* 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.
Reference：
[1] Journal of the American Chemical Society, 1951, vol. 73, p. 3635,3636
[2] Pharmaceutical Bulletin, 1953, vol. 1, p. 297,300
[3] Chemistry and Industry (London, United Kingdom), 1962, p. 1017
2
[ 111-42-2 ]
[ 122-96-3 ]
Yield
Reaction Conditions
Operation in experiment
79%
at 180 - 200℃; for 10 h; Autoclave; Inert atmosphere
Example 2Preparation of 1,4-bis(hydroxyethyl)piperazine from diethanolamine (no solvent)Example 2 was carried out under the conditions of example 1 in the same apparatus. 100 g of diethanolamine (II) and 10 g of catalyst A were used. Gas chromatographic analysis (GC column: 30 m RTX Amin) indicated, at quantitative diethanolamine conversion, that the reaction output comprised 79percent of 1,4-bis(hydroxyethyl)piperazine.
With hydrogenchloride In methanol; water for 2.5 h; Inert atmosphere
Under a nitrogen atmosphere, the reactor 100 ml, piperazine 8.6 g (0.1 mol) g of methanol 10.4 g, was added while stirring 35percent hydrochloric acid 10.4 g (0.1 mol), internal temperature It was referred to as 80 ° C. There, while maintaining the internal temperature below 80 ° C, 2- bromoethanol 8.7g of (0.07 mol) was added dropwise over 0.5 hours and then further continued for 2 hours and stirring remains the same temperature conditions. Since the reaction liquid was 4.2 where pH was measured, and added of 25percent NaOH aqueous solution 7.6 g, and the pH was adjusted to 8.5. Furthermore, maintaining the internal temperature at 80 ° C, stirring was continued for 2 hours to obtain a reaction solution 36.2g of colorless and transparent. Results The product was analyzed by gas chromatography, is 86.2percent for a yield of N-(2-hydroxyethyl) piperazine, the selectivity, N-(2-hydroxyethyl) piperazine, 91.9percent, N, N'- bis (2-hydroxyethyl) piperazine is 6.7percent, unknown content was 1.4percent. Along with other examples showing the results of Example 8 shown in Table 1.
Reference：
[1] European Journal of Organic Chemistry, 2012, # 34, p. 6752 - 6759
9
[ 75-21-8 ]
[ 110-85-0 ]
[ 103-76-4 ]
[ 122-96-3 ]
Reference：
[1] Journal of the American Chemical Society, 1954, vol. 76, p. 1126,1129
[2] Yakugaku Zasshi, 1955, vol. 75, p. 1367[3] Chem.Abstr., 1956, p. 10106
[4] Journal of Organic Chemistry, 1943, vol. 8, p. 342
[5] Patent: US2541260, 1949, ,
10
[ 75-21-8 ]
[ 110-85-0 ]
[ 122-96-3 ]
Reference：
[1] Journal of the American Chemical Society, 1935, vol. 57, p. 1988
[2] Helvetica Chimica Acta, 1959, vol. 42, p. 1156,1159
[3] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1984, vol. 38, # 9, p. 773 - 778
11
[ 64-17-5 ]
[ 111-42-2 ]
[ 122-96-3 ]
Reference：
[1] Beilstein Journal of Organic Chemistry, 2017, vol. 13, p. 329 - 337
12
[ 124-38-9 ]
[ 111-42-2 ]
[ 122-96-3 ]
[ 3356-88-5 ]
Reference：
[1] Beilstein Journal of Organic Chemistry, 2017, vol. 13, p. 329 - 337
13
[ 140-29-4 ]
[ 111-42-2 ]
[ 122-96-3 ]
Reference：
[1] Journal of the American Chemical Society, 1949, vol. 71, p. 359
14
[ 110-85-0 ]
[ 107-07-3 ]
[ 122-96-3 ]
Reference：
[1] Journal of the Chemical Society, 1908, vol. 93, p. 1802
[2] Patent: US2762744, 1951, ,
15
[ 141-43-5 ]
[ 122-96-3 ]
Reference：
[1] Yakugaku Zasshi, 1955, vol. 75, p. 1367[2] Chem.Abstr., 1956, p. 10106
16
[ 107-15-3 ]
[ 107-07-3 ]
[ 122-96-3 ]
Reference：
[1] Acta Poloniae Pharmaceutica, 1958, vol. 15, p. 351,352[2] Chem.Abstr., 1959, p. 8151
17
[ 2359-11-7 ]
[ 122-96-3 ]
[ 108-94-1 ]
Reference：
[1] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1982, vol. 18, # 11, p. 1215[2] Khimiya Geterotsiklicheskikh Soedinenii, 1982, vol. 18, # 11, p. 1560 - 1561
18
[ 100-47-0 ]
[ 111-42-2 ]
[ 122-96-3 ]
[ 7664-41-7 ]
[ 65-85-0 ]
Reference：
[1] Journal of the American Chemical Society, 1949, vol. 71, p. 359
19
[ 75-21-8 ]
[ 122-96-3 ]
Reference：
[1] Tohoku Daigaku Hisui Yoeki Kagaku Kenkyusho Hokoku, 1951, vol. 1, p. 87,90[2] Chem.Abstr., 1955, p. 3202
With hydrogen bromide; for 24h;Reflux; Inert atmosphere;
From a solution ofN,N?-bis(2-hydroxyethyl)piperazine (6.00 g, 34.4 mmol) in 48% HBr (50 mL) was distilled HBr (15 mL).The remaining mixture was stirred at reflux for 24 h, then allowed to cool to 25 C. Most of the solventwas removed in vacuo, and to the resulting residue was added acetone (40 mL). This mixture wasrefrigerated overnight, and the resulting precipitate was collected and dried in vacuo to afford the product(13.31 g, 84%) as a white solid: mp >240 C [Lit.20a mp 240-260 C (dec.)].
1,4-bis(2-hydroxyethyl)piperazine methyl carbonate[ No CAS ]
bis[1,4-(2-hydroxyethyl)-piperazine]carbonate[ No CAS ]
methyl bis(2-piperazinoethyl)carbonate[ No CAS ]
[ 616-38-6 ]
bis(methyl 2-piperazinoethyl)carbonate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With potassium carbonate; In bis(methyl 2-piperazinoethyl)carbonate;
EXAMPLE 2 Preparation of Bis(methyl 2-piperazinoethyl)carbonate A total of 180.0 grams (2.0 mole) of dimethyl carbonate, 17.4 grams (0.1 mole) of <strong>[122-96-3]1,4-bis(2-hydroxyethyl)piperazine</strong> and 1.0 gram (0.007 mole) of potassium carbonate were combined in a 250 milliliter round bottom flask equipped with a straight distillation head and a magnetic stirrer. The flask contents were heated to reflux under a nitrogen atmosphere. Initial reaction temperatures at reflux were 80 C. at the head and 88 C. on the kettle. A methanol/dimethyl carbonate azeotrope was removed overhead over a period of 7.5 hours. After this time, the flask contents were cooled and the kettle contents were analyzed by capillary gas chromatography (FlD) using a DB-1701 column. The <strong>[122-96-3]1,4-bis(2-hydroxyethyl)piperazine</strong> was totally converted to a mixture of methyl bis(2-piperazinoethyl)carbonate and bis(methyl 2-piperazinoethyl)carbonate. The kettle contents were heated for an additional period of 2.5 hours after which the reaction was stopped. The kettle contents were concentrated in vacuo at 20 mm Hg and a temperature of 60 C. using a rotary evaporator. A total of 26.6 grams of material which was about 88 percent pure in bis(methyl 2-piperazinoethyl)-carbonate was obtained. The major by-products were <strong>[122-96-3]1,4-bis(2-hydroxyethyl)piperazine</strong> methyl carbonate (ca. 1.5 percent) and bis[1,4-(2-hydroxyethyl)-piperazine]carbonate (ca. 9.9 percent).
EXAMPLE 4 N,N'-tetra-(2-hydroxyethyl)oxamide (2.64 g, 0.01 mol) and diethanolamine (2.10 g, 0.02 mol) are charged in a reaction flask equipped as described in Example 1 and the reaction mixture is heated to 210 C. for 20 hours. Acetone (15 ml) is then added and the precipitate is recovered by filtration and recrystallized from acetone. N,N'-bis-(2-hydroxyethyl)-piperazine (0.7 g) is thus obtained with a yield on N,N'-tetra(2-hydroxyethyl)oxamide of 40.2%, calculated on the starting diethanolamine.
Example 4 N,N--tetra-(2-hydroxyethyl)oxamide (2.64 g, 0.01 mol) and diethanolamine (2.10 g, 0.02 mol) are charged in a reaction flask equipped as described in Example 1 and the reaction mixture is heated to 210C for 20 hours. Acetone (15 ml) is then added and the precipitate is recovered by filtration and recrystallized from acetone. N,N--bis-(2-hydroxyethyl)-piperazine (0.7 g) is thus obtained with a yield on N,N--tetra(2-hydroxyethyl)oxamide of 40.2 %, calculated on the starting diethanolamine.
With 1H-imidazole; In N,N-dimethyl-formamide; at 20℃; for 3h;
Intermediate (68) : Preparation of2-{4-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-piperazin-l-yl}-ethanol; According to the similar procedure in the intermediate 64 by using piperazine (500mg, 5.80mmol) and 2-bromoethanol (0.90ml, 12.76mmol) of the target intermediate was obtained. This intermediate and imidazole (300mg, 4.40mmol) were dissolved in DMF (10ml). Therein, tert-butyldimethylsilyl chloride (TBDMS-Cl, 664mg, 4.40mmol) was added, and the reaction mixture was stirred at room temperature for 3 hours. Thereafter, the reaction mixture was poured into ethyl acetate, and washed with water. Combined organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (chloroform:methanol = 6:1) to give 675mg (yield for 2 steps: 63%, yellow oil) of the target compound.[1191] 1U NMR(400D, CDCI) delta 3.75(t, J=6.4Hz, 2H), 3.60(t, J=5.5Hz, 2H), 2.55~2.52(m,12H), 0.89(s, 9H), 0.059(s, 6H)
(2-chloro-quinazolin-4-yl)-(4-methoxy-phenyl)methylamine hydrochloride[ No CAS ]
[ 1217305-92-4 ]
Yield
Reaction Conditions
Operation in experiment
With sodium hydride; In tetrahydrofuran; N,N-dimethyl-formamide; at 65℃; for 2h;Inert atmosphere; sealed vial;
NaH (60% dispersion, 100 mg, 2.5 mmol) was placed in a 25 mL roundbottom flask under a blanket of inert gas and washed three times with hexanes. After decanting the last hexanes wash, the residue was dried with flowing N2 gas. A slurry of NaH was made in 3 mL THF. To this was added 2-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-ethanol (871 mg, 10 eq.) in 3 mL DMF, then (2-chloro-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine hydrochloride (150 mg, 0.5 mmol). The mixture was stirred at 65 C. in a sealed vial for 2 hours. The mixture was cooled, diluted with ethyl acetate (~10 mL) and washed with water. The organic layer was separated and passed through a 1 g silica cartridge, stripped, dissolved in DMSO (~1 mL), passed through a 0.45 mum filter, then purified by preparative RPLC, to yield the title compound. 1H NMR (CDCl3) delta 7.60 (d, 1H, J=8.2 Hz), 7.43-7.49 (m, 1H), 7.13 (d, 2H, J=9.0 Hz), 6.89-6.96 (m, 3H), 6.80-6.86 (m, 1H), 4.63 (t, 2H, J=6.5 Hz), 3.84 (s, 3H), 3.62 (t, 2H, J=5.5 Hz), 3.58 (s, 3H), 2.92 (t, 2H, J=6.4 Hz), 2.58-2.75 (m, 6H), 2.56 (t, 2H, J=5.4 Hz).
With disodium hydrogenphosphate; In water; at 120℃;Large scale;
The Examples and Comparative Example are run at 120C in a heated stainless steel 9 liter (L) stirred reactor. In Example 1 and 2 and Comparative Example A, 3 kilograms (kg) of a 33 percent by weight solution of piperazine in water is charged to the reactor. Ethylene oxide (EO) is metered into the reactor over several hours at 120C using a molar ratio of 1.9: 1.0 (EO:piperazine). In Example 1, 0.5 weight percent sulfuric acid (98% H2SO4) is added before the addition of the ethylene oxide. In Example 2, 5 weight percent monobasic sodium phosphate (NaH2P04) is added before the addition of the ethylene oxide. Subsequent to the completion of ethylene oxide addition, the reaction is allowed to agitate for several hours at reaction temperature to consume residual ethylene oxide. The resulting reaction mixtures are tested as produced. Foam is determined as follows: a 100 milliliter (ml) sample (e.g., the reacted mixture of Examples X to Y and Comparative Examples Z to W) is added to a 500 ml graduated cylinder containing a bubble diffuser connected to a dry air supply. The reaction mixture and diffuser, without air passing through it, are allowed to equilibrate for 2 minutes. The combined height (i.e., 100 ml plus the volume displaced by the diffuser) is measured and recorded in milliliters. After the 2 minute equilibration time, air is passed through the solution for one minute at a rate of 1000 ml/min then stopped. The resulting final foam volume is immediately measured in milliliters. The final volume minus the starting volume is reported as Foam Height (ml). The time for the foam to collapse until the first appearance of liquid is measured and reported as Break Time (seconds (s)). The results are listed in Table 1. The amount of glycol ether byproducts (combination of trimeric and tetrameric ethoxylated piperazine compounds) are analyzed by gas chromatography using an Agilent Technologies Model 7890 GC equipped with a J&W Scientific DB-WAX column. Identification of the compounds has been performed using Mass spectroscopy in positive chemical ionization mode and the amounts in weight percent are shown in Table 1. As used herein, trimeric piperazine compound is defined as the reaction product(s) of piperazine with three ethylene oxide and tetrameric piperazine compound is defined as the reaction product(s) of piperazine with four ethylene oxide. Color is determined according to ASTM 1544 using a Lovibond PFX195 tintometer with a path of 10.0mm.
[32] Catalyzed reaction of HEO: Under ambient conditions, catalyst (1.9 mmol; 5 mole %) and N-(2-hydroxyethyl) oxazolidinone (0.50 g, 38 mmol) were added to a 5 ml thick- walled Wheaton V-vial and capped using a red rubber septum screw cap. The vial was vented using a 18 gauge needle through the septum and the mixture was stuffed and heated at 180 C for 25 h. The conversion and selectivity was measured using ?H NMR analysis of the reaction mixture after 25 hours and is summarized in Table 1.
With dibutyltin dilaurate; In tetrahydrofuran; at 40℃; for 24h;
5 g (28.7 mmol) 1,4-piperazinediethanolwere dissolved in 25 mL tetrahydrofuran and 8.27 mL (57.4 mmol) 2-isocyanatoethyl methacrylate were dropwise added, the mixture being stirred at 40 oC for 24 hours in the presence of dibutyltin dilaurate. After complete reaction, the UDM-P iscollected by rotary evaporation under vacuum.
(6-(benzyloxy)-2-(4-(benzyloxy)phenyl)benzo[b]thiophen-3-yl)(4-fluorophenyl)methanone[ No CAS ]
(6-(benzyloxy)-2-(4-(benzyloxy)phenyl)benzo[b]thiophen-3-yl)(4-(2-(4-(2-hydroxyethyl)piperazin-1-yl)ethoxy)phenyl)methanone[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
46%
With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 50℃;Inert atmosphere;
(6- (Benzyloxy) -2 - (4- (benzyloxy)phenyl)benzo [b] thiophen- 3-yl) (4- (2 - (4- (2 - hydroxyethyl)piperazin-l-yl)ethoxy)phenyl)methanone Under an atmosphere of nitrogen, a solution of (6-(benzyloxy)-2-(4- (benzyloxy)phenyl)benzo[b]thiophen-3-yl)(4-fluorophenyl)methanone (300 mg, 0.55 mmol) in DMF (1 mL) was treated with 2,2'-(piperazine-l,4-diyl)diethanol (384 mg, 2.2 mmol) and then with sodium hydride (60% in mineral oil) (44 mg, 1.1 mmol) and the mixture was heated at 50C overnight. The cooled mixture was treated with 4M HC1 in 1,4-dioxane (0.1 mL) and then the product was subjected directly to purification by mass-directed automated preparative HPLC (formic acid modifier) to afford the title compound (177 mg, 0.25 mmol, 46% yield). LCMS RT = 1.21 min, ES+ve m/z 699 [M+H]+.
(E)-but-2-enedioic acid-2-{4-[2-((E)-3-methoxycarbonyl-acryloyloxy)-ethyl]-piperazin-1-yl}-ethyl ester methyl ester dihydrochloride[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
42%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 0 - 23℃; for 14h;
To a stirred suspension of monomethyl fumarate (1.64 g; 12.6 mmol) in drydichloromethane (30 mL) were added successively N-ethyl-N?-(3-methylaminopropyl)carbodiimide hydrochloride (2.4 g; 12.6 mmol), 1,4-bis(2- hydroxyethyl) piperazine (1 g; 5.7 mmol) and DMAP (70 mg; 0.6 mmol) at 0C. Thesuspension was allowed to warm to room temperature (23C) and stirring was continued overnight (for 14 hours). The mixture was diluted with additional dichloromethane (50 mL), washed with water (2 x 70 mL) and dried with sodium sulphate. After the removal of the solvent the resulting crude product was purified via silicagel chromatography (eluent: ethylacetate/triethylamine 99:1). The resulting substance was dissolved indichloromethane and HC1 (3M in BuOH; 4 eq.) was added. The precipitated product was collected via filtration.Yield: 1.14 g (2.4 mmol; 42%)
(E)-but-2-enedioic acid-2-{4-[2-((E)-3-methoxycarbonyl-acryloyloxy)-ethyl]-piperazin-1-yl}-ethyl ester methyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
42%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 0 - 23℃; for 14h;
Example 1: (E)-But-2-enedioic acid -2-{4-[2-((E)-3-methoxycarbonyl-acryloyloxy)- ethyl] -piperazin- 1-yl}-ethyl ester methyl ester To a stirred suspension of monomethyl fumarate (1.64 g; 12.6 mmol) in drydichloromethane (30 mL) were added successively N-ethyl-N?-(3-methylaminopropyl)carbodiimide hydrochloride (2.4 g; 12.6 mmol), 1,4-bis(2- hydroxyethyl) piperazine (1 g; 5.7 mmol) and DMAP (70 mg; 0.6 mmol) at 0C. The suspension was allowed to warm to room temperature (23C) and stirring was continued overnight (for 14 hours). The mixture was diluted with additional dichloromethane (50 mL), washed with water (2 x 70 mL) and dried over sodium sulfate. After the removal of the solvent the resulting crude product was purified via silicagel chromatography(eluent: ethyl acetate/triethylamine 99:1).Yield: 970 mg (2.4 mmol; 42%)
[Pd(1,4-bis(2-hydroxyethyl)piperazine)Cl2][ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In water; at 50℃; for 0.5h;pH 2 - 3;
Pd(BHEP)Cl2 was prepared by dissolving K2PdCl4 (0.92 g, 2.82 mmol) in 10 mL waterwith stirring. The clear solution of [PdCl4]2- was filtered and <strong>[122-96-3]1,4-bis(2-hydroxyethyl)piperazine</strong> (0.491 g, 2.82 mmol) dissolved in 10 mL H2O was added dropwise to the stirredsolution. The pH was adjusted to 2-3 by addition of HCl and/or NaOH. A yellowish-brownprecipitate of Pd(BHEP)Cl2 was formed and stirred for a further 30 min at 50 C. After filteringoff the precipitate, it was thoroughly washed with H2O, ethanol, and diethyl ether.An orange crystalline precipitate was obtained after recrystallization from 2 : 1 methanol/water mixture. (Found: C, 27.3; H, 5.3; N, 7.8%. Calcd for C8H18N2O2PdCl2(F.Wt = 351.55): C, 27.33; H, 5.17; N, 7.97%). IR: nuO-H (st) at 3429 cm-1, nuC-H (st) at3018, 2983, 2949, and 2891 cm-1, nuPd-N at 472 cm-1, nuPd-Cl at 333 and 324 cm-1.
[Pd(1,4-bis(2-hydroxyethyl)piperazine)Cl2][ No CAS ]
Yield
Reaction Conditions
Operation in experiment
92%
In water; at 70℃;
[Pd(BHEP)Cl2] was prepared by heating PdCl2 (0.177 g, 1.0 mmol) and KCl (0.149 g, 2.0 mmol) in minimumwater to 70 C under stirring. The clear solution of [PdCl4]2- was cooled to 25 C, filtered and<strong>[122-96-3]1,4-bis(2-hydroxyethyl)piperazine</strong> (0.174 g, 1.0 mmol) was added to the stirred solution. The pH of thesolution was adjusted to 2-3 by the addition of HCl. The solution was evaporated to a small volume(20 mL) under vacuum, after which an orange crystalline precipitate of [Pd(BHEP)Cl2] was formed oncooling. The precipitate was filtered off and washed with water; yield 92%. Anal. Calcd for C8H18N2O2PdCl2(%) (MW = 351.55): C, 27.33; H, 5.17; N, 7.97. Found: C, 27.3; H, 5.3; N, 7.8%. Crystals suitable for X-raycrystallography were obtained by the recrystallization of [Pd(BHEP)Cl2] from hot acetonitrile/water,followed by slow evaporation during which orange crystals were obtained
With hydrogenchloride; In methanol; water; for 2.5h;pH 8.5;Inert atmosphere;
Under a nitrogen atmosphere, the reactor 100 ml, piperazine 8.6 g (0.1 mol) g of methanol 10.4 g, was added while stirring 35% hydrochloric acid 10.4 g (0.1 mol), internal temperature It was referred to as 80 C. There, while maintaining the internal temperature below 80 C, 2- bromoethanol 8.7g of (0.07 mol) was added dropwise over 0.5 hours and then further continued for 2 hours and stirring remains the same temperature conditions. Since the reaction liquid was 4.2 where pH was measured, and added of 25% NaOH aqueous solution 7.6 g, and the pH was adjusted to 8.5. Furthermore, maintaining the internal temperature at 80 C, stirring was continued for 2 hours to obtain a reaction solution 36.2g of colorless and transparent. Results The product was analyzed by gas chromatography, is 86.2% for a yield of N-(2-hydroxyethyl) piperazine, the selectivity, N-(2-hydroxyethyl) piperazine, 91.9%, N, N'- bis (2-hydroxyethyl) piperazine is 6.7%, unknown content was 1.4%. Along with other examples showing the results of Example 8 shown in Table 1.
With hydrogen; In water; at 180℃; under 15001.5 Torr;
In a tubular reactor in a fixed bed, The temperature of the fixed bed reaction zone is 180 C, Hydrogen pressure 2. OMpa, in Co / gamma -Al23 (the main ingredient Co content of 35%, 50g) as a catalyst, Dihydroxyethylpiperazine was introduced into the tubular reactor at a flow rate of 1.5 ml / min 40% aqueous solution, and the resulting reaction solution had a piperazine content of 15.7%
In a tubular reactor in a fixed bed, The fixed bed reaction zone has a temperature of 200 C and a hydrogen pressure 4. OMpa, in the Cu / gamma -Al23 (the main component of the Cu content percentage of 40%, 50g) as a catalyst to 1. Oml / min To a tubular reactor was bubbled through a 40% methanol solution of hydroxyethylpiperazine, In the resulting reaction solution, piperazine is combined The content of the product was 81.4% (the content of piperazine was 68.7% and the content of N-methylpiperazine was 12.7%). Using the distillation method, Can be one of the high value of N-methyl piperazine separation, to further improve the value of the product
Buttersaeure-N,N'-bis-<ethanol>-piperazindiester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
87%
General procedure: Carboxylic acid (1.5 eq per hydroxyl group) was placed into a round bottom flask along with a stir bar and carbonyl diimidazole (CDI, 1.6 eq per hydroxyl group). Dichloromethane (DCM, 10 mL per gram carboxylic acid) was added carefully while stirring (500 rpm) at ambient temperature. Immediate formation of carbon dioxide indicated conversion of corresponding acid to the acyl donor (caution: too quick CO2 formation may result in strong foaming. Do not seal the flask). After a couple of minutes, a clear solution was obtained and stirring was continued for 15 minutes. N-Hydroxyalkyl compound (5 mmol) was added at ambient temperature and the reaction mixture was stirred overnight. When ESI-MS indicated full conversion of starting materials the reaction was quenched by addition of methanol, converting excess acyl donor to methyl ester. The system was diluted by addition of further DCM and was subject to extraction with saturated sodium bicarbonate solution (3x). Separation of organic phase, drying over sodium sulfate and evaporation of any volatiles in vacuo yielded the product as colorless oil.
General procedure: Carboxylic acid (1.5 eq per hydroxyl group) was placed into a round bottom flask along with a stir bar and carbonyl diimidazole (CDI, 1.6 eq per hydroxyl group). Dichloromethane (DCM, 10 mL per gram carboxylic acid) was added carefully while stirring (500 rpm) at ambient temperature. Immediate formation of carbon dioxide indicated conversion of corresponding acid to the acyl donor (caution: too quick CO2 formation may result in strong foaming. Do not seal the flask). After a couple of minutes, a clear solution was obtained and stirring was continued for 15 minutes. N-Hydroxyalkyl compound (5 mmol) was added at ambient temperature and the reaction mixture was stirred overnight. When ESI-MS indicated full conversion of starting materials the reaction was quenched by addition of methanol, converting excess acyl donor to methyl ester. The system was diluted by addition of further DCM and was subject to extraction with saturated sodium bicarbonate solution (3x). Separation of organic phase, drying over sodium sulfate and evaporation of any volatiles in vacuo yielded the product as colorless oil.
General procedure: N-Hydroxyalkyl compound (5 mmol) was suspended in excess carboxyl acid anhydride (> 100 mmol, > 20 eq.) in a round bottom flask while stirring (magnetic stir bar, 500 rpm). The mixture was cooled in an ice bath and sulfuric acid (> 96%, 3 drops) was carefully added as catalyst. Stirring was continued until a clear solution was obtained. When ESI-MS indicated full conversion of starting materials the reaction mixture was poured on ice. The system was stirred for 2 or more hours in order to hydrolyze any anhydride. The mixture was neutralized by addition of sodium bicarbonate and extracted with dichloromethane (3x). Separation of organic phase, drying over sodium sulfate and evaporation of any volatiles in vacuo yielded the product as colorless oil.
General procedure: N-Hydroxyalkyl compound (5 mmol) was suspended in excess carboxyl acid anhydride (> 100 mmol, > 20 eq.) in a round bottom flask while stirring (magnetic stir bar, 500 rpm). The mixture was cooled in an ice bath and sulfuric acid (> 96%, 3 drops) was carefully added as catalyst. Stirring was continued until a clear solution was obtained. When ESI-MS indicated full conversion of starting materials the reaction mixture was poured on ice. The system was stirred for 2 or more hours in order to hydrolyze any anhydride. The mixture was neutralized by addition of sodium bicarbonate and extracted with dichloromethane (3x). Separation of organic phase, drying over sodium sulfate and evaporation of any volatiles in vacuo yielded the product as colorless oil.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
