242478-37-1

Basic information

• Product Name: Solifenacin
• Synonyms: Unii-A8910sqj1u;3,4-dihydro-1-phenyl-(1S)-2(1H)-Isoquinolinecarboxylic acid (3R)-1-azabicyclo[2.2.2]oct-3-yl ester;YM 905;(1S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate;2(1H)-Isoquinolinecarboxylicacid, 3,4-dihydro-1-phenyl-, (3R)-1-azabicyclo[2.2.2]oct-3-yl ester, (1S)-;Solif·Nacin;4R-Hydroxy Solifenacin;4R-Hydroxy Solifenacin N-Oxide
• CAS NO: 242478-37-1
• Molecular Formula: C₂₃H₂₆N₂O₂
• Molecular Weight: 362.47
• Product Categories: VESICARE
• Mol File: 242478-37-1.mol
• Article Data: 40

Chemical Properties

• Boiling Point: 505.5 °C at 760 mmHg
• Flash Point: 259.5 °C
• Appearance: /
• Density: 1.24 g/cm³
• Vapor Pressure: 2.41E-10mmHg at 25°C
• Refractive Index: 1.648
• PKA: 9.03±0.33(Predicted)
• CAS DataBase Reference: Solifenacin(CAS DataBase Reference)
• NIST Chemistry Reference: Solifenacin(242478-37-1)
• EPA Substance Registry System: Solifenacin(242478-37-1)

Safety Data

• Hazardous Substances Data: 242478-37-1(Hazardous Substances Data)

Usage

Uses

muscarinic M3 antagonist

InChI:InChI=1/C23H26N2O2/c26-23(27-21-16-24-13-10-18(21)11-14-24)25-15-12-17-6-4-5-9-20(17)22(25)19-7-2-1-3-8-19/h1-9,18,21-22H,10-16H2/t21-,22-/m0/s1

Synthetic route

C34H29NO2P(1+)*Cl(1-) + (R)-quinuclidin-3-ol (25333-42-0) → solifenacin (242478-37-1)

Conditions	Yield
In toluene at 60 - 70℃; Temperature;	96.8%

(S)-N-carboxylic acid ethyl ester-1-phenyl-1,2,3,4-tetrahydroisoquinoline (180468-42-2) + (R)-quinuclidin-3-ol (25333-42-0) → solifenacin (242478-37-1)

Conditions	Yield
With sodium hydride; 1-butyl-3-methylimidazolium Tetrafluoroborate In N,N-dimethyl-formamide at 100℃; for 6h; Temperature; Concentration;	95.1%
With sodium hydride In toluene for 3h; Heating;	89%
Stage #1: (R)-quinuclidin-3-ol With sodium hydride In toluene; mineral oil at 0℃; for 0.25h; Inert atmosphere; Stage #2: (S)-N-carboxylic acid ethyl ester-1-phenyl-1,2,3,4-tetrahydroisoquinoline In toluene; mineral oil at 130℃; for 8h; Inert atmosphere; Dean-Stark;	88%

(3S)-1-azabicyclo[2.2.2]octan-3-yl 1H-imidazole-1-carboxylate + (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline (22990-19-8, 96719-89-0, 118864-75-8) → solifenacin (242478-37-1)

Conditions	Yield
In tetrahydrofuran at 0℃; for 2h; Inert atmosphere;	92.2%

(3R)-1-azabicyclo[2,2,2]oct-3-yl pentafluorophenylcarbonate (1459721-13-1) + (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline (22990-19-8, 96719-89-0, 118864-75-8) → solifenacin (242478-37-1)

Conditions	Yield
In toluene at 10 - 15℃; Temperature; Time; Solvent;	91%
In toluene at 10 - 15℃; Solvent; Temperature;	91%

Solifenacin hydrochloride → solifenacin (242478-37-1)

Conditions	Yield
With ammonium hydroxide In water pH=9 - 10;	90%

4-nitrophenyl (1S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate (1229227-22-8) + (R)-quinuclidin-3-ol (25333-42-0) → solifenacin (242478-37-1)

Conditions	Yield
Stage #1: (R)-quinuclidin-3-ol With 18-crown-6 ether; sodium hydride In toluene; mineral oil Inert atmosphere; Stage #2: 4-nitrophenyl (1S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate In toluene; mineral oil at 20 - 110℃; for 18h; Inert atmosphere;	74%
Stage #1: (R)-quinuclidin-3-ol With sodium hydride In N,N-dimethyl-formamide; mineral oil Inert atmosphere; Stage #2: 4-nitrophenyl (1S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate In N,N-dimethyl-formamide; mineral oil at 110℃; for 4h; Inert atmosphere;	70%

(S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline (22990-19-8, 96719-89-0, 118864-75-8) + (R)-quinuclidin-3-ol (25333-42-0) → solifenacin (242478-37-1)

Conditions	Yield
Stage #1: (R)-quinuclidin-3-ol With sodium methylate In toluene at 5℃; Inert atmosphere; Reflux; Stage #2: (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline In N,N-dimethyl-formamide; toluene at 60℃; Reflux;	72%
Stage #1: (R)-quinuclidin-3-ol With 1,1'-Carbonyl-di-(1,2,4-triazole); triethylamine In Isopropyl acetate at 20℃; for 2h; Stage #2: (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline In Isopropyl acetate for 4h; Product distribution / selectivity; Heating / reflux;

propyl (1S)-1-phenyl-3,4-dihydro-2(1H)isoquinolinecarboxylate + (R)-quinuclidin-3-ol (25333-42-0) → solifenacin (242478-37-1)

Conditions	Yield
Stage #1: (R)-quinuclidin-3-ol With sodium hydride In toluene at 80℃; for 1h; Stage #2: propyl (1S)-1-phenyl-3,4-dihydro-2(1H)isoquinolinecarboxylate In toluene for 18h; Reflux;	63.9%

(3R)-1-azabicyclo[2.2.2]octan-3-ol hydrochloride + (S)-N-carboxylic acid ethyl ester-1-phenyl-1,2,3,4-tetrahydroisoquinoline (180468-42-2) → solifenacin (242478-37-1)

Conditions	Yield
Stage #1: (3R)-1-azabicyclo[2.2.2]octan-3-ol hydrochloride With sodium methylate at 5 - 30℃; Inert atmosphere; Stage #2: (S)-N-carboxylic acid ethyl ester-1-phenyl-1,2,3,4-tetrahydroisoquinoline In N,N-dimethyl-formamide; toluene at 60℃; Reflux;	51%

(S)-N-carboxylic acid ethyl ester-1-phenyl-1,2,3,4-tetrahydroisoquinoline (180468-42-2) + sodium (R)-quinuclidin-3-ol → solifenacin (242478-37-1)

Conditions	Yield
Stage #1: sodium (R)-quinuclidin-3-ol With sodium methylate In N,N-dimethyl-formamide; toluene at 25℃; Inert atmosphere; Reflux; Stage #2: (S)-N-carboxylic acid ethyl ester-1-phenyl-1,2,3,4-tetrahydroisoquinoline In N,N-dimethyl-formamide; toluene at 70℃; Reflux;	50%

(S)-N-carboxylic acid ethyl ester-1-phenyl-1,2,3,4-tetrahydroisoquinoline (180468-42-2) + (R)-quinuclidin-3-ol (25333-42-0) → (1S)-3,4-dihydro-1-phenyl-2-(1H)-isoquinolinecarboxylic acid (3S)-1-azabicyclo[2.2.2]oct-3-yl ester (732228-02-3) + (3R)-1-azabicyclo[2.2.2]oct-3-yl (1R)-3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylate (740780-79-4) + (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline (22990-19-8, 96719-89-0, 118864-75-8) + solifenacin (242478-37-1)

Conditions	Yield
With potassium 2-methylbutan-2-olate In toluene at 90℃; for 3h; Product distribution / selectivity;	A 1.1% B 3.2% C 6% D n/a

(S)-N-carboxylic acid ethyl ester-1-phenyl-1,2,3,4-tetrahydroisoquinoline (180468-42-2) → (1S)-3,4-dihydro-1-phenyl-2-(1H)-isoquinolinecarboxylic acid (3S)-1-azabicyclo[2.2.2]oct-3-yl ester (732228-02-3) + (3R)-1-azabicyclo[2.2.2]oct-3-yl (1R)-3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylate (740780-79-4) + solifenacin (242478-37-1)

Conditions	Yield
Stage #1: (R)-quinuclidin-3-ol With sodium hydride In toluene for 0.166667h; Stage #2: (S)-N-carboxylic acid ethyl ester-1-phenyl-1,2,3,4-tetrahydroisoquinoline In toluene at 26 - 110℃; for 4.33333h; Product distribution / selectivity;

1-phenyl-3,4-dihydroisoquinoline (52250-50-7) → solifenacin (242478-37-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: NaBH4 / ethanol / 60 h / 20 °C 2: 100 percent / K2CO3 / CH2Cl2 / 20 °C 3: 89 percent / NaH / toluene / 3 h / Heating View Scheme
Multi-step reaction with 4 steps 1.1: methanol; sodium tetrahydroborate / water / 5.42 h / 20 - 34 °C 2.1: D-tartaric acid / methanol; ethyl acetate / 2.08 h / 28 - 64 °C / Resolution of racemate 2.2: 1.17 h / pH 8 - 9 3.1: sodium carbonate / toluene / 2.17 h / 0 - 28 °C 4.1: toluene / 5 h / 55 - 115 °C 4.2: 10 h / 55 - 115 °C View Scheme

N-phenethylbenzamide (3278-14-6) → solifenacin (242478-37-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: P2O5; POCl3 / xylene / 2.5 h / Heating 2: NaBH4 / ethanol / 60 h / 20 °C 3: 100 percent / K2CO3 / CH2Cl2 / 20 °C 4: 89 percent / NaH / toluene / 3 h / Heating View Scheme
Multi-step reaction with 5 steps 1.1: PPA / water / 4.25 h / 14.9 - 165 °C 1.2: 0.17 h / 28 - 42 °C / pH 2.1 - 7.12 2.1: methanol; sodium tetrahydroborate / water / 5.42 h / 20 - 34 °C 3.1: D-tartaric acid / methanol; ethyl acetate / 2.08 h / 28 - 64 °C / Resolution of racemate 3.2: 1.17 h / pH 8 - 9 4.1: sodium carbonate / toluene / 2.17 h / 0 - 28 °C 5.1: toluene / 5 h / 55 - 115 °C 5.2: 10 h / 55 - 115 °C View Scheme

(S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline (22990-19-8, 96719-89-0, 118864-75-8) → solifenacin (242478-37-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 100 percent / K2CO3 / CH2Cl2 / 20 °C 2: 89 percent / NaH / toluene / 3 h / Heating View Scheme
Multi-step reaction with 2 steps 1.1: pyridine / toluene / 20 - 80 °C 2.1: sodium hydride / tetrahydrofuran / 0.75 h / Reflux 2.2: 1.5 h / Reflux View Scheme
Multi-step reaction with 2 steps 1.1: bis-(p-nitrophenyl) carbonate / N,N-dimethyl-formamide / 25 - 30 °C 1.2: 3 h / 25 - 30 °C 1.3: 25 - 30 °C / pH 1 - 2 2.1: ammonium hydroxide / water / pH 9 - 10 View Scheme

(S)-N-carboxylic acid ethyl ester-1-phenyl-1,2,3,4-tetrahydroisoquinoline (180468-42-2) + (R)-quinuclidin-3-ol (25333-42-0) → (1S)-3,4-dihydro-1-phenyl-2-(1H)-isoquinolinecarboxylic acid (3S)-1-azabicyclo[2.2.2]oct-3-yl ester (732228-02-3) + (3S)-1-azabicyclo[2.2.2]oct-3-yl (1R)-3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylate (774517-20-3) + (3R)-1-azabicyclo[2.2.2]oct-3-yl (1R)-3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylate (740780-79-4) + solifenacin (242478-37-1)

Conditions	Yield
With sodium ethanolate In water; N,N-dimethyl-formamide; toluene at 20℃; for 8h; Product distribution / selectivity; Heating;

methyl (1S)-1-phenyl-3,4-dihydro-2(1H)-isoquinoline-carboxylate + sodium methylate (124-41-4) + (R)-quinuclidin-3-ol (25333-42-0) → (1S,3'R)-2'-methylquinuclidin-3'-yl-1-phenyl-1,2,3,4-tetrahydrolsoquinoline-2-carboxylate + solifenacin (242478-37-1)

Conditions	Yield
In N,N-dimethyl-formamide; toluene for 8h;

benzyl (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate + sodium phenyl-methanolate (20194-18-7) + (R)-quinuclidin-3-ol (25333-42-0) → (1S,3'R)-2'-benzylquinuclidin-3'-yl-1-phenyl-1,2,3,4-terahydroisoquinoline-2-carboxylate + solifenacin (242478-37-1)

Conditions	Yield
In N,N-dimethyl-formamide; toluene for 8h;

C18H18ClNO2 + (R)-quinuclidin-3-ol (25333-42-0) → solifenacin (242478-37-1)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; toluene at 80 - 100℃; for 18h; Product distribution / selectivity;

(S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline (22990-19-8, 96719-89-0, 118864-75-8) + 1,1'-carbonyldiimidazole (530-62-1) + (R)-quinuclidin-3-ol (25333-42-0) → solifenacin (242478-37-1)

Conditions	Yield
Stage #1: (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline; 1,1'-carbonyldiimidazole In toluene at 20℃; for 2.75h; Stage #2: (R)-quinuclidin-3-ol With sodium hydride In N,N-dimethyl-formamide; toluene at 20 - 85℃;

(S)-N-carboxylic acid ethyl ester-1-phenyl-1,2,3,4-tetrahydroisoquinoline (180468-42-2) + (R)-quinuclidin-3-ol (25333-42-0) → (1S)-3,4-dihydro-1-phenyl-2-(1H)-isoquinolinecarboxylic acid (3S)-1-azabicyclo[2.2.2]oct-3-yl ester (732228-02-3) + (3R)-1-azabicyclo[2.2.2]oct-3-yl (1R)-3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylate (740780-79-4) + solifenacin (242478-37-1)

Conditions	Yield
With potassium tert-butylate In toluene at 90℃; for 3 - 10h; Product distribution / selectivity;

phenyl (S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate + (R)-quinuclidin-3-ol (25333-42-0) → solifenacin (242478-37-1)

Conditions	Yield
With sodium hydride In N,N-dimethyl acetamide at 0 - 60℃;
Stage #1: (R)-quinuclidin-3-ol With sodium hydride In ISOPROPYLAMIDE; mineral oil at 0 - 20℃; Stage #2: phenyl (S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate In ISOPROPYLAMIDE; toluene; mineral oil at 20 - 60℃;

(+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydro-isoquinoline-2-carboxylate di-p-toluoyl-L-tartrate → solifenacin (242478-37-1)

Conditions	Yield
With sodium hydrogencarbonate In water at 0 - 15℃; Product distribution / selectivity;

(+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydro-isoquinoline-2-carboxylate oxalate → solifenacin (242478-37-1)

Conditions	Yield
With sodium hydrogencarbonate In water; ethyl acetate at 0 - 30℃;

(+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydro-isoquinoline-2-carboxylate hydrochloride → solifenacin (242478-37-1)

Conditions	Yield
With sodium hydrogencarbonate In water; ethyl acetate at 0 - 30℃;

(S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carbonyl chloride (1195949-26-8) + (R)-quinuclidin-3-ol (25333-42-0) → solifenacin (242478-37-1)

Conditions	Yield
Stage #1: (R)-quinuclidin-3-ol With sodium hydride In tetrahydrofuran for 0.75h; Reflux; Stage #2: (S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carbonyl chloride In tetrahydrofuran for 1.5h; Reflux;
Stage #1: (R)-quinuclidin-3-ol With sodium hydride In tetrahydrofuran for 0.75h; Reflux; Stage #2: (S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carbonyl chloride In tetrahydrofuran for 1.5h; Reflux;

2-(1H-imidazole-2-ylcarbonyl)-(1S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline (1029430-94-1) + (R)-quinuclidin-3-ol (25333-42-0) → solifenacin (242478-37-1)

Conditions	Yield
Stage #1: 2-(1H-imidazole-2-ylcarbonyl)-(1S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline With titanium(IV) isopropylate In tetrahydrofuran at 20℃; for 0.5h; Stage #2: (R)-quinuclidin-3-ol With sodium hydride In tetrahydrofuran Product distribution / selectivity; Reflux;

(3R)-1-azabicyclo[2.2.2]oct-3-yl 4-nitrophenyl carbonate (1243274-81-8) + (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline (22990-19-8, 96719-89-0, 118864-75-8) → solifenacin (242478-37-1)

Conditions	Yield
In N,N-dimethyl-formamide at 25 - 30℃; Product distribution / selectivity;

solifenacin succinate → solifenacin (242478-37-1)

Conditions	Yield
With ammonia In water; toluene pH=9 - 10;

sodium ethanolate (141-52-6) + chloroformic acid ethyl ester (541-41-3) + (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline (22990-19-8, 96719-89-0, 118864-75-8) + (R)-quinuclidin-3-ol (25333-42-0) → (1S,3'R)-2'-ethylquinuclidine-3'-yl-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate + solifenacin (242478-37-1)

Conditions	Yield
Stage #1: chloroformic acid ethyl ester; (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline With potassium carbonate In water; toluene at 10 - 25℃; for 2h; Stage #2: sodium ethanolate; (R)-quinuclidin-3-ol In N,N-dimethyl-formamide; toluene at 20℃; for 8h; Stage #3: With hydrogenchloride; potassium carbonate more than 3 stages;

succinic acid (110-15-6) + solifenacin (242478-37-1) → solifenacin succinate

Conditions	Yield
In toluene at 20 - 50℃; Product distribution / selectivity;	100%
In ethyl acetate at 20 - 80℃; for 10h;	94.2%
In ethyl acetate; acetone for 2h; Reflux;	91.9%

(1S)-3,4-dihydro-1-phenyl-2-(1H)-isoquinolinecarboxylic acid (3S)-1-azabicyclo[2.2.2]oct-3-yl ester (732228-02-3) + (3R)-1-azabicyclo[2.2.2]oct-3-yl (1R)-3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylate (740780-79-4) + succinic acid (110-15-6) + (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline (22990-19-8, 96719-89-0, 118864-75-8) + solifenacin (242478-37-1) → (1S)-3,4-dihydro-1-phenyl-2-(1H)-isoquinolinecarboxylic acid (3S)-1-azabicyclo[2.2.2]oct-3-yl ester succinate (862207-71-4) + (3R)-1-azabicyclo[2.2.2]oct-3-yl (1R)-3,4-dihydro-1-phenyl-2(1H)-isoquinoline carboxylate succinate (862207-70-3) + 1-(S)-phenyl-1,2,3,4-tetrahydroisoquinoline succinate + solifenacin succinate

Conditions	Yield
In isopropyl alcohol at 20℃;	A 0.33% B 0.17% C 0.07% D 89%

...Expand

succinic acid (110-15-6) + solifenacin (242478-37-1) → (1S)-(3R)-1-azabicyclo[2.2.2]oct-3-yl 3,4-dihydro-1-phenyl-2(1H)-isoquinoline carboxylate succinate

Conditions	Yield
In isopropyl alcohol at 20℃;	89%
In ethanol; ethyl acetate at 20℃; Reflux;
In ethanol at 70 - 75℃;

L-Tartaric acid (87-69-4) + solifenacin (242478-37-1) → (3R)-1-azabicyclo[2.2.2]oct-3-yl (1S)-3,4-dihydro-1-phenyl-2(1H)-isoquinoline carboxylate hydrogen L-tartrate (1035547-81-9)

Conditions	Yield
In methanol; isopropyl alcohol at 20℃;	89%

solifenacin (242478-37-1) → (1'S,3R)-3-[[(1'-phenyl-1',2',3',4'-tetrahydro-2'-isoquinolyl)carbonyl]oxy]quinuclidine 1-oxide (180272-28-0)

Conditions	Yield
With sodium hydrogencarbonate; 3-chloro-benzenecarboperoxoic acid In dichloromethane at 10 - 20℃; for 1h;	83%

(1S)-3,4-dihydro-1-phenyl-2-(1H)-isoquinolinecarboxylic acid (3S)-1-azabicyclo[2.2.2]oct-3-yl ester (732228-02-3) + (3R)-1-azabicyclo[2.2.2]oct-3-yl (1R)-3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylate (740780-79-4) + L-Tartaric acid (87-69-4) + solifenacin (242478-37-1) → (3S)-1-azabicyclo[2.2.2]oct-3-yl (1S)-3,4-dihydro-1-phenyl-2(1H)-isoquinoline carboxylate tartrate + (3R)-1-azabicyclo[2.2.2]oct-3-yl (1S)-3,4-dihydro-1-phenyl-2(1H)-isoquinoline carboxylate hydrogen L-tartrate (1035547-81-9) + (3R)-1-azabicyclo[2.2.2]oct-3-yl (1R)-3,4-dihydro-1-phenyl-2(1H)-isoquinoline carboxylate tartrate

Conditions	Yield
In methanol; isopropyl alcohol at 20℃;	A 0.6% B 79% C 1.1%

solifenacin (242478-37-1) → Solifenacin hydrochloride

Conditions	Yield
With hydrogenchloride In methanol; butanone at 20℃; Purification / work up;	63%
With hydrogenchloride In methanol; butanone at 20℃;	63%
With hydrogenchloride In ethanol; ethyl acetate
With hydrogenchloride In ethanol; water at 20℃; Product distribution / selectivity;

oxalic acid (144-62-7) + solifenacin (242478-37-1) → C2H2O4*C18H19NO2 + (S)-((R)-quinuclidin-3-yl) 1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate monooxalate + (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline oxalate + C2H2O4*C23H26N2O2 + C2H2O4*C23H26N2O2

Conditions	Yield
In ethanol

succinic acid (110-15-6) + solifenacin (242478-37-1) → (1S)-3,4-dihydro-1-phenyl-2-(1H)-isoquinolinecarboxylic acid (3S)-1-azabicyclo[2.2.2]oct-3-yl ester succinate (862207-71-4) + (3R)-1-azabicyclo[2.2.2]oct-3-yl (1R)-3,4-dihydro-1-phenyl-2(1H)-isoquinoline carboxylate succinate (862207-70-3) + solifenacin succinate

Conditions	Yield
In ethanol; ethyl acetate at 0 - 50℃; Product distribution / selectivity;

(3S)-1-azabicyclo[2.2.2]oct-3-yl (1R)-3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylate (774517-20-3) + solifenacin (242478-37-1) → (1S,3'S)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monohydrochloride + Solifenacin hydrochloride + (1R,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monohydrochloride + C18H19NO2*ClH + (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline hydrochloride

Conditions	Yield
With hydrogenchloride In ethanol; ethyl acetate Product distribution / selectivity;

Upstream product

• 180468-42-2 (S)-N-carboxylic acid ethyl ester-1-phenyl-1,2,3,4-tetrahydroisoquinoline 
• 25333-42-0 (R)-quinuclidin-3-ol 
• 180468-37-5 (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydro-isoquinoline-2-carboxylate hydrochloride 
• 180272-45-1 (R)-(-)-1-phenyl-1,2,3,4-tetrahydroisoquinoline 
• 881834-78-2 4-nitrophenyl-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate 
• 22990-19-8 1-phenyl-1,2,3,4-tetrahydroisoquinoline 
• 1300713-32-9 N-acetyl-(1R)-phenyl-1,2,3,4-tetrahydroisoquinoline 
• 5070-13-3 bis-(p-nitrophenyl) carbonate 
• 22990-19-8 (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline 
• 530-62-1 1,1'-carbonyldiimidazole 
• 20194-18-7 sodium phenyl-methanolate 
• 1251905-45-9 methyl (1S)-1-phenyl-3,4-dihydro-2(1H)-isoquinoline-carboxylate 
• 124-41-4 sodium methylate 
• 3278-14-6 N-phenethylbenzamide 

Downstream Products

• 180468-37-5 Solifenacin hydrochloride 
• 1035547-81-9 (3R)-1-azabicyclo[2.2.2]oct-3-yl (1S)-3,4-dihydro-1-phenyl-2(1H)-isoquinoline carboxylate hydrogen L-tartrate 
• 862207-71-4 (1S)-3,4-dihydro-1-phenyl-2-(1H)-isoquinolinecarboxylic acid (3S)-1-azabicyclo[2.2.2]oct-3-yl ester succinate 
• 862207-70-3 (3R)-1-azabicyclo[2.2.2]oct-3-yl (1R)-3,4-dihydro-1-phenyl-2(1H)-isoquinoline carboxylate succinate 
• 1262506-09-1 solifenacin succinate 

Relevant articles and documents

Synthesis process of solifenacin succinate

The invention discloses a synthesis process of solifenacin succinate, and relates to the technical field of medicines. The preparation method comprises the following steps: step 1, reacting (R)-quinuclidin-3-ol (B) with a reaction substance to generate (R)-quinuclidin-3-yl carbonochloridate (C); step 2, enabling (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline (A) to react with (R)-quinuclidin-3-yl carbonochloridate (C) to generate solifenacin (D); and step 3, using the solifenacin (D) to prepare the solifenacin succinate. After the technical scheme is adopted, the method has the beneficial effects that in the synthesis process, the problem of low conversion rate caused by direct ester exchange reaction is avoided, meanwhile, the probability of reversible reaction caused by nucleophilic intermediate products generated in the condensation process is also reduced, and the reaction is greatly promoted, so that the yield of solifenacin succinate is increased, the reaction conditions are mild, the operation is simple, the operation procedures are reduced, and the method is suitable for large-scale production.

Asymmetric synthesis method for preparation of solifenacin

The invention relates to an asymmetric synthesis method for preparation of solifenacin and specifically, discloses a preparation method of solifenacin. The method comprises that ortho-substituted aldehyde as a raw material undergoes a reaction under catalysis of rhodium and a chiral sulfoxide-olefin ligand to produce a key intermediate for high enantioselective addition, and the intermediate is further functionalized and cyclized to form solifenacin. The method is easy to operate, needs mild reaction conditions and has high efficiency and high selectivity.

A process for the preparation of new thorley that succinic acid

The invention relates to a method for preparing a solifenacin succinate ((3R)-1-azabicyclo [2.2.2] octane-3-yl (1S)-1-phenyl-3,4-dihydroisoquinoline-2-(1H)-carboxylate succinate). The method comprises the following steps: 1) preparing a compound (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline carboxylic acid ethyl ester of formula III from a compound (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline, serving as a raw material, of formula IV; 2) synthesizing a compound (3R)-1-azabicyclo [2.2.2] octane-3-yl (1S)-1-phenyl-3,4-dihydroisoquinoline-2-(1H)-carboxylate of formula II in an ionic liquid by using the compound (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline carboxylic acid ethyl ester of formula III; and 3) salifying the compound (3R)-1-azabicyclo [2.2.2] octane-3-yl (1S)-1-phenyl-3,4-dihydroisoquinoline-2-(1H)-carboxylate of formula II in an organic solvent to obtain the compound solifenacin succinate ((3R)-1-azabicyclo [2.2.2] octane-3-yl (1S)-1-phenyl-3,4-dihydroisoquinoline-2-(1H)-carboxylate succinate) of formula I. The preparation method has the advantages that the process is simple, the method is suitable for industrialized production, the yield of the product is high and the purity of the product is high.