99469-99-5

Basic information

• Product Name: 3-Ethoxy-4-ethoxycarbonyl phenylacetic acid
• Synonyms: 2-(4-(ETHOXYCARBONYL)-3-ETHOXYPHENYL)ACETIC ACID;3-Ethoxy-4-(ethoxycarbonyl)benzeneacetic acid;3-ethoxy-4-ethoxycarbonyl phenylacetic acid;4-ETHOXYCARBONYL-3-ETHOXYPHENYLACETIC ACID;BENZENEACETIC ACID, 3-ETHOXY-4-(ETHOXYCARBONYL)-;REPAGLINIDE RELATED COMPOUND B (50 MG) (3-ETHOXY-4-ETHOXYCARBONYL-PHENYLACETIC ACID);4-Ehtoxycarbonyl-3-Ehtoxyphynylacetic Acid;4-EHTOXYCARBONYL-3-EHTOXYPHYNYLACETIC ACID 98%
• CAS NO: 99469-99-5
• Molecular Formula: C13H16O5
• Molecular Weight: 252.26
• EINECS: 427-630-2
• Product Categories: Pharmaceutical material and intermeidates;Aromatic Phenylacetic Acids and Derivatives;Aromatics
• Mol File: 99469-99-5.mol
• Article Data: 9

Chemical Properties

• Melting Point: 78-80°C
• Boiling Point: 414.816 °C at 760 mmHg
• Flash Point: 155.936 °C
• Appearance: white to pale yellow solid
• Density: 1.191
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.5
• Storage Temp.: Refrigerator
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 3.96±0.10(Predicted)
• CAS DataBase Reference: 3-Ethoxy-4-ethoxycarbonyl phenylacetic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Ethoxy-4-ethoxycarbonyl phenylacetic acid(99469-99-5)
• EPA Substance Registry System: 3-Ethoxy-4-ethoxycarbonyl phenylacetic acid(99469-99-5)

Safety Data

• Hazard Codes: Xi
• Statements: 41
• Safety Statements: 26-39
• Hazardous Substances Data: 99469-99-5(Hazardous Substances Data)

Usage

Chemical Properties

White to Pale Yellow Solid

Uses

Different sources of media describe the Uses of 99469-99-5 differently. You can refer to the following data:
1. Repaglinide intermediate
2. Repaglinide intermediate.

InChI:InChI=1/C13H16O5/c1-4-16-12-8-10(18-9(3)14)6-7-11(12)13(15)17-5-2/h6-8H,4-5H2,1-3H3

Synthetic route

ethyl 2-ethoxy-4-(2-ethoxy-2-oxoethyl)benzoate (332347-69-0) → 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5)

Conditions	Yield
With hydrogenchloride In water pH=3; Large scale;	90.5%
Stage #1: ethyl 2-ethoxy-4-ethoxycarbonylmethyl-benzoate With sodium hydroxide; water In methanol at 10 - 15℃; for 1 - 2h; Stage #2: With hydrogenchloride In water at 0 - 5℃; pH=3 - 4;	77.8%
With sodium hydroxide In ethanol at 23 - 25℃; for 1.5h;	59%
With water; sodium hydroxide In ethanol at 30℃; for 1h;

2-ethoxy-4-methylbenzoic acid (88709-18-6) + carbonic acid dimethyl ester (616-38-6) → 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5)

Conditions	Yield
With lithium diisopropyl amide In tetrahydrofuran at -80 - -70℃; for 4h; Temperature;	86.2%

C16H22O5 → 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5)

Conditions	Yield
With hydrogenchloride In water pH=3;	78.1%

C17H24O5 → 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5)

Conditions	Yield
With hydrogenchloride In water pH=3;	77.7%

carbon dioxide (124-38-9) + ethyl 2-ethoxy-4-methyl-benzoate (88709-17-5) → 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5)

Conditions	Yield
Stage #1: With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -30℃; for 0.5h; Stage #2: ethyl 2-ethoxy-4-methyl-benzoate With N,N,N,N,N,N-hexamethylphosphoric triamide In tetrahydrofuran; hexane at -75℃; for 2h; Stage #3: carbon dioxide In tetrahydrofuran; hexane at -75 - 10℃; for 0.5h;	72.7%
Stage #1: ethyl 2-ethoxy-4-methyl-benzoate With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -75℃; Inert atmosphere; Industrial scale; Stage #2: carbon dioxide In tetrahydrofuran; hexane at -75℃; Industrial scale;	67%
Stage #1: With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -30℃; for 0.5h; Stage #2: ethyl 2-ethoxy-4-methyl-benzoate With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone In tetrahydrofuran; hexane at -75℃; for 2h; Stage #3: carbon dioxide In tetrahydrofuran; hexane at -75 - 20℃;	59.5%
Stage #1: ethyl 2-ethoxy-4-methyl-benzoate With N,N,N,N,N,N-hexamethylphosphoric triamide; n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 2h; Inert atmosphere; Stage #2: carbon dioxide In tetrahydrofuran; hexane at -78 - 10℃;	23%

ethyl 2-ethoxy-5-(2-oxo-2-(quinolin-8-ylamino)ethyl)benzoate → 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5)

Conditions	Yield
Stage #1: ethyl 2-ethoxy-5-(2-oxo-2-(quinolin-8-ylamino)ethyl)benzoate With ozone In dichloromethane at -78℃; Inert atmosphere; Stage #2: With copper dichloride In 1,4-dioxane; water at 100℃; for 1h; Inert atmosphere; Microwave irradiation;	42%

ethyl 4-(2-amino-2-oxoethyl)-2-ethoxybenzoate → 2-ethoxy-[4-(carboxymethyl)]benzoic acid (220438-80-2) + 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5)

Conditions	Yield
With hydrogenchloride; sodium nitrite at 35℃; for 2h;	A n/a B 39%

2-hydroxy-p-toluic acid (50-85-1) → 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5)

Conditions	Yield
Multi-step reaction with 5 steps 1: K2CO3 / diethyl ether / 30 h / 150 °C 2: N-bromosuccinimide, 2,2'-azo-bis-(isobutyronitril) / CCl4 3: 97 percent / aq. N-benzyl-tri-n-butylammonium-chloride / CH2Cl2 / 43 h / 20 °C 4: HCl / Heating 5: 59 percent / NaOH / ethanol / 1.5 h / 23 - 25 °C View Scheme
Multi-step reaction with 5 steps 1: K2CO3 / diethyl ether / 30 h / 150 °C 2: N-bromosuccinimide, 2,2'-azo-bis-(isobutyronitril) / CCl4 3: 97 percent / aq. N-benzyl-tri-n-butylammonium-chloride / CH2Cl2 / 43 h / 20 °C 4: aq. HCl / 1.5 h / 20 - 23 °C 5: 39 percent / aq. NaNO2, aq. HCl / 2 h / 35 °C View Scheme
Multi-step reaction with 2 steps 1.1: potassium carbonate / dimethyl sulfoxide / 10.5 h / 40 °C 2.1: diisopropylamine; n-butyllithium; N,N,N,N,N,N-hexamethylphosphoric triamide / tetrahydrofuran; hexane / 2 h / -78 °C / Inert atmosphere 2.2: -78 - 10 °C View Scheme
Multi-step reaction with 2 steps 1.1: potassium carbonate / dimethyl sulfoxide / 11 h / 40 °C 2.1: diisopropylamine; n-butyllithium; N,N,N,N,N,N-hexamethylphosphoric triamide / tetrahydrofuran; hexane / 2 h / -78 °C / Inert atmosphere 2.2: -78 - 10 °C View Scheme

ethyl 2-ethoxy-4-methyl-benzoate (88709-17-5) → 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: N-bromosuccinimide, 2,2'-azo-bis-(isobutyronitril) / CCl4 2: 97 percent / aq. N-benzyl-tri-n-butylammonium-chloride / CH2Cl2 / 43 h / 20 °C 3: HCl / Heating 4: 59 percent / NaOH / ethanol / 1.5 h / 23 - 25 °C View Scheme
Multi-step reaction with 4 steps 1: N-bromosuccinimide, 2,2'-azo-bis-(isobutyronitril) / CCl4 2: 97 percent / aq. N-benzyl-tri-n-butylammonium-chloride / CH2Cl2 / 43 h / 20 °C 3: aq. HCl / 1.5 h / 20 - 23 °C 4: 39 percent / aq. NaNO2, aq. HCl / 2 h / 35 °C View Scheme
Multi-step reaction with 2 steps 1: dihydrogen peroxide; copper dichloride; bis(diphenylphosphino)ethylamine / tetrahydrofuran / 10 h / 15001.5 Torr / Reflux 2: hydrogenchloride / water / pH 3 View Scheme
Multi-step reaction with 2 steps 1: tert.-butylhydroperoxide; palladium dichloride; depe / tetrahydrofuran / 20 h / 15001.5 Torr / Reflux 2: hydrogenchloride / water / pH 3 / Large scale View Scheme

ethyl 4-bromomethyl-2-ethoxy-benzoate (110017-07-7) → 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 97 percent / aq. N-benzyl-tri-n-butylammonium-chloride / CH2Cl2 / 43 h / 20 °C 2: HCl / Heating 3: 59 percent / NaOH / ethanol / 1.5 h / 23 - 25 °C View Scheme
Multi-step reaction with 3 steps 1: 97 percent / aq. N-benzyl-tri-n-butylammonium-chloride / CH2Cl2 / 43 h / 20 °C 2: aq. HCl / 1.5 h / 20 - 23 °C 3: 39 percent / aq. NaNO2, aq. HCl / 2 h / 35 °C View Scheme

ethyl 4-cyanomethyl-2-ethoxy-benzoate (99470-01-6) → 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: HCl / Heating 2: 59 percent / NaOH / ethanol / 1.5 h / 23 - 25 °C View Scheme
Multi-step reaction with 2 steps 1: aq. HCl / 1.5 h / 20 - 23 °C 2: 39 percent / aq. NaNO2, aq. HCl / 2 h / 35 °C View Scheme

ethyl 3-hydroxyphenylacetate (22446-38-4) → 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: acetic acid / 0.42 h / Reflux 1.2: 0.5 h / 0 °C 1.3: 5 h / 0 - 20 °C 2.1: potassium carbonate / acetonitrile / 0.5 h / 20 °C 2.2: 5 h / Reflux 3.1: sodium hydroxide; water / ethanol / 1 h / 30 °C View Scheme

3-hydroxyphenylacetic acid (621-37-4) → 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sulfuric acid / 2 h / Reflux 2.1: acetic acid / 0.42 h / Reflux 2.2: 0.5 h / 0 °C 2.3: 5 h / 0 - 20 °C 3.1: potassium carbonate / acetonitrile / 0.5 h / 20 °C 3.2: 5 h / Reflux 4.1: sodium hydroxide; water / ethanol / 1 h / 30 °C View Scheme

C13H16O5 → 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: oxalyl dichloride; thionyl chloride / dichloromethane; N,N-dimethyl-formamide / 2 h / 20 °C / Inert atmosphere; Schlenk technique 2.1: ozone / dichloromethane / -78 °C / Inert atmosphere 2.2: 1 h / 100 °C / Inert atmosphere; Microwave irradiation View Scheme

2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) + (1S)-3-methyl-1-(2-piperidin-1-ylphenyl)butan-1-amine (147769-93-5) → (S)-(+)-ethyl 2-ethoxy-4-<2-<<3-methyl-1-<2-(1-piperidinyl)phenyl>butyl>amino>-2-oxoethyl>-benzoate (147770-06-7)

Conditions	Yield
Stage #1: 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid With 1,1'-carbonyldiimidazole In dichloromethane Stage #2: (1S)-3-methyl-1-(2-piperidin-1-ylphenyl)butan-1-amine In dichloromethane Product distribution / selectivity;	93%
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate at 0 - 20℃; for 18.5h;	89.5%
With phenylboronic acid In toluene for 16 - 18h; Product distribution / selectivity; Heating / reflux;	89.6%

3-oxa-8-azabicyclo[3.2.1]octane hydrochloride + 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) → ethyl 4-(2-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-2-oxoethyl)-2-ethoxybenzoate

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;	93%

Cyclohexyl isocyanide (931-53-3) + C10H7NO2 + 1,4-phenylenediamine (106-50-3) + 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) → C66H72N6O12

Conditions	Yield
In methanol at 20℃; for 4.5h; Ugi Condensation;	90%

(S)-2-phenyl-1-[2-(piperidin-1-yl)phenyl]ethylamine + 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) → (S)-2-ethoxy-4-[2-({2-phenyl-1-[2-(piperidin-1-yl)phenyl]ethyl}amino)-2-oxoethyl]benzoic acid ethyl ester

Conditions	Yield
Stage #1: 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid With oxalyl dichloride In toluene for 3h; Stage #2: (S)-2-phenyl-1-[2-(piperidin-1-yl)phenyl]ethylamine With triethylamine In water; toluene for 2h;	87.2%

2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) + phenyl[2-(piperidin-1-yl)phenyl]methanamine (99469-98-4) → ethyl 2-ethoxy-4-[N-(α-phenyl-2-piperidino-benzyl)aminocarbonylmethyl]-benzoate (99469-91-7)

Conditions	Yield
	87%
	87%
With tetrachloromethane; triethylamine; triphenylphosphine In acetonitrile for 15h; Ambient temperature;	77%
	77%
	77%

Cyclohexyl isocyanide (931-53-3) + 4-methyl-benzaldehyde (104-87-0) + 1,4-phenylenediamine (106-50-3) + 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) → C62H74N4O10

Conditions	Yield
In methanol at 20℃; for 5h; Ugi Condensation;	87%

Cyclohexyl isocyanide (931-53-3) + terephthalaldehyde, (623-27-8) + p-toluidine (106-49-0) + 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) → C62H74N4O10

Conditions	Yield
In methanol at 20℃; for 5.5h; Ugi Condensation;	86%

2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) + (S)-1-(2-piperidino-phenyl)-3-methyl-1-butylamine (108157-52-4) → ethyl 2-ethoxy-4-<2-<<3-methyl-1-<2-(1-piperidinyl)phenyl>butyl>amino>-2-oxoethyl>-benzoate (108175-51-5)

Conditions	Yield
With tetrachloromethane; triethylamine; triphenylphosphine In acetonitrile for 15h; Ambient temperature;	85%
With triethylamine; triphenylphosphine In tetrachloromethane; water; ethyl acetate; acetonitrile

1-(6-chloro-2-piperidino-phenyl)-1-butylamine + 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) → ethyl 2-ethoxy-4-[N-{1-(6-chloro-2-piperidino-phenyl)-1-butyl}-aminocarbonylmethyl]-benzoate

Conditions	Yield
	85%
	85%

Cyclohexyl isocyanide (931-53-3) + terephthalaldehyde, (623-27-8) + aniline (62-53-3) + 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) → diethyl-4,4'-(2,2'-(1,1'-(1,4-phenylene)bis(2-(cyclohexylamino)-2-oxoethane-1,1-diyl))bis (phenylazanediyl)bis(2-oxoethane-2,1-diyl))bis(2-ethoxybenzoate)

Conditions	Yield
In methanol at 20℃; for 6h; Ugi Condensation;	85%

pyrrolidine (123-75-1) + 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) → ethyl 2-ethoxy-4-(2-oxo-2-(pyrrolidin-1-yl)ethyl)benzoate

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;	83%

Cyclohexyl isocyanide (931-53-3) + benzaldehyde (100-52-7) + 1,4-phenylenediamine (106-50-3) + 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) → diethyl-4,4'-(2,2'-(1,4-phenylenebis((2-(cyclohexylamino)-2-oxo-1-sphenylethyl)azanediyl)) bis(2-oxoethane-2,1-diyl))bis(2-ethoxybenzoate)

Conditions	Yield
In methanol at 20℃; for 5.15h; Ugi Condensation;	83%

Cyclohexyl isocyanide (931-53-3) + terephthalaldehyde, (623-27-8) + 4-chloro-aniline (106-47-8) + 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) → C60H68Cl2N4O10

Conditions	Yield
In methanol at 20℃; for 5h; Ugi Condensation;	82%

Cyclohexyl isocyanide (931-53-3) + m-tolyl aldehyde (620-23-5) + 1,4-phenylenediamine (106-50-3) + 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) → C62H74N4O10

Conditions	Yield
In methanol at 20℃; for 6h; Ugi Condensation;	82%

2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) + 1-(2-piperidino-phenyl)-butylamine (99469-97-3) → ethyl 2-ethoxy-4-<2-<<1-<2-(1-piperidinyl)phenyl>butyl>amino>-2-oxoethyl>-benzoate (99469-89-3)

Conditions	Yield
With tetrachloromethane; triethylamine; triphenylphosphine In acetonitrile for 15h; Ambient temperature;	81%
With triethylamine; triphenylphosphine In tetrachloromethane; water; ethyl acetate; acetonitrile
With 1,1'-carbonyldiimidazole In tetrahydrofuran
With 1,1'-carbonyldiimidazole In tetrahydrofuran

Cyclohexyl isocyanide (931-53-3) + 4-chlorobenzaldehyde (104-88-1) + 1,4-phenylenediamine (106-50-3) + 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) → C60H68Cl2N4O10

Conditions	Yield
In methanol at 20℃; for 5.5h; Ugi Condensation;	81%

2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) + 1-(5-chloro-2-piperidino-phenyl)-propylamine → ethyl 2-ethoxy-4-<2-<<1-<5-chloro-2-(1-piperidinyl)phenyl>propyl>amino>-2-oxoethyl>-benzoate (219922-19-7)

Conditions	Yield
	80%
	80%
With tetrachloromethane; triethylamine; triphenylphosphine In acetonitrile for 15h; Ambient temperature;	51%

2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) + 2-(5-chloro-2-piperidino-phenyl)-2-propylamine → ethyl 2-ethoxy-4-<2-<<1-<5-chloro-2-(1-piperidinyl)phenyl>propyl>amino>-2-oxoethyl>-benzoate

Conditions	Yield
With tetrachloromethane; triethylamine; triphenylphosphine In acetonitrile for 15h; Ambient temperature;	80%

2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) + 1-(2-piperidino-phenyl)-heptylamine (219921-62-7) → ethyl 2-ethoxy-4-<2-<<1-<2-(1-piperidinyl)phenyl>heptyl>amino>-2-oxoethyl>-benzoate (219922-26-6)

Conditions	Yield
With tetrachloromethane; triethylamine; triphenylphosphine In acetonitrile for 15h; Ambient temperature;	80%
	79%
	79%

Cyclohexyl isocyanide (931-53-3) + terephthalaldehyde, (623-27-8) + 1-amino-3-methylbenzene (108-44-1) + 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) → C62H74N4O10

Conditions	Yield
In methanol at 20℃; for 6h; Ugi Condensation;	78%

2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) → C12H15(2)HO3

Conditions	Yield
With 2,4,6-trimethyl-pyridine; 2,4,6-Triisopropylthiophenol; water-d2; 9-(2-mesityl)-10-methylacridinium perchlorate In dichloromethane at 20℃; Irradiation;	78%

2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) + (±)-2-phenyl-1-[2-(piperidin-1-yl)phenyl]ethylamine (107362-46-9) → ethyl 2-ethoxy-4-<2-<<2-phenyl-1-<2-(1-piperidinyl)phenyl>ethyl>amino>-2-oxoethyl>-benzoate (107362-11-8)

Conditions	Yield
With tetrachloromethane; triethylamine; triphenylphosphine In acetonitrile for 15h; Ambient temperature;	72%

1-(2-piperidino-phenyl)-ethylamine (89606-11-1, 767583-77-7, 779992-28-8) + 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) → ethyl 2-ethoxy-4-<2-<<1-<2-(1-piperidinyl)phenyl>ethyl>amino>-2-oxoethyl>-benzoate (219922-18-6)

Conditions	Yield
With tetrachloromethane; triethylamine; triphenylphosphine In acetonitrile for 15h; Ambient temperature;	70%

2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) + 3-methyl-1-(2-piperidino-phenyl)-3-butenylamine glutarate → ethyl 2-ethoxy-4-<2-<<3-methyl-1-<2-(1-piperidinyl)phenyl>3-buten-1-yl>amino>-2-oxoethyl>-benzoate (219922-24-4)

Conditions	Yield
With dicyclohexyl-carbodiimide In toluene for 2h; Ambient temperature;	70%

Cyclohexyl isocyanide (931-53-3) + 4-fluorobenzaldehyde (459-57-4) + 1,4-phenylenediamine (106-50-3) + 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid (99469-99-5) → C60H68F2N4O10

Conditions	Yield
In methanol at 20℃; for 6h; Ugi Condensation;	70%

Upstream product

• 332347-69-0 ethyl 2-ethoxy-4-ethoxycarbonylmethyl-benzoate 
• 88709-17-5 ethyl 2-ethoxy-4-methyl-benzoate 
• 88709-18-6 2-ethoxy-4-methylbenzoic acid 
• 616-38-6 carbonic acid dimethyl ester 
• 621-37-4 m-hydroxyphenylacetic acid 
• 22446-38-4 ethyl 3-hydroxyphenylacetate 
• 124-38-9 carbon dioxide 
• 99470-01-6 ethyl 4-cyanomethyl-2-ethoxy-benzoate 
• 110017-07-7 ethyl 4-bromomethyl-2-ethoxy-benzoate 
• 50-85-1 2-hydroxy-p-toluic acid 

Downstream Products

• 219922-30-2 ethyl 2-ethoxy-4-<2-<<2-cycloheptyl-1-<2-(1-piperidinyl)phenyl>ethyl>amino>-2-oxoethyl>-benzoate 

Relevant articles and documents

Synthesis method of 3-ethoxy-4-ethoxycarbonyl phenylacetic acid

The invention relates to a synthesis method of 3-ethoxy-4-ethoxycarbonyl phenylacetic acid, and belongs to the technical field of medicine synthesis. In order to solve the problems of long reaction route and low yield in the prior art, the invention provides the synthesis method of 3-ethoxy-4-ethoxycarbonyl phenylacetic acid, which comprises the following steps: under the actions of a catalytic amount of phase transfer catalyst and cocatalyst, carrying out etherification and esterification reaction on 4-methylsalicylic acid and diethyl carbonate in a water-insoluble solvent to obtain a corresponding intermediate is obtained, in the presence of lithium diisopropylamide, carrying out methylation reaction on the intermediate and dimethyl carbonate or diethyl carbonate at the temperature of -50 DEG C or below, and carrying out acid regulation treatment to control the pH value of the system to be 3.5 or below, thereby obtaining the corresponding product compound 3-ethoxy-4-ethoxycarbonylphenylacetic acid shown in the formula III. According to the method, the operation of each step of reaction post-treatment is simple and easy, the method has the advantage of short reaction route, and the yield of the final product is high.

Bridging C?H Activation: Mild and Versatile Cleavage of the 8-Aminoquinoline Directing Group

8-Aminoquinoline has emerged as one of the most powerful bidentate directing groups in history of C?H activation within the last decade. However, cleavage of its robust amide bond has shown to be challenging in several cases, thus jeopardizing the general synthetic utility of the method. To overcome this limitation, we herein report a simple oxidative deprotection protocol. This transformation rapidly converts the robust amide to a labile imide, allowing subsequent cleavage in a simple one-pot fashion to rapidly access carboxylic acids or amides as final products.

TETRAHYDROISOQUINOLINE DERIVED PRMT5-INHIBITORS

A compound of formula I wherein: n is 1 or 2: p is 0 or 1; R1 is optionally one or more halo or methyl groups; R2a and R2b are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R2c and R2d are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R3a and R3b are independently selected from H and Me; R4 is either H or Me; R5 is either H or Me; R6a and R6b are independently selected from H and Me; A is either (i) optionally substituted phenyl; (ii) optionally substituted naphthyl; or (iii) optionally substituted C5-12 heteroaryl.