3,6-trisulfonic acid, trisodium salt In methanol; water for 48h; Heating;
  • 33
  • [ 14690-00-7 ]
  • [ 425431-04-5 ]
  • 4-(5-benzyloxy-[1,3]dioxan-2-yl)-6-bromo-7-hydroxy-chromen-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With pyridinium p-toluenesulfonate; magnesium sulfate In toluene at 110℃;
  • 34
  • [ 14690-00-7 ]
  • [ 572-09-8 ]
  • 1,3-di-O-(2',3',4',6'-tetra-O-acetyl-β-D-glucopyranosyl)-2-O-benzyl-sn-glycerol [ No CAS ]
YieldReaction ConditionsOperation in experiment
46% With mercury(II) cyanide; mercury dibromide In acetonitrile at 20℃;
  • 35
  • [ 14690-00-7 ]
  • Tetradecanoic acid (S)-2-(benzyloxy-diisopropylamino-phosphanyloxy)-1-tetradecanoyloxymethyl-ethyl ester [ No CAS ]
  • Tetradecanoic acid (S)-2-(benzyloxy-{2-benzyloxy-3-[benzyloxy-((S)-2,3-bis-tetradecanoyloxy-propoxy)-phosphoryloxy]-propoxy}-phosphoryloxy)-1-tetradecanoyloxymethyl-ethyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% Stage #1: 2-O-benzylglycerol; Tetradecanoic acid (S)-2-(benzyloxy-diisopropylamino-phosphanyloxy)-1-tetradecanoyloxymethyl-ethyl ester With 1H-tetrazole for 1h; Stage #2: With tert.-butylhydroperoxide at -40 - 20℃; Further stages.;
  • 36
  • 2-(2-bromoethoxy)tetrahydropyran [ No CAS ]
  • [ 14690-00-7 ]
  • [ 680219-93-6 ]
YieldReaction ConditionsOperation in experiment
71% With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 24h;
71% With sodium hydride In N,N-dimethyl-formamide at 20℃; for 12h;
  • 37
  • [ 88-14-2 ]
  • [ 14690-00-7 ]
  • 2-(benzyloxy)propane-1,3-diyl di(2-furoate) [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% With dmap; dicyclohexyl-carbodiimide In tetrahydrofuran at 20℃;
  • 38
  • [ 14690-00-7 ]
  • [ 35995-55-2 ]
YieldReaction ConditionsOperation in experiment
87% With carbon tetrabromide; triphenylphosphine In dichloromethane at 0 - 20℃; for 2h;
77% With carbon tetrabromide; triphenylphosphine In dichloromethane at 0℃; for 2h;
59% With carbon tetrabromide; triphenylphosphine In dichloromethane at 0℃; for 2.5h; Inert atmosphere; 5 Synthesis of [2-Bromo-l-(bromomethyl)ethoxy]methylbenzene (11) Synthesis of [2-Bromo-l-(bromomethyl)ethoxy]methylbenzene (11) [00179] To a solution of 2-benzyloxypropane-l,3-diol (24.3 g, 129.36 mmol) in anhydrous CH2CI2 (350 mL) under argon atmosphere at 0 °C was added PI13P (72.177 g, 272.43 mmol) followed by CBn (91.258 g, 272.43 mmol) (one portion addition caused a huge gas generation). The reaction mixture was stirred at 0 °C for 2.5 h. To the reaction mixture was added water (150 mL) and dichloromethane (600 mL). The organic layer was separated, dried over sodium sulfate, filtered and concentrated under reduced pressure. Then, 10% ether in hexane (500 mL) was added, sonicated and filtered. The solid cake was washed with 10% ether in hexane (300 mL). The solid was discarded and the combined filtrates were concentrated under reduced pressure to give the crude product. The crude product was purified by flash chromatography (loaded in CH2CI2) (330g S1O2, eluting 0 to 4% ether in hexane) to afford [2-bromo-l- (bromomethyl)ethoxy]methylbenzene (23.39 g, 59%) as a colorless liquid. 1H NMR (500 MHz, Chloroform-d) d 7.49 - 7.30 (m, 5H), 4.70 (s, 2H), 3.83 (p, J = 5.2 Hz, 1H), 3.60 (d, J = 5.2 Hz, 4H). ESI-MS m/z calc. 305.92548, NO MS was observed. Retention time: 5.47 minutes (LC Method C).
With carbon tetrabromide; triphenylphosphine In dichloromethane 506.1 2-Benzyloxy-l,3-propanediol (15.000 g, 82.32 mmol) was dissolved in CH2C12 (500ml) and carbon tetrabromide (81.90 g, 247 '.0 mmol) and triphenylphosphine (64.77 g, 247.0 mmol) were added. The mixture was stirred overnight and concentrated. The reaction was suspended in hexanes and filtered and evaporated to afford the title compound.

  • 39
  • [ 14690-00-7 ]
  • [ 541-41-3 ]
  • [ 86629-66-5 ]
YieldReaction ConditionsOperation in experiment
67% Stage #1: 2-O-benzylglycerol; chloroformic acid ethyl ester In tetrahydrofuran at 0℃; for 0.25h; Stage #2: With triethylamine In tetrahydrofuran at 0 - 20℃; for 3h;
65% With triethylamine In tetrahydrofuran at 0 - 20℃; for 4.5h; Inert atmosphere;
With triethylamine In tetrahydrofuran at 0℃;
  • 40
  • 2-(benzyloxy)propane-1,3-diyl di(2-furoate) [ No CAS ]
  • [ 14690-00-7 ]
  • (+)-2-benzyloxy-3-hydroxypropan-1-yl 2-furoate [ No CAS ]
  • (-)-2-benzyloxy-3-hydroxypropan-1-yl 2-furoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
26% With Candida antarctica lipase; fraction B; water In di-isopropyl ether at 30℃; for 84h; Title compound not separated from byproducts;
  • 41
  • [ 14690-00-7 ]
  • Tetradecanoic acid (R)-2-[chloro-(2-chloro-phenoxy)-phosphoryloxy]-1-tetradecanoyloxymethyl-ethyl ester [ No CAS ]
  • [ 628722-33-8 ]
YieldReaction ConditionsOperation in experiment
72% In dichloromethane at 20℃; for 6h;
  • 42
  • [ 854300-83-7 ]
  • [ 14690-00-7 ]
  • [ 854300-84-8 ]
YieldReaction ConditionsOperation in experiment
With 1H-tetrazole In dichloromethane at 20℃; for 6h;
With 1H-tetrazole 1 First, commercially available (i?)-(+)-3-benzyloxy-l,2-propanediol was reacted with 1- bromohexane in the presence of sodium hydride (60% in oil dispersion) in dimethyl formamide (DMF). This reaction was followed by debenzylation via catalytic hydrogenolysis (H2/Pd-C) which provided 1,2-di- O-hexyl-sw-glycerol in a 89% yield. The next step involved reacting 1,2-di-O-hexyl-in-glycerol with a bifunctional phosphitylating reagent ΛζTV-diisopropylmethylphosphonamidic chloride in the presence of ΛζΛf-diisopropylethylamine (DIPEA) in dichloromethane at room temperature to give l,2-di-0-hexyl-.s7z- glycero-ΛζiV-diisopropyl methylphosphoramidite. 1 ,2-di-O-hexyl-j/z-glycero-NN-diisopropyl methylphosphoramidite was then reacted with 2-benzyloxy-l,3-propanediol in the presence of l//-tetrazole to provide a phosphite triester. In situ oxidation of the phosphite trimester, with m-chloroperbenzoic acid (mCPBA) at -40 0C, afforded 2-0-benzyl-l,3-bis-(l,2-di-0-hexyl-j«-glycero-3-phosplioryl)glycerol dimethyl ether in the form of a colorless oil. A yield of 79% was achieved after purification of the 2-0- benzyl-l,3-bis-(l,2-di-O-hexyl-JH-glycero-3-phosphoryl)glycerol dimethyl ether on a silica gel column (hexane-ethyl acetate, 8:2-6:4). Purification was followed by hydrogenolysis by reacting 2-0-benzyl-l,3- bis-(l,2-di-0-hexyl-jn-glycero-3-phosphoryl)glycerol dimethyl ether with H2/Pd-C at 50 psi for 2 hours. This reaction furnished a 96% yield of l,3-bis-(l,2-di-O-hexyl-.57J-glycero-3-phosphoryl)glycerol dimethyl ether in the form of a colorless oil. The central hydroxyl functionality of l,3-bis-(l,2-di-O-hexyl-.57z- glycero-3-phosphoryl)glycerol dimethyl ether (cardiolipin analogue) was then reacted with succinic anhydride in the presence of triethylamine and 4-dimethylamino pyridine (DMAP) in 1,2-dichloroethane to provide a 79% yield of l,3-bis-(l,2-di-0-hexyl-sκ-glycero-3-phosphoryl)-2-succinylglycerol dimethyl ether. l,3-bis-(l,2-di-0-hexyl-j7z-glycero-3-phosphoryl)-2-succinylglycerol dimethyl ether was then reacted with 4-N-3'-O-bis(fert-butoxycarbonyl)gemcitabine in the presence of //.JV-dicyclohexyl carbodimide (DCC) and DMAP in dichloromethane at room temperature for 8 hours. This reaction was followed by purification on a silica gel column (hexane-ethyl acetate, 7:3-4:6) which afforded a 84% yield of 4-N-3'-(9-di(tert-butoxycarbonyl)-5'-C'-succinyl-[2-0-l,3-bis-(l,2-di-0-hexyl-5iw-glycero)-3-phosphoryl glycerol dimethyl ether] gemcitabine. The protecting groups of 4-7V-3'-O-di(tert-butoxycarbonyl)-5'-O- succinyl-[2-0-l,3-bis-(l,2-di-C>-hexyl-1siH-glycero)-3-phosphoryl glycerol dimethyl ether] gemcitabine were removed using trifluororacetic acid (TFA) in dichloromethane at room temperature. The reaction solution was neutralized with 5% aqueous sodium bicarbonate at 0 0C, extracted with dichloromethane and then concentrated. Purification of the crude compound on a silica gel column (chloroform-methanol, 98:2-96:4) afforded an 80% yield of pure 5'-0-succinyl-[2-0-l,3-bis-(l,2-di-0-hexyl-«z-glycero)-3- phosphorylglycerol dimethyl ether] gemcitabine in the form of a colorless viscous oil. This final product was characterized by 1H NMR, 13C NMR, IR and Mass Spectroscopy. The purity was checked by HPLC and elemental analysis.
  • 43
  • [ 14690-00-7 ]
  • [ 108-24-7 ]
  • [ 105409-38-9 ]
  • [ 109429-01-8 ]
  • [ 109429-00-7 ]
YieldReaction ConditionsOperation in experiment
58% With BOC-Pmh-D-Pro-D-Asp(Obut)-Tyr(OBn)-D-Phe-OMe; N-ethyl-N,N-diisopropylamine In dichloromethane; toluene at -55℃;
  • 44
  • [ 358-23-6 ]
  • [ 14690-00-7 ]
  • trifluoro-methanesulfonic acid 2-benzyloxy-3-trifluoromethanesulfonyloxy-propyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In acetonitrile at -20 - -10℃;
  • 45
  • [ 14690-00-7 ]
  • [ 35717-98-7 ]
  • [ 927814-91-3 ]
YieldReaction ConditionsOperation in experiment
65% Stage #1: 2-O-benzylglycerol With sodium hydride In N,N-dimethyl-formamide at 0℃; Stage #2: bis(2-propyl)-p-toluenesulfonyloxymethylphosphonate In N,N-dimethyl-formamide at 20℃; for 8h;
  • 46
  • [ 4530-20-5 ]
  • [ 14690-00-7 ]
  • C24H36N2O9 [ No CAS ]
YieldReaction ConditionsOperation in experiment
96.7% Stage #1: BOC-glycine; 2-O-benzylglycerol With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 0.0833333h; Stage #2: With dmap In dichloromethane at 0 - 20℃; for 72.25h; 1.B.1 Synthesis of Di-TFA salt ofbis(gfycine)-l,3-diglyceride (Compound 1.1); Synthesis was conducted using carbodiimide technique and benzyl-protected monomer was introduced into the PEA backbone (Fig. 2). Boc-glycine (5.25g, 30.0 mmol) was dissolved in dry dichloromβthane (50.0 ml) and added 2-0-benzyIglycerol (l.82g, 10.0 mmol) followed by DCC (6.18g, 30.0 mmol), stirred the mixture for 5 minutes at room temperature. 4-Dimethylaminopyridine (DMAP) (0.24g, 0.2 mmol) was dissolved in dichloromethane (4.0 mL) and added slowly at 00C under argon. The reaction was stirred another 15 minutes at O0C and continued at room temperature for 3 days. After complete consumption of compound 2-O-benzylglycerol (TLC, hexane:ethyl acetate in 6:4 volume ratio), the formed urea derivative was removed through glass frit, washed with dichloromethane (3x25 ml), and combined filtrate was concentrated under vacuum. The oily product compound was purified by column chromatography using hexane/ethyl acetate as eluents (at volume ratio of 8:2 then 7:3). AU fractions were combined, concentrated and dried, yielding which gave 4.8 g (96.7%) of pure product (Compound 1.1a). Deprotection of Boc-group was conducted in dichloromethane (25 ml) by slowly adding TFA (25 ml) at 0°C, under argon while stirring. After complete addition, the ice bath was removed and stirring was continued for 2 h at room temperature. Consumption of starting material was monitored by TLC (using Hexane.εthylacetate, in a volume ratio of 6:4). Pouring of the reaction mixture into cold ether yielded a white solid, which was washed with hexanes, filtered, and then washed again with ether (2x20 mL). The compound was dried under vacuum at 350C. The yield of the purified monomer salt (Compound 1.1) was 85.28% (4.23 g).
  • 47
  • [ 14690-00-7 ]
  • [ 49676-79-1 ]
  • C28H46O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With AK lipase In acetonitrile at 50℃; for 18h;
  • 48
  • [ 925932-27-0 ]
  • [ 14690-00-7 ]
  • [ 338459-11-3 ]
YieldReaction ConditionsOperation in experiment
19% With sodium hydride In N,N-dimethyl-formamide at 60℃;
  • 49
  • [ 14690-00-7 ]
  • [ 171597-35-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: lipase / propan-2-ol 2: 1.) POCl3, 3.) H2O, 4.) H2 / 4.) Pd(OH)2/C / 1.) Et3N, 2.) pyridine, 4.) H2O, Ch3OH
Multi-step reaction with 2 steps 1: diisopropyl ether / 4 h / Ambient temperature; lipase Amano P from Pseudomonas fluorescens 2: POCl3
Multi-step reaction with 2 steps 1: diisopropyl ether / 1.5 h / Ambient temperature; lipase Amano P from Pseudomonas fluorescens 2: POCl3
Multi-step reaction with 2 steps 1: lipase / diisopropyl ether 2: POCl3

  • 50
  • [ 14690-00-7 ]
  • [ 18678-98-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 1.) K / 1.) C6H6, reflux, 4 h, 2.) C6H6, reflux, overnight 2: 1.) POCl3, Et3N, 2.) pyridine / 1.) CHCl3, 60-65 deg C, 30 min, 2.) CHCl3, RT, 5 h
Multi-step reaction with 2 steps 1: 1.) Na / 1.) toluene, 60 degC, 2.) toluene, 80 degC, 16 h 2: 1.) triethylamine / 1.) CHCl3, 2.) CHCl3, CH3CN, ethanol, 30 h, r.t.
Multi-step reaction with 6 steps 2: 1.) NaH / 1.) DMF, 2.) 12 h, room temp. 3: K2CO3 / methanol / 4 h / Ambient temperature 4: Et3N / trichloroethene / 4 h 5: 1M Na2CO3 6: CHCl3; dimethylformamide; propan-2-ol; H2O / 12 h / 50 °C
Multi-step reaction with 2 steps 1: (i) Na, xylene, (ii) /BRN= 1748533/ 2: (i) Et3N, (ii) /BRN= 956566/

  • 51
  • [ 100-44-7 ]
  • [ 14690-00-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 1.) K / 1.) C6H6, reflux, 7 h, 2.) C6H6, reflux, overnight 2: 87 percent / H2SO4 / H2O; ethanol / 5 h / Heating
Multi-step reaction with 2 steps 1: 1.) 80percent NaH / 1.) toluene, room temp., 15 min, 2.) toluene, reflux, 6 h 2: 13 g / conc. H2SO4 / H2O; ethanol / 2 h / Heating
  • 52
  • [ 14690-00-7 ]
  • [ 187976-16-5 ]
YieldReaction ConditionsOperation in experiment
With trichlorophosphate In dichloromethane 1 The procedure of Buchnea (Buchnea, 1973) was followed essentially as described. Briefly, 2-benzyloxy-1,3-propanediol (Aldrich) was reacted with an equimolar amount of phosphorus oxychloride (Aldrich) in methylene chloride. The resulting 2-benzyl-1,3 cGP was treated with hydrogen under the catalysis of Pd black in methanol to remove the benzyl residue.The 1,3 cGP, isolated as the Ba salt, was pure on paper chromatography (n-propanol: ammonia: water 6:3:1, Rf=0.52).
  • 53
  • [ 869884-63-9 ]
  • [ 14690-00-7 ]
  • 2-benzyl-1,3-di(Myr-[G2]-PGLSA)2-glycerol [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With dicyclohexyl-carbodiimide; 4-(dimethylamino)pyridinium tosylate In dichloromethane at 20℃; for 16h; 81 0.85 g (0.62 mmol) of compound Myr-[G2]-PGLSA-acid was dissolved in 75 mL Of CH2Cl2 with 0.05 g (0.26 mmol) of 2-benzyl-glycerol, 0.08 g (0.26 mmol) of DPTS, and 0.16 g (0.77 mmol) of DCC. The reaction was stirred at RT for 16 hours. The DCU precipitate was filtered and the solution was evaporated. The residue was resuspended in 50 mL of ethanol, cooled to 0 0C for 6 hours and filtered. The precipitate was purified by column chromatography (20-50% EtOAc in hexanes) to yield 0.63 g of product (85% yield). Rf = 0.17 (30% EtOAc in hexanes). 1H NMR (CDCl3): δ 0.81-0.88 (t, 24H, -CH3), 1.17-1.34 (m, 160Η, myristic -CH2-), 1.52-1.63 (m, 16Η, C(=O)-CH2-CH2-CH2-), 2.24-2.32 (t, 16H, C(=O)-CH2-CH2-), 2.58-2.66 (m, 24H, succinic -CH2-CH2), 3.77-3.85 (m, 1Η, - CH2-CH-CH2-), 4.04-4.38 (m, 28H, -CH2-CH-CH2-), 4.59-4.65 (s, 2Η, benzyl -CH2-), 5.17-5.34 (m, 6Η, -CH2-CH-CH2-), 7.25-7.34 (m, 5H, aromatic CH) ppm. MALDI-MS: 2933.4 m/z (M+Na+) (theory: 2933.0 m/z (M+Na4)). Elemental analysis: C, 67.92%; Η, 9.79% (theory: C, 67.69%; Η, 9.77%). SEC: Mw = 4388, Mn = 4258, PDI = 1.03.
  • 54
  • [ 112-96-9 ]
  • [ 14690-00-7 ]
  • 3-(N-octadecylcarbamoyloxy)-2-benzyloxy-1-propanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride In pyridine; hexane; chloroform P.6.3 3-(N-Octadecylcarbamoyloxy)-2-benzyloxypropyl 2-thiazolioethyl phosphate (3) In 20 ml of pyridine is dissolved 3.64 g of β-benzylglycerol and 5.9 g of octadecyl isocyanate is added. The mixture is stirred at room temperature overnight. The pyridine is then distilled off and diluted hydrochloric acid and chloroform are added to the residue. The chloroform layer is separated, dried and concentrated. The residue is purified by silica gel chromatography [eluent: chloroform-ether (10:1)]. Recrystallization of a main product from n-hexane gives 4.1 g of 3-(N-octadecylcarbamoyloxy)-2-benzyloxy-1-propanol. M.p. 52°-54° C.
  • 55
  • [ 629-93-6 ]
  • [ 14690-00-7 ]
  • [ 86008-21-1 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; <i>N</i>-methyl-acetamide; water; Petroleum ether 29 2-(Benzyloxy)-3-(octadecyloxy)-1-propanol EXAMPLE 29 2-(Benzyloxy)-3-(octadecyloxy)-1-propanol To a suspension of about 26.07 g of washed about 50% sodium hydride in about 1000 ml of dimethylformamide was added about 90 g of 2-(benzyloxy)-1,3-propanediol with stirring under argon. An about 187.88 g portion of octadecyl iodide and about 150 ml of tetrahydrofuran were added and the thick mixture was stirred with a glass rod, and then with magnetic stirring for about 3 hours. Water was then added and the mixture was extracted with ether. The ether extract was washed with brine, dried and filtered through a pad of florisil. The solvent was removed and the residue chromatographed on florisil, eluding first with petroleum ether, then with about 10% ether in petroleum ether and finally eluding the product with about 30% ether in petroleum ether, giving about 73.3 g of the desired title compound as a waxy solid. By following the methods outlined above in Examples 28 and 29, 2-(benzyloxy)-1,3-propanediol is alkylated with the indicated alkyl iodides to provide the 1-propanol derivatives listed in Table III below.
In tetrahydrofuran; <i>N</i>-methyl-acetamide; water; Petroleum ether 28 2-(Benzyloxy)-3-(octadecyloxy)-1-propanol EXAMPLE 28 2-(Benzyloxy)-3-(octadecyloxy)-1-propanol To a suspension of about 26.07 g of washed about 50% sodium hydride in about 1000 ml of dimethylformamide was added about 90 g of 2-(benzyloxy)-1,3-propanediol with stirring under argon. An about 187.88 g portion of octadecyl iodide and about 150 ml of tetrahydrofuran were added and the thick mixture was stirred with a glass rod, and then with magnetic stirring for about 3 hours. Water was then added and the mixture was extracted with ether. The ether extract was washed with brine, dried and filtered through a pad of florisil. The solvent was removed and the residue chromatographed on florisil, eluding first with petroleum ether, then with about 10% ether in petroleum ether and finally eluding the product with about 30% ether in petroleum ether, giving about 73.3 g of the desired title compound as a waxy solid. By following the methods outlined above in Examples 27 and 28, 2-(benzyloxy)-1,3-propanediol is alkylated with the indicated alkyl iodides to provide the 1-propanol derivatives listed in Table III below.
  • 56
  • [ 97-97-2 ]
  • [ 14690-00-7 ]
  • 5-benzyloxy-2-chloromethyl-1,3-dioxane [ No CAS ]
YieldReaction ConditionsOperation in experiment
With toluene-4-sulfonic acid 38.b b. A mixture of 5.0 g of 2-benzyloxy-1,3-propanediol, 3.5 g of chloroacetaldehyde dimethyl acetal and 0.3 g of p-toluenesulfonic acid was heated via oil bath through the temperature range 25° to 130° C in a three-necked, round-bottomed flask equipped with stirrer, thermometer and condenser. The by-product methanol, removed by distillation during the course of reaction, amounted to 63% of theory. The reaction mixture was cooled to room temperature and dissolved in ether. The ether solution was washed with 10% sodium carbonate and then with water. After drying over anhydrous sodium sulfate, the ether was removed under reduced pressure. Distillation of the crude oil gave 3.3 g of 5-benzyloxy-2-chloromethyl-1,3-dioxane; b.p. 100°-105° C/0.025 mm Hg; nD25 1.5228. The nmr spectrum was consistent with the assigned structure and showed the cis isomer content to be 30 +- 5%, the remainder being the trans isomer. Analysis: Calc'd. for C12 H15 ClO3: C 59.38; H 6.23; Found: C 59.56; H 6.49.
  • 57
  • [ 98-01-1 ]
  • [ 14690-00-7 ]
  • 5-benzyloxy-2-(furan-2-yl)-1,3-dioxane [ No CAS ]
YieldReaction ConditionsOperation in experiment
In benzene 34 A mixture of 18.2 g of 2-benzyloxy-1,3-propanediol (Example 34A), 9.6 g of furaldehyde and 4 g of Dowex 50W * 8 resin (H+ form) in 100 ml of benzene was refluxed until the theoretical amount of water was formed (1.8 g). By-product water was removed as an azeotropic mixture which distilled from the reaction vessel during refluxing (2.2 ml collected). After the ionic resin was removed, the benzene solution was washed with two 50-ml portions of one percent ammonium hydroxide, dried with magnesium sulfate, filtered and evaporated under reduced pressure to give 13 g of an oil. The oil was vacuum distilled and those fractions boiling at 128°-130° C/10-4 mm Hg(nD25 =1.5412 and nD25 =1.5415) were collected as oils which crystallized to give a total of 6.0 g of 5-benzyloxy-2-(2-furyl)-1,3-dioxane, m.p. 50°-52° C. Analysis: Calc'd for C15 H16 O4: C 69.21; H 6.20; Found: C 69.44; H 6.00.
  • 58
  • acetophenene [ No CAS ]
  • [ 14690-00-7 ]
  • [ 144-55-8 ]
  • 5-benzyloxy-2-methyl-2-phenyl-1,3-dioxane [ No CAS ]
YieldReaction ConditionsOperation in experiment
With toluene-4-sulfonic acid In water; toluene; benzene 51 5-Benzyloxy-2-methyl-2-phenyl-1,3-dioxane EXAMPLE 51 5-Benzyloxy-2-methyl-2-phenyl-1,3-dioxane A mixture of 18.2 g of 2-benzyloxy-1,3-propanediol, 12.1 g of acetophenene and 0.1 g of p-toluenesulfonic acid in 75 ml of benzene and 75 ml of toluene was heated under a Dean-Stark apparatus until 2.0 ml of water had been collected. The mixture was washed twice with 75 ml of 5% aqueous sodium bicarbonate, then with water. After drying over magnesium sulfate, the solution was concentrated under reduced pressure to give 1.6 g of oil which crystallized on standing to give a solid, m.p. 76°-79° C. Recrystallization gave 5-benzyloxy-2-methyl-2-phenyl-1,3-dioxane, m.p. 87°-88°. The ir and nmr spectra were consistent with the assigned structure. The nmr spectrum indicated 50% cis isomer and 50% trans isomer.
  • 59
  • [ 14690-00-7 ]
  • [ 1700-37-4 ]
  • 5-Benzyloxy-2-(3-benzyloxyphenyl)-1,3-dioxane [ No CAS ]
YieldReaction ConditionsOperation in experiment
With toluene-4-sulfonic acid In benzene 16 5-Benzyloxy-2-(3-benzyloxyphenyl)-1,3-dioxane EXAMPLE 16 5-Benzyloxy-2-(3-benzyloxyphenyl)-1,3-dioxane A mixture of 2-benzyloxy-1,3-propanediol (18.0 g, 0.1 mole), 3-benzyloxybenzaldehyde (21.2 g, 0.1 mole) and p-toluenesulfonic acid (0.1 gram) in 150 ml of benzene was heated at reflux under a Dean-Stark apparatus until collection of water ceased (1.8 ml). The solution was washed with 2% sodium bicarbonate (2 * 100 ml) and with water (2 * 100 ml), then dried over magnesium sulfate and concentrated to give 34.2 g of brown oil. Recrystallization from benzene-ligroin gave 22.5 g of solid, m.p. 77°-78° C. nmr analysis of this solid indicated it to contain 31% cis-5-benzyloxy-2-(3-benzyloxyphenyl)-1,3-dioxane.
  • 60
  • [ 1191-95-3 ]
  • [ 14690-00-7 ]
  • [ 913696-17-0 ]
YieldReaction ConditionsOperation in experiment
98.2% With toluene-4-sulfonic acid In benzene for 2h; Heating / reflux; 9.d To a round-bottom flask containing a benzene (50 ml) solution of the 2-(benzyloxy)propane-1,3-diol (5.0 g, 27.4 mmol) obtained in the step (9c), cyclobutanone (2.33 ml, 30.6 mmol), and p-toluenesulfonic acid monohydrate (100 mg, 0.53 mmol), a reflux cooling tube equipped with the Dean-Stark water separator was attached. The mixture was under refluxed for 2 hours. To the resultant mixture, triethylamine (0.4 ml, 0.72 mmol) was added and the mixture was concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography (NH silica gel, elution solvent: heptane, heptane/ethyl acetate=5/1) to obtain the title compound (6.3 g, yield: 98.2%) as a light yellow oil. 1H NMR(400 MHz, CDCl3) δppm; 1.70-1.79(2H, m), 2.20-2.29(4H, m), 3.44-3.50(1H, m), 3.64-3.69(2H, m), 3.92(2H, dd, J=4, 12 Hz), 4.58(2H, s), 7.27-7.39(5H, m).
  • 61
  • 5-(benzyloxy)-2,2-dimetheyl-1,3-dioxane [ No CAS ]
  • [ 14690-00-7 ]
YieldReaction ConditionsOperation in experiment
93.8% With DOWEX 50W-X8 In methanol at 20℃; for 2h; 9.c (9c) 2-(benzyloxy)propane-1,3-diol To a methanol (50 ml) solution of the 5-(benzyloxy)-2,2-dimethyl-1,3-dioxane (6.5 g, 29.2 mmol) obtained in the step (9b), DOWEX 50W-X8 (5 g) was added and stirred at room temperature. After 2 hours, the reaction mixture was filtered and concentrated to obtain the title compound (5.0 g, 93.8%) as a colorless oil. 1H NMR(400 MHz, CDCl3) δppm; 3.60-3.65(1H, m), 3.74(2H, dd, J=5, 12 Hz), 3.82(2H, dd, J=4, 12 Hz), 4.67(2H, s), 7.29-7.40(5H, m).
  • 62
  • 1-O-hexyl-2-O-methyl-sn-glycero-N,N-diisopropyl methylphosphoramidite [ No CAS ]
  • [ 14690-00-7 ]
  • C32H60O11P2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With 1H-tetrazole 2 Alkylation of commercially available (R)-(+)-2,2-dimethyl- 1 ,3-dioxolane-methanol with 1 - bromohexane in the presence of sodium hydride (60% in an oil dispersion) in tetrahydrofuran (THF) followed by deprotection of the isopropylidene group with 2N HCl in methanol provided 1-O-hexyl- glycerol. Tritylation of l-O-hexyl-glycerol,using trityl chloride in the presence of triethylamine and DMAP in dichloromethane, gave l-O-hexyl-3-O-trityl glycerol. Methylation of the trityl derivative with iodomethane, in the presence of sodium hydride in THF, followed by detritylation with p-toluenesulfonic acid monohydrate, in THF, provided l-O-hexyl-2-O-methylglycerol with a 63% yield. The next step involved the reaction of l-O-hexyl-2-O-methyl-.siH-glycerol with N,N-diisopropylmethylphosphonamidic chloride in the presence of N, jV-diisopropylethylamine (DIPEA) in dichloromethane at room temperature. This reaction resulted in l-O-hexyl-2-O-methyl-sw-glycero-ΛζN-diisopropyl methylphosphoramidite which was then reacted with 2-benzyloxy-l,3-propanediol, in the presence of li-tetrazole, to provide a phosphite triester. In situ oxidation of the phosphite trimester, with 7«-chloroperbenzoic acid (mCPBA) at -40 0C, afforded 2-0-benzyl-l,3-bis-(l-0-hexyl-2-0-methyl-j«-glycero-3-phosphoryl)glycerol dimethyl ether. Purification of this product on a silica gel column (hexane-ethyl acetate, 8:2-4:6) resulted in 2-O-benzyl- l,3-bis-(l-0-hexyl-2-O-methyl--SM-glycero-3-phosphoryl)glycerol dimethyl ether as a colorless oil in 87% yield. Hydrogenolysis of 2-0-benzyl- 1 ,3 -bis-( 1 -0-hexyl-2-O-methyl--.s7i-glycero-3 -phosphoryl)glycerol dimethyl ether, with H2/Pd-C at 50 psi for 2 hours, resulted in l,3-bis-(l-O-hexyl-2-O-rnethyl--.57z-glycero- 3-phosphoryl)glycerol dimethyl ether as a colorless oil in 96% yield. The central hydroxyl functionality of l,3-bis-(l-0-hexyl-2-0-methyl~5'«-glycero-3-phosphoryl)glycerol dimethyl ether (cardiolipin analogue) was reacted with succinic anhydride in the presence of triethylamine and 4-dimethylamino pyridine (DMAP) in 1,2-dichloroethane which provided l,3-bis-(l-0-hexyl-2-0-methyl--s«-glycero-3-phosphoryl)- 2-succinyl glycerol dimethyl ether in a 68% yield. l,3-bis-(l-O-hexyl-2-(9-methyl~i'«-glycero-3- phosphoryl)-2-succinyl glycerol dimethyl ether was then coupled with 4-N-3'-O-bis(tert- butoxycarbonyl)gemcitabine in the presence of Af N-dicyclohexyl carbodimide (DCC) and DMAP in dichloromethane at room temperature for 8 hours. This was followed by purification on a silica gel column (dichloromethane-acetone, 8:2-6:4) which afforded 4-7V-3'-O-di(tert-butoxycarbonyl)-5'-O-succinyl-[2-O- l,3-bis-(l-O-hexyl-2-O-methyl -5iκ-glycero)-3-phosphoryl glycerol dimethyl ether] gemcitabine in a 60% yield. The protecting groups were removed using trifluororacetic acid (TFA) in dichloromethane at room temperature. The reaction solution was neutralized with 5% aqueous sodium bicarbonate at 0 0C, extracted with dichloromethane and concentrated. Purification of the crude compound on a silica gel column (chloroform-methanol, 98:2-9:1) afforded pure 5'-O-succinyl-[2-O-l,3-bis-(l-O-hexyl-2-O-methyl -5r«- glycero)-3-phosphorylglycerol dimethyl ether] gemcitabine as a viscous oil in a 70% yield. The product was characterized by 1H NMR, 13C NMR, IR and HRMS. The purity was checked by HPLC.
  • 63
  • 1,2-O-dimyristyl-sn-glycero-N,N-diisopropyl methylphosphoramidite [ No CAS ]
  • [ 14690-00-7 ]
  • C74H144O11P2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With 1H-tetrazole 6 l,2-O-dimvristyl-5κ-glycerol was reacted with Λζ Λf-diisopropylmethylphosphonarnidic chloride in the presence of ΛζN-diisopropylethylamrne (DIPEA) in dichloromethane at room temperature to give 1,2-O-dimyristyl-Η-glycero-ΛζTV-diisopropyl methylphosphoramidite which was subsequently reacted with 2-benzyloxy-l,3-propanediol, in the presence of liZ-tetrazole, to provide a phosphite triester. In situ oxidation of the phosphite trimester, with »z-chloroperbenzoic acid (OTCPBA) at -40 0C, afforded 2-0- benzyl-l,3-bis-(l,2- O-dimyristyl -,s72-glycero-3-phosphoryl)glycerol dimethyl ether. l,3-bis-(l,2- O- dimyristyl -,yrø-glycero-3-phosphoryl)glycerol dimethyl ether was then purified on a silica gel column (hexane-ethyl acetate, 1:0-1:1), resulting in a colorless oil with a 90% yield. Hydrogenolysis of 2-0- benzyl-l,3-bis-(l,2- O-dimyristyl -sn-glycero-3-phosphoryl)glycerol dimethyl ether, with H2/Pd-C at 50 psi for 5 hours, furnished l,3-bis-(l,2- O-dimyristyl -."/j-glycero-S-phosphory^glycerol dimethyl ether as a colorless oil in a 98% yield. The central hydroxyl functionality of l,3-bis-(l,2-O-dimyristyl-iΗ-glycero-3- phosphoryl)glycerol dimethyl ether (cardiolipin analogue) was reacted with succinic anhydride in the presence of triethylamine and 4-dimethylamino pyridine (DMAP) in 1,2-dichloroethane to provide 1,3-bis- (1,2- O-dimyristyl -.sra-glycero-3-phosρhoryl)-2-succinylglycerol dimethyl ether in a 88% yield. 1,3-bis- (l,2-0-dimyristyl-jK-glycero-3-phosphoryl)-2-succinylglycerol dimethyl ether was coupled with 4-N-3'-O- bis(fert-butoxycarbonyi)gemcitabine in the presence of ΛζN-dicyclohexyl carbodimide (DCC) and DMAP in dichloromethane at room temperature for 8 hours. This reaction was followed by purification on a silica gel column (hexane-ethyl acetate, 7:3-1:1) which afforded 4-7V-3'-0-di(tert-butoxycarbonyl)-5'-0-succinyl- [2-O-l,3-bis-(l,2- O-dimyristyl -j»-glycero)-3-ρhosρhoryl glycerol dimethyl ether] gemcitabine with a 73% yield. The protecting groups were removed using trifluororacetic acid (TFA) in dichloromethane at room temperature. The reaction solution was neutralized with 5% aqueous sodium bicarbonate at 0 0C, extracted with dichloromethane and concentrated. Purification of the crude compound on a silica gel column (chloroform-methanol, 98:2-96:4) afforded pure 5'-O-succinyl-[2-O-l,3-bis-(l,2- 0-dimyristyl -sn- glycero)-3-phosphorylglycerol dimethyl etherjgemcitabine as a white crystalline solid with a 69% yield. The product was characterized by 1H NMR. The purity was checked by HPLC and elemental analysis.
  • 64
  • 1-O-tetradecyl-2-O-methyl-sn-glycero-N,N-diisopropyl methylphosphoramidite [ No CAS ]
  • [ 14690-00-7 ]
  • C48H92O11P2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With 1H-tetrazole 7 Alkylation of commercially available (R)-(-)-2,2-dimethyl-l,3-dioxolane-methanol with 1- bromotetradecane in the presence of sodium hydride (60% in oil dispersion) in No.,7V-dimethylformamide (DMF) followed by deprotection of isopropylidene group, with 2N HCl in methanol, provided 1-0- tetradecyl-glycerol. Tritylation of 1-0-tetradecyl-glycerol was accomplished by using trityl chloride in the presence of triethylamine and DMAP in dichloromethane. This resulted in l-0-tetradecyl-3-0-trityl glycerol. The trityl derivative was methylated with iodomethane, in the presence of sodium hydride in THF. This reaction was followed by detritylation with p-toluenesulfonic acid monohydrate in THF which provided l-0-tetradecyl-2-0-methylglycerol with a 65% yield. The next step involved the reaction of l-O- tetradecyl-2-0-methyl-J7J-glycerol with ΛζΛf-diisopropylmethylphosphonamidic chloride, in the presence of ΛζN-diisopropylethylamine (DIPEA) in dichloromethane at room temperature, to give l-O-tetradecyl-2-0- methyl-^z-glycero-ΛζiV-diisopropyl methylphosphoramidite which was subsequently reacted with 2- benzyloxy-l,3-propanediol in the presence of 1/7-tetrazole to provide a phosphite triester. In situ oxidation of the phosphite trimester, with m-chloroperbenzoic acid (mCPBA) at -40 0C, afforded 2-0-benzyl-l,3-bis- (l-0-tetradecyl-2-0-methyl-5w-glycero-3-phosphoryl)glycerol dimethyl ether which was then purified on a silica gel column (methylene chloride-ethyl acetate, 8:2-6:4). This resulted in 2-0-benzyl-l,3-bis-(l-0- tetradecyl-2-0-methyl- κ-glycero-3-phosphoryl)glycerol dimethyl ether as a colorless oil with a 68% yield. Hydrogenolysis of2-0-benzyl-l,3-bis-(l-0-tetradecyl-2-0-methyl-i'M-glycero-3-phosphoryl)glycerol dimethyl ether, with H2/Pd-C at 50 psi for 2 hours, furnished l,3-bis-(l-0-tetradecyl-2-0-methyl-5n- glycero-3-phosphoryl)glycerol dimethyl ether as a colorless oil with a 96% yield. The central hydroxyl functionality of l,3-bis-(l-0-tetradecyl-2-0-methyl-57z-glycero-3-phosphoryl)glycerol dimethyl ether (cardiolipin analogue) was reacted with succinic anhydride in the presence of triethylamine and 4- dimethylamino pyridine (DMAP) in 1,2-dichloroethane to provide l,3-bis-(l-0-tetradecyl-2-0-methyl-.«- glycero-3-ρhosρhoryl)-2-succinyl glycerol dimethyl ether with a 79% yield. l,3-bis-(l-0- tetradecyl -2-O- methyl--.yra-glycero-3-phosphoryi)-2-succinyl glycerol dimethyl ether was coupled with 4-N-3 '-0-bis(fert- butoxycarbonyl)gemcitabine in the presence of N,N-dicyclohexyl carbodimide (DCC) and DMAP in dichloromethane at room temperature for 8 hours. This reaction was followed by purification on a silica gel column (hexane-acetone, 8.5:1.5-7:3) which afforded 4-N-3'-O-di(tert-butoxycarbonyl)-5'-O-succinyl-[2-0- l,3-bis-(l-0-tetradecyl-2-0-methyl-5κ-glycero)-3-phosphoryl glycerol dimethyl ether] gemcitabine with a 60% yield. The protecting groups were removed using trifluororacetic acid (TFA) in dichloromethane at room temperature. The reaction solution was neutralized with 5% aqueous sodium bicarbonate at 0 0C, extracted with dichloromethane and concentrated. Purification of the crude compound on a silica gel column (chloroform-methanol, 98:2-9.5:0.5) afforded pure 5'-O-succinyl-[2-O-l,3-bis-(l-0-tetradecyl-2-O- methyl-jn-glycero)-3-ρhosphorylglycerol dimethyl ether] gemcitabine as a viscous oil with a 70% yield. The product was characterized by 1H NMR, 13C NMR, IR and HRMS. The purity was checked by HPLC.
  • 65
  • 1,2-O-dimyristoyl-sn-glycero-N,N-diisopropyl methylphosphoramidite [ No CAS ]
  • [ 14690-00-7 ]
  • C74H136O15P2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With 1H-tetrazole 8 l,2-O-dimyristoyl-.s7z-glycerol was reacted with ΛζΛ'-diisopropylmethylphosphonamidic chloride in the presence of ΛζN-diisopropylethylamine (DIPEA) in dichloromethane at room temperature to give 1,2- (9-dimyristoyl -5n-glycero-ΛζΛr-diisopropyl methylphosphoramidite which was subsequently reacted with 2-benzyloxy-l,3-propanediol, in the presence of l//-tetrazole, to provide a phosphite triester. In situ oxidation of the phosphite trimester, with m-chloroperbenzoic acid (mCPBA) at -40 0C, afforded 2- O-benzyl-l,3-bis-(l,2-O-dimyristoyl -5«-glycero-3-phosphoryl)glycerol dimethyl ester which was then purified on a silica gel column (hexane-ethyl acetate, 2:1-1:1) resulting in 2-O-benzyl-l,3-bis-( 1,2-0- dimyristoyl -sn-glycero-3-phosphoryl)glycerol dimethyl ester as a colorless oil with a 90% yield. Hydrogenolysis of 2-O-benzyl-l,3-bis-(l,2-O-dimyristoyl -5κ-glycero-3-ρhosphoryl)glycerol dimethyl ester, with H2/Pd-C in ethanol at 40 psi for 3 hours, furnished l,3-bis-(l,2-0-dimyristoyl-i'n-glycero-3- phosphoryl)glycerol dimethyl ester as a colorless oil with a 96% yield. The central hydroxyl functionality of l,3-bis-(l,2-0-dimyristoyl-5«-glycero-3-phosρhoryl)glycerol dimethyl ester (cardiolipin analogue) was reacted with succinic anhydride in the presence of triethylamine and 4-dimethylamino pyridine (DMAP) in 1 ,2-dichloroethane to provide 1 ,3-bis-( 1 ,2-O-dimyristoyl-572-glycero-3 -phosphoryl)-2-succinylglycerol dimethyl ester with a 78% yield. l,3-bis-(l,2-O-dimyristoyl-ir«-glycero-3-phosphoryl)-2-succinylglycerol dimethyl ester was coupled with 4-^-3 '-O-bis(tert-butoxycarbonyl)gemcitabine in the presence of N1N- dicyclohexyl carbodimide (DCC) and DMAP in dichloromethane at room temperature for 5 hours. This reaction was followed by purification on a silica gel column (hexane-ethyl acetate, 7:3-4: 1 and hexane:ethylacetate: methanol, 1:1:0.1) which afforded 4-iV-3'-0-di(tert-butoxycarbonyl)-5'-0-succinyl-[2- 0-l,3-bis-(l,2-0-dimyristoyl-src-glycero)-3-phosphoryl glycerol dimethyl ester] gemcitabine in a 72% yield. The protecting groups were removed using trifluororacetic acid (TFA) in dichloromethane at room temperature. The reaction solution was neutralized with 5% aqueous sodium bicarbonate at 0 0C, extracted with dichloromethane and concentrated. Purification of the crude compound on a silica gel column (methylene chloride-ethyl acetate, 9.8:0.2-9.6:0.4) afforded pure 5'-O-succinyl-[2-O-l,3-bis-(l,2- O- dimyristoyl -57z-glycero)-3-phosphorylglycerol dimethyl ester]gemcitabine as a viscous oil in a 50% yield. The product was characterized by 1H NMR. The purity was checked by HPLC.
  • 66
  • Myr-[G2]-PGLSA-acid [ No CAS ]
  • [ 14690-00-7 ]
  • 2-benzyI-1,3-di(Myr-[G2]-PGLSA)2-glycerol [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 16h; 81 0.85 g (0.62 mmol) of compound Myr-[G2]-PGLSA-acid was dissolved in 75 mL Of CH2Cl2 with 0.05 g (0.26 mmol) of 2-benzyl-glycerol, 0.08 g (0.26 mmol) of DPTS, and 0.16 g (0.77 mmol) of DCC. The reaction was stirred at RT for 16 hours. The DCU precipitate was filtered and the solution was evaporated. The residue was resuspended in 50 mL of ethanol, cooled to 0 0C for 6 hours and filtered. The precipitate was purified by column chromatography (20-50% EtOAc in hexanes) to yield 0.63 g of product (85% yield). Rf = 0.17 (30% EtOAc in hexanes). 1H NMR (CDCl3): δ 0.81-0.88 (t, 24H, -CH3), 1.17-1.34 (m, 160Η, myristic -CH2-), 1.52-1.63 (m, 16Η, C(KJ)-CH2-CH2-CH2-), 2.24-2.32 (t, 16H, C(O)-CH2-CH2-), 2.58-2.66 (m, 24H, succinic -CH2-CH2), 3.77-3.85 (m, 1Η, - CH2-CH-CH2-), 4.04-4.38 (m, 28H, -CH2-CH-CH2-), 4.59-4.65 (s, 2Η, benzyl -CH2-), 5.17-5.34 (m, 6Η, -CH2-CH-CH2-), 7.25-7.34 (m, 5H, aromatic CH) ppm. MALDI-MS: 2933.4 m/z (M+Na+) (theory: 2933.0 m/z (M+Na+)). Elemental analysis: C, 67.92%; Η, 9.79% (theory: C, 67.69%; Η, 9.77%). SEC: Mw = 4388, Mn = 4258, PDI = 1.03.
  • 67
  • (C5H5FeC5H3CH2N(CH3)2PdCl)2 [ No CAS ]
  • [ 14690-00-7 ]
  • 2-O-Benzyl-1-O-(2-dimethylaminomethylferrocenoyl)-sn-glycerol [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% With carbon monoxide In not given CO bubbled through soln. of Pd complex and 2-O-benzylglycerol in C6H6 or toluene during 4 h while stirred; treated with aq. NaHCO3, C6H6, org. layer dried, concd., chromd. (SiO2,MeCO2Et, hexane/Et3N, MeOH);
  • 68
  • [ 14690-00-7 ]
  • [ 124-63-0 ]
  • [ 114415-99-5 ]
YieldReaction ConditionsOperation in experiment
With triethylamine In dichloromethane at 0 - 20℃; for 2.5h; 13.3 A solution of 2-Benzyloxy-1 ,3-propanediol (20 mmol) in dry CH2CI2 (50 mL) is additioned with dry TEA (90 mmol) and then treated with methanesulfonyl chloride (65 mmol) at 0 °C for 30 min (dropwise added at 0 °C). The reaction mixture is stirred for 2 h at room temperature. The mixture is washed with 50 mM sodium bicarbonate (6-7 times with 300 mL), dried over magnesium sulfate and the solvent is evaporated under reduced pressure. The product is precipitated by adding of hexane and slowly evaporating CH2CI2 and the yellowish product is washed with hexane and dried.
  • 69
  • [ 60562-16-5 ]
  • [ 14690-00-7 ]
  • [ 15074-54-1 ]
  • [ 628722-33-8 ]
YieldReaction ConditionsOperation in experiment
72% Stage #1: 1,2-dimyristoyl-sn-glycerol; 2-chlorophenyl dichlorophosphate With pyridine In dichloromethane at 0 - 20℃; for 2.75h; Stage #2: 2-O-benzylglycerol In dichloromethane at 20℃; for 3h; 1.A To a solution of o-chlorophenyl dichlorophosphate (2.45 g, 9.98 mmol) and dry pyridine (4.39 mL, 54.28 mmol) in [CH2C12] (10 mL) was added dropwise a solution of [1,] [2-O-DIMYRISTOYL-SN-GLYCEROL] (5.00 g, 9.75 mmol) in [CH2CL2] (50 [ML)] at [0°C] over 45 min. After the reaction mixture was stirred at [0°C] for 1 h and at rt for 1 h, a solution [OF 2-BENZYLOXY-1,] 3-propanediol (0.71 g, 3.90 mmol) in CH2C12 (8 mL) was added dropwise. The reaction mixture was stirred at rt for 3 h. The organic solvent was removed in vacuo and the residue was partitioned between ethyl acetate (150 mL) and cold [0.] 5N HCl (100 mL). The organic phase was washed with water, brine, dried over anhydrous [NA2S04] and concentrated in vacuo. The obtained residue was purified by flash chromatography on silica gel using hexane/ethyl acetate (3: 1) to afford 4.37 g of fully protected cardiolipin as a colorless oil. The yield is 72 %. TLC (Hexane/EtOAc 3: 1) Rf = 0. 31 [;'HNMR] (500 MHz, CDC13) [8] 7.40-7. 08 (m, 13H, ArH), 5.22 (m, 2H, [RCOOCH),] 4.63 (m, 2H, [CH2PH),] 4.40-4. 06 (m, 12H, RCOOCH2, [POCK2),] 3.89 (m, [1H,] [BNOCH),] 2.26 (m, 8H,-CH2COO-), 1.57 (m, 8H, -CH2CH2COO-), 1.25 (br s, 80H, [CH2),] 0. [88] (t, J = 6.5, 12H, [CH3)] ; ESI-MS, [M/Z] (M+Na) + 1576.6.
  • 70
  • [ 60562-16-5 ]
  • [ 14690-00-7 ]
  • [ 86030-43-5 ]
  • [ 628722-39-4 ]
YieldReaction ConditionsOperation in experiment
90% Stage #1: 1,2-dimyristoyl-sn-glycerol; N,N-diisopropylmethylphosphonamidic chloride With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 2h; Stage #2: 2-O-benzylglycerol With 1H-tetrazole In dichloromethane; acetonitrile at 20℃; for 3h; Stage #3: With 3-chloro-benzenecarboperoxoic acid In dichloromethane; acetonitrile at -40 - 25℃; 4.A To a solution [OF N, N DIISOPROPYLMETHYLPHOSPHONAMIDIC] chloride (1.92 g, 9.22 mmol) and dry N, N-diisopropylethylamine (1.92 mL, 11.1 mmol) in [CH2CL2] (10 mL) was added dropwise a solution of 1, 2-O-dimyristoyl-sn-glycerol (4.61 g, 9.0 mmol) in CH2Cl2 (45 mL) at rt over 30 min. After the reaction mixture was stirred at rt for 1. [5] h, [LH-TETRAZOLE] of 3 wt% solution in acetonitrile (71.8 mL, [24. 3 MMOL)] was added. To this reaction mixture, a solution of 2-benzyloxy-1, 3-propanediol (0.66 g, 3.60 mmol) in [CH2CL2] (10 mL) was added dropwise. The reaction mixture was stirred at rt for 3 h. The reaction mixture was then cooled to-40 [C] and a solution of 77 % [M-CHLOROPEROXYBENZOIC] acid (2.64 g, 11.80 mmol) in [CH2C12] (10 mL) was added such that the temperature of the reaction mixture was kept below [0°C.] On warming to 25 [°C,] the mixture was transferred to a separating funnel and washed with 5 % [NAHC03] (2 X 50 mL), cold IN [HCL] [(2 X 15] mL), water, brine. The organic phase was dried over [NA2S04] and concentrated in vacuo to yield an oil residue. The residue was purified by flash chromatography on silica gel eluting with hexane/ethyl acetate (2: 1 to 1: 1) to afford 4. [38] g of fully protected cardiolipin as a colorless oil. The yield is 90 %. TLC (Hexane/EtOAc 1: 1) Rf = 0.16 [;'HNMR] (300 MHz, CDC13) [8] 7.35 (m, [5H,] ArH), 5.22 (m, 2H, [RCOOCH),] 4.67 (m, 2H, CH2Ph), 4.34-4. 06 (m, 12H, RCOOCH2, [POCK2),] 3.83 (m, 1H, BnOCH), 3.75 (dt, [JL = 11.] 4, J2 = 3.0, 6H, [POCH3),] 2.31 (m, [8H,-CH2COO-),] 1.59 (m, [8H,-CH2CH2COO-),] 1.25 (br s, 80H, CH2), 0. [88] (t, [J = 6.] 6,12H, [CH3).]
  • 71
  • [ 14690-00-7 ]
  • [ 36314-51-9 ]
  • [ 86030-43-5 ]
  • 2-O-benzyl-1.3-bis(1,2-O-dimyristyl-sn-glycero-3-phosphoryl)glycerol dimethyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% Stage #1: (R)-1,2-bis-tetradecyloxy propane-3-ol; N,N-diisopropylmethylphosphonamidic chloride With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.25h; Stage #2: 2-O-benzylglycerol With 1H-tetrazole In dichloromethane; acetonitrile at 20℃; for 3h; Stage #3: With 3-chloro-benzenecarboperoxoic acid In dichloromethane; acetonitrile at -40 - 25℃; 5.A To a stirred solution [OF N, N DIISOPROPYLMETHYLPHOSPHONAMIDIC] chloride (1.02 g, 5.15 mmol) and dry N,N-diisopropylethylamine (1.2 mL, 6.94 mmol) in [CH2CL2] (4 mL) was added dropwise a solution of 1, 2-O-dimyristyl-sn-glycerol (2.00 g, 4.13 mmol) in [CH2CL2] (20 mL) at rt over 15 min. After the reaction mixture was stirred at rt for 1.5 h, 1H-tetrazole of 3 wt% solution in acetonitrile [(31.] 0 mL, 10.5 mmol) was added. To this reaction mixture, a solution [OF 2-BENZYLOXY-1,] 3- propanediol (0.30 g, 1.65 mmol) in CH2Cl2 (5 mL) was added. The reaction mixture was stirred at rt for 3 h. The reaction mixture was then cooled to -40°C and a solution of 77 % [M-CHLOROPEROXYBENZOIC] acid (1.14 g, 6.6 mmol) in [CH2C12] (7 mL) was added. The mixture was gradually warmed to rt for 30 min, then transferred to a separating funnel and washed with 5 % [NAHC03] (2 X 30 mL), 1N HCl (2 X 20 mL), water, brine. The organic phase was dried over [NA2S04] and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a gradient of hexane/ethyl acetate (1: 0 to 1: 1) to afford 1.69 g of 2-O-benzyl-1, 3-bis [(1,] [2-O-] dimyristyl-sn-glycero-3-phosphoryl) glycerol dimethyl ester. The yield is 79 %. TLC (Hexane/EtOAc 1: 1) [RF] = 0.24. HNMR (300 MHz, [CDC13)] 8 7.35-7. 29 (m, [SH,] ArH), 4.68 (m, 2H, CH2Ph), 4.26-4. 02 (m, 8H, [POCK2),] 3.86 (m, 2H, ROCH), 3.75 (d, Jl [=] 12.0, 6H, [POCH3),] 3.61-3. 38 (m, [13H,-CH2OCH2-,-CH20CH-,] [BNOCH),] 1.54 (m, [8H,-CH2CH20-),] 1.29 (m, 88H, [CH2),] 0.88 (t, [J =] 6.7, 12H, [CH3).]
  • 72
  • [ 28874-52-4 ]
  • [ 14690-00-7 ]
  • 2-O-benzyl-1,3-bis(1,2-O-dimyristoyl-sn-glycero-3-phosphoryl)glycerol diammonium salt [ No CAS ]
YieldReaction ConditionsOperation in experiment
4% Stage #1: L-α-dimyristoylphosphatidic acid With pyridine; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 0.0833333h; Stage #2: 2-O-benzylglycerol In dichloromethane at 20℃; for 24h; 6.A To a stirred solution [OF N, N'-DICYCLOHEXYLCARBODIMIDE] (265 mg, 1.28 mmol) in pyridine (2 [ML)] was added dropwise 1, [2-O-DIMYRISTOYL-SN-GLYCERO-3-] phosphatidic acid (281 mg, 0.47 mmol) in anhydrous [CH2C12] (3 mL). The solution was stirred for 5 min at rt, and then 2-benzyloxy-1, 3-propanediol (0.71 g, 3.90 mmol) in [CH2CI2] (8 mL) was added and the stirring continued at rt for 24 h. The reaction was filtered and washed with [CHZCIZ.] The filtrate was concentrated and co- evaporated with toluene to remove traces of pyridine. To the residue, [CH2CL2] (15 mL) was added and the mixture was stored in the freezer overnight. The white precipitation was removed by filtration. The filtrate was concentrated in vacuo and purified on silica gel column eluting with [CHC13/MEOH/NH40H] (65: 15: 1). Yield 13 mg (4 %). TLC [(CHC13/MEOH/NH40H] 65: 25: 5) Rf = 0.64. The TLC was identical with the authentic sample prepared according to the method described in Example [IB.]
  • 73
  • [ 50-00-0 ]
  • [ 14690-00-7 ]
  • [ 41128-92-1 ]
YieldReaction ConditionsOperation in experiment
78% With boron trifluoride diethyl etherate In ethyl acetate at 23℃; for 4h; Inert atmosphere;
78% With boron trifluoride diethyl etherate In ethyl acetate at 23℃; for 4h; 17 Example 171,3-Dioxan-5-ol (8h). To a mixture of 17 (100 mg, 0.55 mmol) and paraformaldehyde (17 mg, 0.55 mmol) in EtOAc (10 mL), boron trifluoride etherate (70 μL, 0.55 mmol) was added and the reaction mixture was stirred at 23° C. for 4 h. The organic phase was washed with a saturated solution of NaHCO3, dried and the solvent was removed. The residue was purified by flash-chromatography eluting with a 1:4 mixture of EtOAc and hexanes to afford 84 mg (78%) of O-benzyl-1,3-dioxan-5-ol as a colourless oil. The above compound was dissolved in EtOAc (3 mL), Pd/C was added and the resulting suspension was stirred at rt under a hydrogen atmosphere. After 12 h, the catalyst was filtered off, the filtrate was evaporated in vacuo and the residue (39 mg, 100%) was used in the next step without further purification: 1H NMR (CDCl3) δ 4.93 (d, J=6.3 Hz, 1H), 4.76 (d, J=6.3 Hz, 1H), 3.94-3.84 (m, 4H), 3.64-3.61 (m, 1H), 2.78 (bs, 1H). 13C NMR (CDCl3) δ 94.0, 71.7, 64.1.
  • 74
  • [ 34604-52-9 ]
  • [ 14690-00-7 ]
  • [ 1067244-55-6 ]
YieldReaction ConditionsOperation in experiment
19% With sodium hydride In tetrahydrofuran for 20h; Reflux; Inert atmosphere;
19% With sodium hydride In tetrahydrofuran; mineral oil for 20h; Reflux; 18 Example 18O-Benzyl-3,6,9-trioxacyclodecan-1-ol (18). To a refluxing suspension of sodium hydride (60% in mineral oil, pre-washed with hexane, 84 mg, 2.1 mmol) in dry THF (5 mL), a solution of 17 (182 mg, 1.0 mmol) and di(ethyleneglycol)dimethanesulfonate (260 mg, 1.0 mmol) in dry THF (5 mL) was added dropwise. The resulting mixture was heated under reflux for 20 h, afterward was cooled to 23° C. and H2O (2 mL) was added. The solvent was removed and the aqueous phase was extracted with CHCl3. The organic extracts were washed several times with water, dried (Na2SO4) and evaporated. The residue was purified by flash-chromatography (2:3 CH2Cl2/EtOAc) to afford 49 mg (19%) of 18 as a colourless oil: 1H NMR (CDCl3) δ 7.36-7.26 (m, 5H), 4.66 (s, 2H), 3.75-3.57 (m, 13H); MS (ESI) m/z 275 [M+Na]+.
  • 75
  • [ 14690-00-7 ]
  • [ 80322-82-3 ]
  • [ 1067244-54-5 ]
YieldReaction ConditionsOperation in experiment
29% With sodium hydride In tetrahydrofuran Reflux; Inert atmosphere;
  • 76
  • 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranosyl chloride [ No CAS ]
  • [ 14690-00-7 ]
  • 1-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-glucopyranosyl)-2-O-benzylglycerol [ No CAS ]
YieldReaction ConditionsOperation in experiment
With zinc(II) chloride In dichloromethane Reflux; Molecular sieve; 3 Intermediate 2: 1 -0-(2-acetamido-3,4,6-tri-0-acetyl-2-deoxy-a-D-qlucopyranosyl)-2-0- benzyl-qlvcerol; The compound of Intermediate 1 (8 g) was weighed into a 3-necked 500 ml round- bottomed flask fitted with a magnetic stirrer, condenser with drying tube and a thermometer. The compound was dissolved in CH2CI2 (250 mL) and molecular sieves (4 A, 2g), 2-O-benzyl-glycerol (4.8g) and ZnCI2 (1.8g) were added. The solution was refluxed overnight and cooled to room temperature. The reaction mixture wad washed with NaHC03 (Sat. aq., 2x200 mL) and water (200 mL). The organic phase was dried with Na2S04, filtered and evaporated. The product was purified by column chromatography. The structure of Intermediate 2 was confirmed by H-NMR, 3C-NMR and infusion- electrospray-MS in positive mode (see Figs. 8-15).
  • 77
  • [ 14690-00-7 ]
  • [ 41680-34-6 ]
  • [ 1356016-72-2 ]
YieldReaction ConditionsOperation in experiment
9% To solution of oxalyl chloride (0.6 mL, 6.87 mmol) in anhydrous dichloromethane (15 mL), cooled at -78 C., was added, dropwise, a solution of anhydrous dimethyl sulfoxide (1.2 mL, 16.5 mmol) in dichloromethane (2 mL) and the resulting mixture was stirred for 10 minutes at -78 C. A solution of 2-benzyloxy-1,3-propanediol (0.5 g, 2.75 mmol) in dichloromethane (2 mL) was then added dropwise at -78 C. and the reaction mixture was stirred for 15 minutes. Triethylamine (4.6 mL, 33 mmol) was then added dropwise at -78 C. and the resulting mixture was stirred for 1 hour. The cold bath was removed and an aqueous solution of hydrochloric acid (6 M, 6 mL, 36 mmol) was added, followed by <strong>[41680-34-6]5-amino-1H-pyrazole-4-carboxylic acid</strong> (0.35 g, 2.75 mmol) and the reaction mixture was heated at 70 C. for 1 hour. The solid formed was collected by filtration, washed with water and dried under vacuum. The solid residue (0.53 g) was then washed with dichloromethane to give 65 mg (9% yield) of 6-benzyloxy-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid. MS=270 [M+H]+.
  • 78
  • methyl (Z)-10-(2-hexylcyclopropan-1-yl)decanoate [ No CAS ]
  • [ 14690-00-7 ]
  • 1-O-(cis-11',12'-methylene-octadecanoyl)-2-O-benzylglycerol [ No CAS ]
YieldReaction ConditionsOperation in experiment
48 mg With Pseudomonas cepacia lipase In chloroform at 30℃; for 144h; Enzymatic reaction; 1-O-(cis-11',12'-methylene-octadecanoyl)-2-O-benzylglycerol (11) A solution of 10a (40 mg) in CHCl3 (10 mL) was added to the mixture of 2-O-benzylglycerol (400 mg) and lipase PS (200 mg). After being stirred at 30°C for 6 d, the reaction mixture was concentrated under reduced pressure. The resulting residue was purified by reversed-phase HPLC (H2O-MeOH (5:95)) to yield 11 (48 mg) as a colorless oil; [a] -6.8,(c 0.25, CHCl3); 1H NMR (CDCl3, 300 MHz) d 7.38-7.26 (5 H, m, Ph), 4.72 (1 H, d, J = 11.7 Hz, PhCH2O), 4.60 (1 H, d, J = 11.7 Hz, PhCH2O), 4.23 (2 H, d, J = 4.8 Hz, H-1), 3.70 (3 H, m, H-2, H-3), 3.63 (1 H, m, H-3), 2.32 (2 H, dd, J = 7.8, 7.5 Hz, H-2'), 2.10 (1 H, br t, OH), 1.61 (2 H, t, J = 7.2 Hz, H-3'), 1.32-1.27 (22 H, m), 1.08 (2 H, m), 0.88 (3 H, t, J = 6.6 Hz, H-18'), 0.64 (2 H, m, H-11', H-12'), 0.57 (1 H, ddd, J = 8.6, 8.6, 4.3, H-19'), -0.34 (1 H, dd, J = 9.5, 4.7 Hz, H-19').
  • 79
  • [ 14690-00-7 ]
  • [ 112-67-4 ]
  • [ 76163-48-9 ]
YieldReaction ConditionsOperation in experiment
99% With pyridine In dichloromethane at 0 - 20℃; for 20h; Inert atmosphere;
  • 80
  • [ 558-13-4 ]
  • [ 14690-00-7 ]
  • [ 35995-55-2 ]
YieldReaction ConditionsOperation in experiment
With triphenylphosphine 112.1 Step 1: Step 1: (((1,3-dibromopropan-2-yl)oxy)methyl)benzene To a suspension of -2-(benzyloxy)propane-1,3-diol (1 g, 5.49 mmol) in DCM (27.4 ml) at 0° C., was added triphenylphosphine (7.05 g, 26.9 mmol) and carbon tetrabromide (8.74 g, 26.3 mmol). The reaction mixture was brought to ambient temperature and stirred for 16 hours. The reaction mixture was concentrated and the crude solid was rinsed with heptanes. The filtrate was collected and concentrated in vacuo to provide the title compound (0.85 g, 2.76 mmol) as a colorless oil.
  • 81
  • [ 14690-00-7 ]
  • C21H20F3N5O2 [ No CAS ]
  • C31H32F3N5O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride at 20℃; 40-2 General procedure: (2) Compound 3 (157 mg) was dissolved in methanol (6 mL) and to this was added 1N hydrochloric acid (2 mL), and the mixture was stirred at room temperature overnight. The reaction solution was concentrated under reduced pressure, and an aqueous saturated sodium hydrogen carbonate solution, ethyl acetate and tetrahydrofuran were added to the obtained residue under ice cooling to carry out a liquid separation. The organic layer was separated, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. After the obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 100:0 to 80:20), isopropyl ether and n-hexane were added, and the solid was collected by filtration to obtain Compound 4 (75 mg) and Compound 5 (20 mg). A treatment was carried out in a manner similar to the Example 40-1 to obtain a compound of Example 40-2in Table 20 below.
  • 82
  • [ 14690-00-7 ]
  • [ 74-88-4 ]
  • (((1,3-dimethoxypropan-2-yl)oxy)methyl)benzene [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium hydride 4.1 Step-1 : Preparation of (((l,3-dimethoxypropan-2-yl)oxy)methyl)benzene (Compound 13). 2-(Benzyloxy)propane-l,3-diol is reacted with methyl iodide (2 eq) in the presence of NaH (2.2 eq) as base, to afford (((l,3-dimethoxypropan-2-yl)oxy)methyl)benzene (Compound 13).
  • 83
  • [ 887144-94-7 ]
  • [ 14690-00-7 ]
  • 2-(benzyloxy)-3-(trifluoromethoxy)propan-1-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
58% With bis((1,1,1-trifluoro-N-(trifluoromethyl)sulfonyl)methylsulfonamido)zinc In chloroform at 30 - 32℃; for 20h; Inert atmosphere; 7.1 Step 1 : Preparation of 2-(benzyloxy)-3-(trifluoromethoxy)propan-l-ol (Compound 2-(Benzyloxy)propan-l,3-diol (25 g, 137 mmol), l-trifluoromethyl-l,2-benziodoxol- 3(lH)-one (4.34 g, 13.7 mmol) and bis( 1,1,1 -trifluoro-N- (trifluoromethyl)sulfonyl)methylsulfonamido)zinc (4.29 g, 6.85 mmol) were added to a round bottom flask containing 25 mL of chloroform. The reaction mixture was stired at 30-32 °C for 20 hours under nitrogen atmosphere. The reaction was monitored by 19F NMR. After completion of the reaction, the mixture was concentrated and the crude product obtained was purified by column chromatography (using ethyl acetate/hexane as eluant) giving 2- (benzyl oxy)-3 -(trifluoromethoxy)propan- 1 -ol (Compound 28) (2.0 g, 58% yield).
  • 84
  • [ 14690-00-7 ]
  • [ 76-83-5 ]
  • [ 96270-18-7 ]
YieldReaction ConditionsOperation in experiment
With triethylamine In dichloromethane 7A.1 Step- 1 : Preparation of 2-(benzyloxy)-3 -(trityloxy)propan- 1 -ol (Compound 33). 2-(Benzyloxy)propane-l,3-diol is reacted with 0.7 eq of trityl chloride in DCM as solvent and triethylamine (1 eq) as base. After completion of reaction, the crude product is purified by column chromatography to afford 2-(benzyloxy)-3-(trityloxy)propan-l-ol (Compound 33).
  • 85
  • [ 14690-00-7 ]
  • [ 95257-22-0 ]
YieldReaction ConditionsOperation in experiment
85.52% Stage #1: 2-O-benzylglycerol With n-butyllithium In tetrahydrofuran at 0℃; for 0.5h; Stage #2: With p-toluenesulfonyl chloride In tetrahydrofuran at 0℃; for 1h; Synthesis of 1-5 1-4 (127. 93g, 702. 06mmol) placed in a reaction flask was added 700mlTHF dissolution , the temperature control0 degrees butyllithium (280. 83ml, 1. Oeq), Bi drops stirred 30min, then 0 degrees dropping TsCl (133. 57g,1. Oeq), Bi dropping reaction lh, then around 0 degrees and then butyllithium (280. 83ml, 1. Oeq), addition is complete , warm to backFlow reactor overnight . The next day , TLC showed the reaction was complete , poured into water , and extracted three times with ethyl acetate , washed with water and saturated brineOnce dried and concentrated under reduced pressure distillation colorless liquid 1-598. 59g, yield 85.52%;
  • 86
  • [ 14690-00-7 ]
  • C7H11NO2 [ No CAS ]
  • C17H23NO4 [ No CAS ]
  • C17H23NO4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 6% 2: 6% With pyridinium p-toluenesulfonate In toluene at 90℃; for 6h; 9.3 Step 3 Synthesis of compound a60 In toluene (1 ml) of the aldehyde, 2- (benzyloxy) propane-1,3-diol (54 mg, 0.298 mmol) and pyridinium p-toluenesulfonate (2.5mg, 9.9μmol) was added, 90 ° C. in and the mixture was stirred for 6 hours. The reaction was concentrated, residue was purified by preparative HPLC - was purified by (0.1% formic acid-containing acetonitrile-water), compound a60 (3.8mg, 6% yield) and its cis isomer (4.0 mg, 6% yield).
1: 6% 2: 6% With pyridinium p-toluenesulfonate In toluene at 90℃; for 6h; 22.3 Step 3 Preparation of Compound c60 2- (benzyloxy) propane-1,3-diol (54mg, 0.298mmol) and pyridinium paratoluene sulfonate (2.5mg, 9.9µmol) were added to the toluene (1ml) solution of the aldehyde, and it was stirred at 90°C for 6 hours. The reaction solution was concentrated, and the residue was purified by prep HPLC (0.1% formic acid-containing acetonitrile-water) to afford Compound c60 (3.8mg, 6% yield) and its cis isomer (4.0mg, 6% yield). 1H NMR (CDCl3)δ: 1.23 (d, J = 8.4 Hz, 3H), 1.95 (s, 3H), 3.49 (dd, J = 10.8, 10.8 Hz, 2H), 3.67 (m, 1H), 3.49 (dd, J = 4.8, 10.8 Hz, 2H), 4.56 (s, 2H), 4.62 (m, 1H), 4.86 (d, J = 4.4 Hz, 1H), 5.32 (d, J = 8.4 Hz, 1H), 5.59 (ddd, J =1.6, 4.4, 15.6 Hz, 1H) 5.93 (dd, J = 5.2, 15.6 Hz, 1H), 7.27-7.37 (m, 5H). Cis isomer;1 H NMR (CDCl3)δ : 1.24 (d, J = 6.8 Hz, 3H), 1.96 (s, 3H), 3.25 (s, 1H), 3.87 (d, J = 12.0 Hz, 2H), 4.23 (d, J = 12.0 Hz, 2H), 4.64 (m, 1H), 4.67 (s, 2H), 5.02 (d, J = 4.8 Hz, 1H), 5.36 (d, J = 7.2 Hz, 1H), 5.69 (ddd, J =1.6, 4.4, 16.0 Hz, 1H) 5.98 (dd, J = 4.8, 16.0 Hz, 1H), 7.27-7.39 (m, 5H).
  • 87
  • [ 14690-00-7 ]
  • C7H11NO2 [ No CAS ]
  • C10H19NO4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
2.6 mg Stage #1: 2-O-benzylglycerol; C7H11NO2 With pyridinium p-toluenesulfonate In toluene at 90℃; for 6h; Stage #2: With hydrogen; palladium(II) hydroxide In methanol for 5h; 22.4 Step 4 Preparation of Compound c61 2- (benzyloxy) propane-1,3-diol (54mg, 0.298mmol) and pyridinium paratoluene sulfonate (2.5mg, 9.9µmol) were added to the toluene (1ml) solution of the aldehyde, and it was stirred at 90°C for 6 hours. The reaction solution was concentrated, and the residue was purified by prep HPLC (0.1% formic acid-containing acetonitrile-water) to afford Compound c60 (3.8mg, 6% yield) and its cis isomer (4.0mg, 6% yield). 1H NMR (CDCl3)δ: 1.23 (d, J = 8.4 Hz, 3H), 1.95 (s, 3H), 3.49 (dd, J = 10.8, 10.8 Hz, 2H), 3.67 (m, 1H), 3.49 (dd, J = 4.8, 10.8 Hz, 2H), 4.56 (s, 2H), 4.62 (m, 1H), 4.86 (d, J = 4.4 Hz, 1H), 5.32 (d, J = 8.4 Hz, 1H), 5.59 (ddd, J =1.6, 4.4, 15.6 Hz, 1H) 5.93 (dd, J = 5.2, 15.6 Hz, 1H), 7.27-7.37 (m, 5H). Cis isomer;1 H NMR (CDCl3)δ : 1.24 (d, J = 6.8 Hz, 3H), 1.96 (s, 3H), 3.25 (s, 1H), 3.87 (d, J = 12.0 Hz, 2H), 4.23 (d, J = 12.0 Hz, 2H), 4.64 (m, 1H), 4.67 (s, 2H), 5.02 (d, J = 4.8 Hz, 1H), 5.36 (d, J = 7.2 Hz, 1H), 5.69 (ddd, J =1.6, 4.4, 16.0 Hz, 1H) 5.98 (dd, J = 4.8, 16.0 Hz, 1H), 7.27-7.39 (m, 5H).Step 4 Preparation of Compound c61 (0541) Compound c60 (4.0mg, 0.012mmol) was dissolved in methanol (1mL), and palladium hydroxide (1mg, 0.16mmol) was added thereto. The reaction mixture was stirred under hydrogen atmosphere for 5 hours. The reaction solution was filtered, and the filtrate was concentrated under reduced pressure to afford Compound c61 (2.6mg, 100% yield) as a crude product. 1H NMR (CDCl3) δ: 1.13 (d, J = 6.8 Hz, 3H), 1.45-1.68 (m, 4H), 1.95 (s, 3H), 3.67 (dd, J = 10.8, 10.8 Hz, 2H), 3.67 (m, 1H), 3.88 (m, 1H), 3.97 (m, 1H), 4.16 (dd, J = 4.8, 10.8 Hz, 2H), 4.44 (dd, J = 4.8, 4.8 Hz, 1H), 5.31 (br.s, 1H).
  • 88
  • [ 14690-00-7 ]
  • [ 57678-42-9 ]
  • C19H23NO3 [ No CAS ]
  • C19H23NO3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 138 mg 2: 50 mg With camphor-10-sulfonic acid In chloroform at 20℃; for 2h; Molecular sieve; Inert atmosphere; Overall yield = 91 %;
  • 89
  • C19H23NO3 [ No CAS ]
  • [ 14690-00-7 ]
YieldReaction ConditionsOperation in experiment
81% In methanol for 0.5h; UV-irradiation;
  • 90
  • [ 619-22-7 ]
  • [ 14690-00-7 ]
  • 91
  • [ 14690-00-7 ]
  • C14H15N3O [ No CAS ]
  • C24H27N3O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
18.5% With toluene-4-sulfonic acid In tetrahydrofuran at 120℃; for 24h; Microwave irradiation; 192 Synthesis of compound 192.7 Synthesis of compound 192.7. To a solution of 192.6 (4.5 g, 18.67 mmol, leq) and 192.4 (23.65 g, 13 Ommol, 7eq) in THF was added trimethylorthoformate (4.94 g, 46.7 mmol, 2.5eq) and p-TsOH (1.41 g, 74.7 mmol, 0.4 eq). The reaction was heated to reflux for 24 h. Upon completion of reaction, mixture was poured slowly into water and extracted with EtOAc. Combined organic layers was washed with 5% NaHCC , dried over Na2S04 and concentrated under reduced pressure to get crude which was purified by column chromatography to furnish 192.7 (1.4 g, 18.5%). MS(ES): m/z 406.21 [M+H]+.
  • 92
  • [ 111-25-1 ]
  • [ 14690-00-7 ]
  • (((1,3-bis(hexyloxy)propan-2-yl)oxy)methyl)benzene [ No CAS ]
YieldReaction ConditionsOperation in experiment
43% Stage #1: 2-O-benzylglycerol With sodium hydride In tetrahydrofuran at 40℃; for 2h; Inert atmosphere; Stage #2: 1-bromo-hexane With potassium iodide In tetrahydrofuran; N,N-dimethyl-formamide for 16h; Reflux; 1.XX83 (((l,3-Bis(hexyloxy)propan-2-yl) xy)methyl)benzene To a slurry of NaH (1.76 g, 43.9 mmol) in THF (40 mL) under N2 was added 2- (benzyloxy)propane-l,3-diol (2 g, 10.98 mmol) and the mixture was allowed to stir at 40 °C for 2 h. After this time 1 -bromohexane (4.35 g, 26.34 mmol) in DMF (2ml) and a catalytic amount of KI were added. The reaction was refluxed for 16 h. Solvents were evaporated under vacuum. The residue was diluted with EtOAc and washed with sat. NaHCC , followed by brine. The organic layer was separated, dried over Na2SC>4, filtered, and evaporated under vacuum. The residue was purified by silica gel chromatography with (0-40%) EtOAc in hexanes to obtain (((l,3-bis(hexyloxy)propan-2-yl)oxy)methyl)benzene (1.7 g, 4.75 mmol, 43%). l NMR (300 MHz, CDCI3) δ: ppm 7.34 (m, 5H); 4.73 (s, 2H); 3.75 (m, 1H); 3.61-3.40 (m, 8H); 1.59 (m, 4H); 1.32 (m, 12H); 0.91 (m, 6H).
43% Stage #1: 2-O-benzylglycerol With sodium hydride In tetrahydrofuran at 40℃; for 2h; Reflux; Inert atmosphere; Stage #2: 1-bromo-hexane With potassium iodide In tetrahydrofuran; N,N-dimethyl-formamide for 16h; Reflux; 1.EO (((l,3-bis(hexyloxy)propan-2-yl)oxy)methyl)benzene [00261] To a slurry of NaH (1.76 g, 43.9 mmol) in THF (40 mL) under N2 was added 2- (benzyloxy)propane-l,3-diol (2 g, 10.98 mmol) and the mixture was allowed to stir at 40 °C for 2 h. After this time 1-bromohexane (4.35 g, 26.34 mmol) in DMF (2ml) and a catalytic amount of KI were added. The reaction was refluxed for 16 h. Solvents were evaporated under vacuum. The residue was diluted with EtOAc and washed with sat. NaHCC, followed by brine. The organic layer was separated, dried over Na2S04, filtered, and evaporated under vacuum. The residue was purified by silica gel chromatography with (0-40%) EtOAc in hexanes to obtain (((l,3-bis(hexyloxy)propan-2-yl)oxy)methyl)benzene (1.7 g, 4.75 mmol, 43%). 1H NMR (300 MHz, CDCb) δ: ppm 7.34 (m, 5H); 4.73 (s, 2H); 3.75 (m, 1H); 3.61-3.40 (m, 8H); 1.59 (m, 4H); 1.32 (m, 12H); 0.91 (m, 6H).
  • 93
  • [ 14690-00-7 ]
  • [ 18496-54-3 ]
  • 2-(benzyloxy)-3-hydroxypropyl 4-phenylbutanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
58.7 g With pyridine; In dichloromethane; at 0℃; for 0.5h; Synthesis of 2-(Benzyloxy)-3-hydroxypropyl 4-phenylbutanoate (7): To a stirred solution of 2-(benzyloxy)propane-l ,3-diol 4 (58 g, 0.318 mol) in DCM (800 mL), pyridine (75.5 g, 0.955 mol) was added and cooled to 0C. To this, a solution of <strong>[18496-54-3]4-phenylbutanoyl chloride</strong> 6 (63.95 g, 0.35 mol) in DCM (100 mL) was added and stirred the mixture at 0C for 30 min. After completion of reaction on TLC, reaction mixture was diluted with DCM (500 mL) and washed with water (2 x 2 Lt) and brine (2 Lt). The organic layer was dried over sodium sulfate and concentrated under vacuum. The resulting crude was purified by column chromatography on silica gel (100-200 mesh) using 28% EtOAc-hexane as an eluent to afford 7 (58.7 g, 56%) as a colourless liquid. 1H NMR (400 MHz, DMSO-d6): δ 7.31-7.26 (m, 7H), 7.18-7.16 (m, 3H), 4.79 (m, 1H), 4.58 (m, 2H), 4.24 (m, 1H), 4.04 (m, 1H), 3.58 (m, 1H), 3.49 (m, 2H), 2.58 (m, 2H), 2.29 (m, 2H), 1.81 (m, 2H).
  • 94
  • [ 14690-00-7 ]
  • [ 682-30-4 ]
  • tetraethyl [(2-benzyloxypropane-1,3-diyl)bis(oxy)]bis(ethylene)}bis(phosphonate) [ No CAS ]
YieldReaction ConditionsOperation in experiment
78% With caesium carbonate In <i>tert</i>-butyl alcohol at 20℃; for 48h; Inert atmosphere; 4 4.5. Tetraethyl [(2-benzyloxypropane-1,3-diyl)bis(oxy)]bis(ethylene)}bis(phosphonate) (6) Diol 5 (12.1 g, 66 mmol) and cesium carbonate (21.5 g,66 mmol) were placed into 250 ml reaction flask. Dry tert-Butylalcohol (70 ml) was added, the flask was sealed with a septum and filled with argon. Diethyl vinylphosphonate (28 ml, 185 mmol,2.8 eq.) was added into the flask and the mixture was vigorously stirred for two days. The reaction mixture was diluted with water and extracted with EtOAc (3 200 mL). The organic phase was collected,washed with water (2 200 ml), followed by brine(1 200 ml) and dried over MgSO4. The solution was filtered and evaporated in vacuo. Crude product was purified by flash chromatography(silica gel; eluent hexan:EtOAc [6:4]/MeOH gradient0-10%) to obtained 26.2 g (78%) of 6 as colourless oil. Pure product was used in the next reaction step without additional characterisation.MS (ESI+) m/z = 511.3 [M+H]+
  • 95
  • [ 14690-00-7 ]
  • [ 79099-07-3 ]
  • C20H29NO5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
66% With toluene-4-sulfonic acid In dichloromethane at 20℃; for 3h; 1.1.1 1.1 Synthesis of compound III 1.0 g (5.0 mmol) of Compound II, 1.0 g (5.5 mmol) of 2-benzyloxy-1,3-propanediol, 190 mg (1.7 mmol) of orthoformate, 1.1 g of orthoformate was dissolved in 100 ml of anhydrous dichloromethane and reacted at room temperature. After 3 h, saturated solution of sodium bicarbonate was added to adjust PH to neutrality. The organic phase is washed with water, then brine, dried over anhydrous sodium sulfate and concentrated. Petroleum ether / ethyl acetate = 5/1 column chromatography to give compound III as a colorless oily liquid, 1.2 g, yield 66%.
  • 96
  • [ 14690-00-7 ]
  • [ 108-88-3 ]
YieldReaction ConditionsOperation in experiment
83% With methanol; toluene-4-sulfonic acid at 25℃; for 9h; Inert atmosphere; Sealed tube; UV-irradiation; 19; 23 Example 20 A glass reaction vessel was charged with 18.6 mg of Catalyst B,110.2 mg (1.0 mmol)Of benzyl alcohol,13.2 mg (0.06 mmol) TsOH.H 2 0,30 mL dehydrated methanol,And a magnetic stirrer.Then, an argon gas is introduced into the sealed reaction system,Under the condition of 25 ° C.,While stirring the reaction system (rotational speed of the magnetic stirrer: about 600 rpm)Ultraviolet rays were irradiated for 12 hours to obtain toluene. The yield was 88% (see Table 4).
  • 97
  • [ 14690-00-7 ]
  • [ 65-85-0 ]
YieldReaction ConditionsOperation in experiment
37% With oxygen; sodium t-butanolate In dichloromethane at 60℃; for 18h;
  • 98
  • [ 14690-00-7 ]
  • [ 30379-55-6 ]
  • [ 65-85-0 ]
YieldReaction ConditionsOperation in experiment
1: 68% 2: 22% With oxygen; sodium t-butanolate In toluene at 60℃; for 18h;
  • 99
  • [ 56-81-5 ]
  • [ 100-51-6 ]
  • 3-benzyloxypropan-1,2-diol [ No CAS ]
  • [ 14690-00-7 ]
  • [ 6972-79-8 ]
YieldReaction ConditionsOperation in experiment
With sulfonated acidic carbon In neat liquid at 120℃; for 6h; Inert atmosphere; 3. Catalytic test General procedure: The catalytic performance of the acidic carbon was studied in the etherification of commercial glycerol (Gly, Biopack 99.5 %) and crude glycerol (GlyC) with benzyl alcohol (BA, Anedra analytic reagent). The reaction was carried out in a batch glass reactor (100 mL) without solvent, under continuous stirring and N2 atmosphere. In the catalytic tests, the influence of different operational variables was studied: the Gly:BA molar ratio (3:1, 1:1 and 1:3), the mass of catalyst in relation to the mass of glycerol employed (2.5, 5 and 10 wt.%) and different temperatures (80, 100 and 120 °C). Stirring was fixed for all experiments at 1200 rpm to avoid external diffusion limitations. After 360 min of reaction, a sample was taken, filtered and analysed by gas chromatography. The conversion was calculated from chromatographic data obtained using a Varian CG-3800 gas chromatograph equipped with a capillary column CP WAX 52 CB (30 m; 0.53 mm d.i.; 1.0 μm d.f.) and an FID detector. Butyl alcohol was used as internal standard for the calibration curve and ethanol as solvent. Commercial standards of (±) 3-benzyloxy-1,2-propanediol and 1,3-dibenzyloxy-2- propanol were utilized to obtain the corresponding response factors. GC/MS was employed for the identification of the products using a Shimadzu QP2010 Ultra gas chromatograph with an SH-Rtx-5Sil MS (30 m; 0.25 mm d.i.; 0.25 μm d.f) column.
  • 100
  • [ 56-81-5 ]
  • [ 100-51-6 ]
  • 3-benzyloxypropan-1,2-diol [ No CAS ]
  • [ 103-50-4 ]
  • [ 14690-00-7 ]
  • [ 6972-79-8 ]
YieldReaction ConditionsOperation in experiment
With sulfonated acidic carbon In neat liquid at 120℃; for 6h; Inert atmosphere; 3. Catalytic test The catalytic performance of the acidic carbon was studied in the etherification of commercial glycerol (Gly, Biopack 99.5 %) and crude glycerol (GlyC) with benzyl alcohol (BA, Anedra analytic reagent). The reaction was carried out in a batch glass reactor (100 mL) without solvent, under continuous stirring and N2 atmosphere. In the catalytic tests, the influence of different operational variables was studied: the Gly:BA molar ratio (3:1, 1:1 and 1:3), the mass of catalyst in relation to the mass of glycerol employed (2.5, 5 and 10 wt.%) and different temperatures (80, 100 and 120 °C). Stirring was fixed for all experiments at 1200 rpm to avoid external diffusion limitations. After 360 min of reaction, a sample was taken, filtered and analysed by gas chromatography. The conversion was calculated from chromatographic data obtained using a Varian CG-3800 gas chromatograph equipped with a capillary column CP WAX 52 CB (30 m; 0.53 mm d.i.; 1.0 μm d.f.) and an FID detector. Butyl alcohol was used as internal standard for the calibration curve and ethanol as solvent. Commercial standards of (±) 3-benzyloxy-1,2-propanediol and 1,3-dibenzyloxy-2- propanol were utilized to obtain the corresponding response factors. GC/MS was employed for the identification of the products using a Shimadzu QP2010 Ultra gas chromatograph with an SH-Rtx-5Sil MS (30 m; 0.25 mm d.i.; 0.25 μm d.f) column.
Recommend Products
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 14690-00-7 ]

Aryls

Chemical Structure| 58530-76-0

[ 58530-76-0 ]

(R)-2,3-Bis(benzyloxy)propan-1-ol

Similarity: 0.96

Chemical Structure| 20196-71-8

[ 20196-71-8 ]

(S)-2,3-Bis(benzyloxy)propan-1-ol

Similarity: 0.96

Chemical Structure| 70448-03-2

[ 70448-03-2 ]

2-(Benzyloxy)propan-1-ol

Similarity: 0.96

Chemical Structure| 33106-64-8

[ 33106-64-8 ]

(S)-2-(Benzyloxy)propan-1-ol

Similarity: 0.96

Chemical Structure| 17325-85-8

[ 17325-85-8 ]

(S)-3-(Benzyloxy)propane-1,2-diol

Similarity: 0.93

Ethers

Chemical Structure| 58530-76-0

[ 58530-76-0 ]

(R)-2,3-Bis(benzyloxy)propan-1-ol

Similarity: 0.96

Chemical Structure| 20196-71-8

[ 20196-71-8 ]

(S)-2,3-Bis(benzyloxy)propan-1-ol

Similarity: 0.96

Chemical Structure| 70448-03-2

[ 70448-03-2 ]

2-(Benzyloxy)propan-1-ol

Similarity: 0.96

Chemical Structure| 33106-64-8

[ 33106-64-8 ]

(S)-2-(Benzyloxy)propan-1-ol

Similarity: 0.96

Chemical Structure| 17325-85-8

[ 17325-85-8 ]

(S)-3-(Benzyloxy)propane-1,2-diol

Similarity: 0.93

Alcohols

Chemical Structure| 58530-76-0

[ 58530-76-0 ]

(R)-2,3-Bis(benzyloxy)propan-1-ol

Similarity: 0.96

Chemical Structure| 20196-71-8

[ 20196-71-8 ]

(S)-2,3-Bis(benzyloxy)propan-1-ol

Similarity: 0.96

Chemical Structure| 70448-03-2

[ 70448-03-2 ]

2-(Benzyloxy)propan-1-ol

Similarity: 0.96

Chemical Structure| 33106-64-8

[ 33106-64-8 ]

(S)-2-(Benzyloxy)propan-1-ol

Similarity: 0.96

Chemical Structure| 17325-85-8

[ 17325-85-8 ]

(S)-3-(Benzyloxy)propane-1,2-diol

Similarity: 0.93