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Chemical Structure| 190786-44-8
Chemical Structure| 190786-44-8
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Product Details of [ 190786-44-8 ]

CAS No. :190786-44-8 MDL No. :MFCD01938491
Formula : C27H31ClN2O6S Boiling Point : -
Linear Structure Formula :- InChI Key :UDGHXQPQKQPSBB-BOXHHOBZSA-N
M.W : 547.06 Pubchem ID :164521
Synonyms :
Bepotastine (besylate);TAU 284

Calculated chemistry of [ 190786-44-8 ]

Physicochemical Properties

Num. heavy atoms : 37
Num. arom. heavy atoms : 18
Fraction Csp3 : 0.33
Num. rotatable bonds : 9
Num. H-bond acceptors : 8.0
Num. H-bond donors : 2.0
Molar Refractivity : 145.82
TPSA : 125.41 Ų

Pharmacokinetics

GI absorption : Low
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -8.43 cm/s

Lipophilicity

Log Po/w (iLOGP) : 3.37
Log Po/w (XLOGP3) : 1.7
Log Po/w (WLOGP) : 5.48
Log Po/w (MLOGP) : 2.71
Log Po/w (SILICOS-IT) : 3.91
Consensus Log Po/w : 3.43

Druglikeness

Lipinski : 1.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.56

Water Solubility

Log S (ESOL) : -4.07
Solubility : 0.0467 mg/ml ; 0.0000854 mol/l
Class : Moderately soluble
Log S (Ali) : -3.95
Solubility : 0.0615 mg/ml ; 0.000112 mol/l
Class : Soluble
Log S (SILICOS-IT) : -5.96
Solubility : 0.0006 mg/ml ; 0.0000011 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 2.0
Synthetic accessibility : 4.14

Safety of [ 190786-44-8 ]

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

Application In Synthesis of [ 190786-44-8 ]

* 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 [ 190786-44-8 ]

[ 190786-44-8 ] Synthesis Path-Downstream   1~22

  • 1
  • [ 98-11-3 ]
  • [ 125602-71-3 ]
  • [ 125602-71-3 ]
YieldReaction ConditionsOperation in experiment
99.9% In ethanol at 50℃; Synthesis of (S)-4-{4-[(4-chlorophenyl) (2-pyridyl) methoxy] piperidine} butyric acid5 and preparation of crude bepotastine besilate 1 To a 30 L reactor was added ethanol (13 L), 4 (2.60 kg, 6.24 mol), sodium hydroxide(0.50 kg 12.48 mol) and water (2.6 L). The mixture was stirred at 25 C for 1h. Thenbenzene sulfonic acid (1.97 kg, 12.48 mol) in ethanol (2.6 L) was added and stirred for45 min. The mixture was concentrated at 50 C under reduced pressure until no furtherliquid could be removed. Acetonitrile (2.6 L) was added and the mixture was then concentratedat 55 C under reduced pressure until no further liquid could be removed.Acetonitrile (13 L) was added and the mixture was stirred for 2 hours. The mixture wasvacuum filtered and the filter cake was washed with acetonitrile (7.8 L). Benzene sulfonicacid (0.89 kg, 5.62 mol) was added to the mother liquor, which was heated to80 C and stirred for 0.5 h. The mixture was filtered and the filter cake was discarded.The mother liquor was cooled and crystallized, then centrifuged and washed with acetonitrile.The resulting solid was dried in vacuum at 45 C to obtain crude 1, 2.37 kg 69.5%, white powder with a purity of 99.9%. 1H-NMR DMSO-d6, 500 MHz, cf. reference10d 1.86 (m, 6H), 2.31 (t, 2H), 3.07 (br, 3H), 3.27 (br, 3H), 3.68 (br, 1H), 5.70(d, 1H), 7.32 (m, 4H), 7.40 (m, 4H), 7.64 (m, 3H), 7.82 (t, 1H, J7.6 Hz), 8.48 (d, 1H,J4.4 Hz), 12.00 (br, 2H); 13C-NMRDMSO-d6, 300MHzd 173.29, 161.42, 149.36,148.22, 140.91, 137.65, 132.61, 129.28 (2C), 129.20 (2C), 128.74 (2C), 128.26,125.95 (2C), 123.21, 120.98, 80.69, 70.68, 55.36, 49.01 (2C), 31.04, 28.25 (2C),19.61. MS (MH): Calcd for C21H25ClN2O3C6H6O3S, m/z 389.2. Found, m/z 388.16158.00.
93.49% In isopropyl alcohol at 0℃; for 3h; 1 Example 1: Preparation of bepotastine besilate A solution of benzenesulfonic acid monohydrate (35.51 g) was added to isopropanol (35 ml), stirred until complete dissolution and allowed to stand. Then, (+) - (S) -4- {4 - [(4-chlorophenyl) (2-pyridyl) methoxylpiperidyl} n-butyric acid (80.00 g) was dissolved in isopropanol , At a control temperature of 0 ° C and at a stirring speed of 120 rpm, a small amount of betahistine benzenesulfonate seed crystals was added, and the above-mentioned benzenesulfonic acid isopropanol solution was added dropwise. Dibi, continue to heat stirring 3 hours after the filter, filter cake with isopropyl alcohol watering. Wet goods 50 ~ 60 ° C vacuum drying, 102.30g of beastine besylate, yield: 93.49%. The purity of 99.51%, the largest single impurity 0.07%, ignition residue is not more than 0.2%
87% In acetonitrile at 10 - 15℃; for 12h; 8 Example 8: Preparation of Benettastin ((S) -benzenesulfonate (Formula (I)) 0.24 g of the intermediate prepared in Example 7 (Formula (VIII)) was dissolved in 3 mL of acetonitrile and the temperature was controlled at 10-15C, 85 mg of benzenesulfonic acid monohydrate and 5 mg of (S) bepotastine benzenesulfonate were added, stirred for 12 hours and filtered and dried to obtain 0.25 g of besostatin (S) -benzenesulfonate as a white solid , Yield 87%. The enantiomeric excess ee of product (S) -butastatin besylate was 100% by HPLC.
84.9% In acetonitrile at -5 - 0℃; for 12h; Reflux; 1.7; 2.7 (7) Preparation of compound 8 72.0g of compound 7 was dissolved in 700ml of acetonitrile, heated to reflux,Add 29.3g of benzenesulfonic acid,Cool down to -5°C0°C to crystallize for 12 hours, filter, and dry the solid at 45°C to constant weight.85.95 g of a white solid was obtained, with a yield of 84.9%, and its hydrogen spectrum and carbon spectrum are shown in Figures 11 and 12.
68% In ethyl acetate 1 According to the procedure disclosed in U.S. Patent No. 6,307,052, bepotastine (5.0 g, 12.9 mmol) was dissolved in 250 mi of ethyl acetate, and benzenesulfonic acid monohydrate (2.0 g, 11.4 mmol) was added thereto, followed by concentrating the resulting mixture under a reduced pressure. The residue was dissolved in 250 mi of ethyl acetate and the solution was kept for about 1 week in a refrigerator, to obtain a small quantity of crystals. The crystals were scraped with a specula, and the mixture was kept for another 2 days to induce further precipitation of crystals. The precipitated crystals were collected by filtration, and recrystallized from 50 rd of acetonitrile, to obtain 4.2 g of the title compound (yield: 68%) as an off-white crystalline powder.
68% In ethyl acetate 1 Comparative Example 1Preparation of Bepotastine Benzenesulfonic Acid SaltAccording to the procedure disclosed in U.S. Pat. No. 6,307,052, bepotastine (5.0 g, 12.9 mmol) was dissolved in 250 ml of ethyl acetate, and benzenesulfonic acid monohydrate (2.0 g, 11.4 mmol) was added thereto, followed by concentrating the resulting mixture under a reduced pressure. The residue was dissolved in 250 ml of ethyl acetate and the solution was kept for about 1 week in a refrigerator, to obtain a small quantity of crystals. The crystals were scraped with a specula, and the mixture was kept for another 2 days to induce further precipitation of crystals. The precipitated crystals were collected by filtration, and recrystallized from 50 ml of acetonitrile, to obtain 4.2 g of the title compound (yield: 68%) as an off-white crystalline powder.Then, bepotastine (45.0 g, 120 mmol) was dissolved in 450 ml of acetonitrile, and bezenesulfonic acid monohydrate (16.1 g, 100 mmol) was added thereto, followed by seeding the resulting mixture with the bepotastine benzenesulfonic acid salt obtained above. The mixture was stirred at room temperature for 12 hours, and the precipitate formed was filtered, to obtain 33 g of the title compound (yield: 66%). m.p.: 161-163° C. (reference value: 161.5° C.) water content: 0.4% (Karl-Fisher titrator) optical purity: 99.9% The result of X-ray powder diffraction analysis of the above crystalline powder showed peaks having a 100×I/Io value of at least 15% at 2 θ values listed in Table 2.
66% In acetonitrile 2 Then, bepotastine (45.0 g, 120 mmol) was dissolved in 450 mi of acetonitrile, and bezenesulfonic acid monohydrate (16. Ig, 100 mmol) was added thereto, followed by seeding the resulting mixture with the bepotastine benzenesulfonic acid salt obtained above. The mixture was stirred at room temperature for 12 hours, and the precipitate formed was filtered, to obtain 33g of the title compound (yield: 66%). m.p.: 161-163 °C (reference value: 161.5 "C) water content: 0.4% (Karl-Fisher titrator) optical purity: 99.9%
64% In acetonitrile at 20℃; for 12h; 8 4.0 g of bepotastine obtained in Example 7 was dissolved in 40 ml of acetonitrile, and 1.5 g of benzenesulfonic acid monohydrate was added thereto.To the resulting mixture, 0.05 g of bepotastine benzenesulfonate obtained in accordance with the method described in U.S. Patent No. 6,307,052 was added, followed by stirring at room temperature for 12 hours. The solid thus obtained was filtered to obtain 3.O g (yield: 64%, optical purity: 99.5%) of the title compound as a pale white crystalline powder.Melting point: 161-163 °C Water : 0.2% (Karl-Fischer water determination)1H-NMR(DMSO^6): δ 9.2(bs, IH), 8.5(d, IH), 7.8(t, IH), 7.6(m, 3H), 7.4(m, 4H), 7.3(m, 4H), 5.7(d, IH), 3.7(bs, 2H), 3.3(bs, 3H), 3.1 (bs, 2H), 2.3(t, 2H), 2.2(m, IH), 2.0(m, IH), 1.8(m, 3H), 1.7(m, IH).IR (KBr, cm-1): 3422, 2996, 2909, 2735, 2690, 2628, 1719, 1592, 1572, 1488, 1470, 1436, 1411, 1320, 1274, 1221, 1160, 1123, 1066, 1031, 1014, 996, 849, 830, 771, 759, 727, 693, 612, 564.1.
64% In acetonitrile at 20℃; for 12h; 8 Preparation of Bepotastine Benzenesulfonate Example 8 Preparation of Bepotastine Benzenesulfonate 4.0 g of bepotastine obtained in Example 7 was dissolved in 40 ml of acetonitrile, and 1.5 g of benzenesulfonic acid monohydrate was added thereto. To the resulting mixture, 0.05 g of bepotastine benzenesulfonate obtained in accordance with the method described in U.S. Pat. No. 6,307,052 was added, followed by stirring at room temperature for 12 hours. The solid thus obtained was filtered to obtain 3.0 g (yield: 64%, optical purity: 99.5%) of the title compound as a pale white crystalline powder.Melting point: 161163° C.Water: 0.2% (Karl-Fischer water determination)1H-NMR (DMSO-d6): δ 9.2 (bs, 1H), 8.5 (d, 1H), 7.8 (t, 1H), 7.6 (m, 3H), 7.4 (m, 4H), 7.3 (m, 4H), 5.7 (d, 1H), 3.7 (bs, 2H), 3.3 (bs, 3H), 3.1 (bs, 2H), 2.3 (t, 2H), 2.2 (m, 1H), 2.0 (m, 1H), 1.8 (m, 3H), 1.7 (m, 1H).IR (KBr, cm-1): 3422, 2996, 2909, 2735, 2690, 2628, 1719, 1592, 1572, 1488, 1470, 1436, 1411, 1320, 1274, 1221, 1160, 1123, 1066, 1031, 1014, 996, 849, 830, 771, 759, 727, 693, 612, 564.1.
In water; ethyl acetate 1.a According to the method described in U.S. Patent No. 6,307,052, 5.0 g of bepotastine was dissolved in 250 mi of ethyl acetate, 2.O g of benzenesulfonic acid monohydrate was added thereto, and the mixture was concentrated under a reduced pressure. After adding 250 ml of ethyl acetate thereto, the resulting mixture was allowed to be partially crystallized for about 1 week, and the resulting solid was harvested using spatula, and further allowed to be crystallized. The solid thus obtained was filtered and recrystallized using 50 mi of acetonitrile to obtain 4.2 g of the title compound as a cream-colored crystalline powder.
99.9 % ee In water; acetonitrile at 20℃; for 12h; 1.b 45 g of bepotastine was dissolved in 450 mi of acetonitrile, 16 g of benzenesulfonic acid monohydrate was added thereto, and bepotastine benzenesulfonate obtained in step a) was seeded thereto. The reaction mixture was stirred at room temperature for 12 hrs, followed by filtering the resulting solid to obtain 33 g of the title compound as a cream-colored crystalline. The obtained compound was employed for comparative tests.Melting point: 161 ~ 1630C (reference value : 161.5 °C ) Water content: 0.4% (Karl-Fischer titration) Optical purity: 99.9% The crystalline powder thus obtained was subjected to XRPD analysis, and the resulting XRPD spectrum of the crystalline powder showed major peaks having a relative peak intensity of at least 15% (1/I0: 1; the intensity of the peak, and I0; the intensity of the maximum peak), as shown in Table 1.
96 g In acetonitrile at 20℃; for 15h; 7 Preparation of Compound (IX), (+)-(S-4-[4-[(4-chloro phenyl)(2-pyridyl)methoxy]piperidino]butyric acid monobenzene sulfonate Example 7 Preparation of Compound (IX), (+)-(S-4-[4-[(4-chloro phenyl)(2-pyridyl)methoxy]piperidino]butyric acid monobenzene sulfonate The compound (VIII) (100 g), benzenesulfonic acid monohydrate (43 g) and acetonitrile (450 g) were added into a flask and stirred for 15 hours at room temperature in the presence of seeds. Then, the solution was filtered to get the compound (IX) (about 118 g). Through HPLC analysis, the optical purity can be determined as 99.77% [(S)-isomer:(R)-isomer=99.77:0.23]. Next, the compound (IX) (118 g) was dissolved in acetone (380 g) and water (24 g) in a flask under heating, followed by adding seeds at 50° C. and slow cooling to 0° C. for crystallization. After 2 hours of crystallization at 0° C., the compound (IX) (about 96 g) was isolated by filtration. Through HPLC analysis, the optical purity can be determined as 99.93% [(S)-isomer:(R)-isomer=99.93:0.07]. shows its X-ray diffraction pattern. Melting point of Compound (IX): 161-166° C. 1H NMR (DMSO-d6) of Compound (IX): δ 8.47 (m, 1H), 7.82 (m, 1H), 7.59 (m, 3H), 7.40 (m, 4H), 7.30 (m, 4H), 5.69 (s, 1H), 3.67 (br, 1H), 3.32 (br, 2H), 3.05 (br, 4H), 2.30 (t, 2H), 2.15 (br, 1H), 1.97 (br, 1H), 1.84 (m, 3H), 1.70 (br, 1H).
1.271 kg In acetonitrile Reflux; Large scale; 4.5 Step 5: Preparation of Bepotastine Besilate The yellow oil from Step (4) was added 17.5L acetonitrile. Then was added 0.504kg benzenesulfonic acid. Warmed to reflux. hot filtered, and the filtrate was cooled to 0 deg.C crystallization 10h, filtered to give benzenesulfonamide bepotastine 1.271 kg.
3 g In ethyl acetate for 12h; 21 Preparation of (S)-bipotastine benzenesulfonic acid salt (S)-bipotastine (5.0 g) is dissolved in 260 ml of ethyl acetate then 2 g of benzenesulfonic acid monohydrate was added to make a homogeneous solution. The solvent was removed from the solution under reduced pressure, and 260 ml of ethyl acetate was added to the residue, followed by stirring for 12 hours. The solvent was removed by recrystallization, 100 ml of acetonitrile was added to the residue, and the mixture was stirred at room temperature for 3 days to obtain the target compound (3 g).
502 g In ethyl acetate 1 Example 1 Preparation bepotastine besilate Will be 630g(S) -4- [4 - [(4-chlorophenyl) (2-pyridyl) methoxy]Piperidinyl] butyric acidDissolved in 4100 mL of ethyl acetate,Then 380 g of benzenesulfonic acid monohydrate were added to obtain a mixture.After concentrating the mixture under reduced pressure, 3200 mL of ethyl acetate was added to dissolve all the crystals, and the crystals were allowed to stand to obtain a crude product of bensebestin.The crude product was recrystallized from acetonitrile,Get 502gBetanibenzenesulfonateLight grayRounded edgesCrystal.

Reference: [1]Han; Xia; Sun; Zou [Organic Preparations and Procedures International, 2021, vol. 53, # 2, p. 206 - 210]
[2]Current Patent Assignee: HANGZHOU HEZE PHARMACEUTICAL TECH - CN106045974, 2016, A Location in patent: Paragraph 0021
[3]Current Patent Assignee: CHINA THREE GORGES UNIVERSITY; HUMANWELL HEALTHCARE (GROUP) CO., LTD. - CN106938995, 2017, A Location in patent: Paragraph 0056; 0057
[4]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES - CN113480521, 2021, A Location in patent: Paragraph 0020; 0050; 0064-0066; 0066; 0080-0081
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[6]Current Patent Assignee: HANMI SCIENCE CO LTD - US2010/137367, 2010, A1 Location in patent: Page/Page column 3
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[8]Current Patent Assignee: HANMI SCIENCE CO LTD - WO2008/153289, 2008, A2 Location in patent: Page/Page column 11
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  • 2
  • [ 1415692-17-9 ]
  • [ 98-11-3 ]
  • [ 125602-71-3 ]
  • [ 125602-71-3 ]
YieldReaction ConditionsOperation in experiment
64% In water; acetonitrile at 20℃; for 12h; Synthesis of (S)-Bepotastine Besilate (4) Bepotastine (50 g, 0.13 mol) was dissolved in 500 mL of acetonitrile, and benzenesulfonic acid monohydrate (20 g, 0.11 mol) was added to the reaction mixture. Bepotastine besilate (0.5 g,1.28 mmol) was seeded in the reaction mixture and stirred at rt for 12 h. The solid precipitate was filtered and dried. The product was obtained 38 g (yield: 64%, optical purity: 99.5% ee) as a pale white crystalline powder.
  • 4
  • [ 1560797-65-0 ]
  • [ 190786-44-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: acetic acid / water 2: sodium hydroxide / ethanol / 15 h / 20 °C 3: acetonitrile / 15 h / 20 °C
Multi-step reaction with 4 steps 1: [(2)H6]acetone; hexane / 15 h / 20 °C / Large scale 2: sodium hydroxide 3: sodium hydroxide / ethanol / 15 h / 20 °C 4: acetonitrile / 15 h / 20 °C
  • 5
  • [ 1560797-70-7 ]
  • [ 190786-44-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium hydroxide 2: sodium hydroxide / ethanol / 15 h / 20 °C 3: acetonitrile / 15 h / 20 °C
  • 6
  • [ 1560797-69-4 ]
  • [ 190786-44-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium hydroxide / ethanol / 15 h / 20 °C 2: acetonitrile / 15 h / 20 °C
  • 7
  • [ 4045-22-1 ]
  • [ 125602-71-3 ]
  • 8
  • [ CAS Unavailable ]
  • [ 190786-44-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: triethylamine / dichloromethane / 1 h / -70 °C / Large scale 1.2: 20 °C / Large scale 2.1: 5 h / 130 °C / Large scale 2.2: 15 h / 80 °C / Large scale 3.1: sodium iodide; potassium carbonate / acetonitrile / 15 h / 80 °C / Large scale 4.1: acetic acid / water 5.1: sodium hydroxide / ethanol / 15 h / 20 °C 6.1: acetonitrile / 15 h / 20 °C
Multi-step reaction with 7 steps 1.1: triethylamine / dichloromethane / 1 h / -70 °C / Large scale 1.2: 20 °C / Large scale 2.1: 5 h / 130 °C / Large scale 2.2: 15 h / 80 °C / Large scale 3.1: sodium iodide; potassium carbonate / acetonitrile / 15 h / 80 °C / Large scale 4.1: [(2)H6]acetone; hexane / 15 h / 20 °C / Large scale 5.1: sodium hydroxide 6.1: sodium hydroxide / ethanol / 15 h / 20 °C 7.1: acetonitrile / 15 h / 20 °C
Multi-step reaction with 4 steps 1: potassium carbonate / 24 h / Reflux 2: butanone / 4 h / Reflux 3: sodium hydroxide / ethanol / 12 h 4: ethyl acetate / 12 h
Multi-step reaction with 4 steps 1: potassium carbonate; potassium iodide / 24 h / Reflux 2: sodium / tetrahydrofuran / 4 h / Reflux 3: sodium hydroxide / 12 h / Reflux 4: ethyl acetate / 12 h
Multi-step reaction with 4 steps 1: potassium carbonate; potassium iodide / 24 h / Reflux 2: sodium / acetonitrile / 4 h / Reflux 3: sodium hydroxide / 12 h / Reflux 4: ethyl acetate / 12 h

  • 9
  • [ 26158-00-9 ]
  • [ 125602-71-3 ]
  • [ 125602-71-3 ]
YieldReaction ConditionsOperation in experiment
67.3% In ethyl acetate; (S) -4- [4-[(4-chlorophenyl) (2-pyridyl) methoxy] piperidino] butanoic acid 0.5 g (1.29mmol) Obtained according to Reference Example 5 was dissolved in ethyl acetate25 ml, and then benzene sulfonic acid monohydrate 0.20g (1.14mmol) was addedand concentrated under reduced pressure. ethyl acetate 25ml was again added tothe residue and allowed to stand for about 1 week, and the part of thecandy-like material is crystallized. Mixed with a spatula, further allowed tostand and the entire was crystallized. The crystals were recrystallized fromacetonitrile 5ml, and the desired product 0.42g (yield: 67.3%, optical purity:99.2% ee) was obtained as a pale gray prism crystal. [alpha] D20+ 6.0 (c = 5, MeOH). Melting point: 161 ~ 163 C
  • 10
  • [ CAS Unavailable ]
  • [ 190786-44-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: potassium carbonate / acetone / 7 h / Reflux 2: sodium hydroxide / ethanol; water / 20 °C 3: ethyl acetate
Multi-step reaction with 3 steps 1: potassium carbonate / acetone / 6 h / Reflux; Large scale 2: sodium hydroxide / ethanol / 2 h / Large scale 3: acetonitrile / Reflux; Large scale
Multi-step reaction with 3 steps 1: potassium carbonate / acetone / Reflux 2: sodium hydroxide / ethanol; water / 1 h / 25 °C 3: ethanol / 50 °C
Multi-step reaction with 3 steps 1: potassium carbonate / acetone / 10 h / Reflux 2: ethanol; sodium hydroxide / 8 h / 30 °C 3: acetonitrile / 12 h / -5 - 0 °C / Reflux

  • 11
  • [ 190730-39-3 ]
  • [ 190786-44-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium hydroxide / ethanol; water / 20 °C 2: ethyl acetate
Multi-step reaction with 2 steps 1: sodium hydroxide / ethanol / 12 h 2: ethyl acetate / 12 h
  • 12
  • [ CAS Unavailable ]
  • [ CAS Unavailable ]
  • [ 98-11-3 ]
  • [ 190786-44-8 ]
YieldReaction ConditionsOperation in experiment
75% Stage #1: (S)-(-)-2-((4-chlorophenyl)(piperidin-4-yloxy)methyl)pyridine; Ethyl 4-bromobutyrate With potassium carbonate In acetonitrile at 60℃; for 6h; Large scale; Stage #2: With sodium hydroxide In acetonitrile at 20℃; for 2h; Large scale; Stage #3: benzenesulfonic acid In acetonitrile at 70℃; Large scale; 1.3 Step (3): Preparation of bepotastine besilate The 1.514kg (S)-2-[(4-chlorophenyl)(4-piperidinyloxy)methyl]pyridine and 0.976kg ethyl 4-bromobutyrate was dissolved in 15L acetonitrile. Then add 0.692kg K2CO3 powder. Warmed to 60 deg.C. Continue stirring for 6 hours. Cooled to room temperature. Then add 1.5L 5N sodium hydroxide solution. Stirred for 2 hours. Add 0.252kg benzenesulfonic acid. Stir. Filter. To the filtrate was added 0.504kg benzenesulfonic acid. Warm to 70 deg.C. Hot filtration. The filtrate was cooled to 0 deg.C crystallization 10h, filtered to give benzenesulfonamide bepotastine 2.072kg, 75% yield.
  • 13
  • [ 210095-66-2 ]
  • [ 190786-44-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: hydrogenchloride / water / Large scale 2.1: potassium carbonate / acetonitrile / 6 h / 60 °C / Large scale 2.2: 2 h / 20 °C / Large scale 2.3: 70 °C / Large scale
Multi-step reaction with 4 steps 1: hydrogenchloride / water / Large scale 2: potassium carbonate / acetone / 6 h / Reflux; Large scale 3: sodium hydroxide / ethanol / 2 h / Large scale 4: acetonitrile / Reflux; Large scale
  • 14
  • [ 1313372-80-3 ]
  • [ 190786-44-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium hydroxide / 12 h / Reflux 2: ethyl acetate / 12 h
  • 15
  • [ 1016786-01-8 ]
  • [ 190786-44-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium / tetrahydrofuran / 4 h / Reflux 2: sodium hydroxide / 12 h / Reflux 3: ethyl acetate / 12 h
Multi-step reaction with 3 steps 1: sodium / acetonitrile / 4 h / Reflux 2: sodium hydroxide / 12 h / Reflux 3: ethyl acetate / 12 h
  • 16
  • [ 1555544-94-9 ]
  • [ 190786-44-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium / tetrahydrofuran / 4 h / Reflux 2: sodium hydroxide / 12 h / Reflux 3: ethyl acetate / 12 h
  • 17
  • [ 176022-47-2 ]
  • [ 125602-71-3 ]
  • 19
  • ethyl 4-(4-bromopiperidin-1-yl)butanoate [ No CAS ]
  • [ 176022-47-2 ]
  • [ 98-11-3 ]
  • [ 125602-71-3 ]
  • 20
  • [ CAS Unavailable ]
  • [ 190786-44-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: ammonium chloride; zinc / tetrahydrofuran; water / 1 h / 20 °C 2.1: sodium hydride / tetrahydrofuran / 8 h / 40 °C / Inert atmosphere 2.2: 16 h / 20 °C 2.3: 168 h
  • 21
  • [ 1563017-46-8 ]
  • [ 190786-44-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: C20H22ClIrN2O2S; sodium formate / water; isopropyl alcohol / 24 h / 30 °C / Inert atmosphere; Schlenk technique 2.1: ammonium chloride; zinc / tetrahydrofuran; water / 1 h / 20 °C 3.1: sodium hydride / tetrahydrofuran / 8 h / 40 °C / Inert atmosphere 3.2: 16 h / 20 °C 3.3: 168 h
  • 22
  • [ CAS Unavailable ]
  • [ 98-11-3 ]
  • [ 190730-42-8 ]
  • [ 190786-44-8 ]
YieldReaction ConditionsOperation in experiment
80 % ee Stage #1: 4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidine-1-yl]butyric acid ethyl ester With water; sodium hydroxide at 10 - 25℃; Stage #2: benzenesulfonic acid In dichloromethane; water 11 Process for preparation of Bepotastine besilate 1500 ml of Water, 250 gm of 2-[(S)-(4-Chlorophenyl)(piperidin-4- yloxy)methyl]pyridine L-tartrate and 300 gm of Potassium carbonate added into 3 lit RB Flask at Room temperature, stirred for 15 min, 127.5 gm of Ethyl 4- bromobutanoate added and heated to temperature 50-55°C and maintained for 13 hrs at same temperature and cooled to Room temperature. Toluene was added and distilled under vacuum. The resultant reaction mass was added into the Flask along with 1500 ml of Water at Room temperature. Solution of 80 gm of Sodium hydroxide in 500 ml of Water was added at 10-15°C, heated to 20-25°C and maintained for 3-4 hrs and 112.5 gm of Benzene sulfonic acid was added. 1500 ml of Dichloromethane was added and pH was adjusted to 3.7-3.9 with Sodium hydroxide solution. Dichloromethane extractions have given. Extracted Dichloromethane was treated with Carbon and distilled under vacuum. 500 ml of Acetone was added and stirred at 45°C for 30 min. The reaction mixture was then maintained at 0-5°C for 2-3 hrs, filtered the product and Dried. Yield: 200 gm; Purity: 99.52%; ee: 0.80
Same Skeleton Products
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Similar Product of
[ 190786-44-8 ]

Chemical Structure| 125602-71-3

A964833[ 125602-71-3 ]

(S)-4-(4-((4-Chlorophenyl)(pyridin-2-yl)methoxy)piperidin-1-yl)butanoic acid

Reason: Free-salt