173140-90-4

Usage

Uses

Used in Organic Synthesis:
2(1H)-Quinolinone, 5-(2R)-oxiranyl-8-(phenylmethoxy)is used as an organic synthesis intermediate due to its unique structural features. Its oxiranyl and phenylmethoxy groups can participate in various chemical reactions, such as ring-opening reactions, nucleophilic substitutions, and electrophilic aromatic substitutions, making it a versatile building block for the synthesis of more complex organic molecules.
Used in Pharmaceutical Industry:
As a pharmaceutical intermediate, 2(1H)-Quinolinone, 5-(2R)-oxiranyl-8-(phenylmethoxy)plays a crucial role in the development of new drugs. Its unique chemical properties allow it to be used as a starting material or a key intermediate in the synthesis of various pharmaceutical compounds, particularly those targeting specific biological receptors or enzymes.
Used in Laboratory Research and Development:
2(1H)-Quinolinone, 5-(2R)-oxiranyl-8-(phenylmethoxy)is also utilized in laboratory research and development processes. Researchers can use 2(1H)-Quinolinone, 5-(2R)-oxiranyl-8-(phenylmethoxy)- to explore new reaction pathways, develop novel synthetic methods, and investigate its potential applications in various fields, such as materials science, medicinal chemistry, and chemical biology.
Used in Chemical Production Process:
In the chemical production process, 2(1H)-Quinolinone, 5-(2R)-oxiranyl-8-(phenylmethoxy)serves as an essential intermediate for the large-scale synthesis of various chemicals and pharmaceuticals. Its unique reactivity and structural features make it a valuable component in the manufacturing of specialty chemicals, fine chemicals, and active pharmaceutical ingredients.

Synthesis

A 5 liter flask equipped with a mechanical stirrer, thermometer, and refluxing condenser was charged with 8-benzyloxy-5-[(R)-(2-bromo-1-hydroxyethyl)]-carbostyriI (70gms/0.187 moles), potassium carbonate (74 gmsl 0.536 moles), acetone (3.5 liters) and water (35 ml). The resulting slurry 'was heated to reflux and maintained for 2% hours. After completion of reaction, the hot mass was filtered on hylo bed to remove inorganics. The residue was slurried in dichloromethane (200 ml) and filtered on hyflo bed. The filtrates were combined together and concentrated under vacuum completely. The residue was dissolved. in dichloromethane (500ml) and filtered on hyflo bed to remove traces of insolubles and washed with dichloromethane(100 ml). The clear filtrate was distilled completely to obtain residue. The residue was charged with methanol (70 ml), stirred and heated to 50°C for 30 minutes. The slurry obtained was cooled to 25-30°C,chilled to 0- 5°C, stirred for 1 hour. The resulting solid was isolated by filtration, washed with methanol (30ml), followed by diisopropylether (100ml) and dried under vacuum at 60-65 °C for 10-12 hours to yield 40-41 gms of 8-benzyloxy- 5-(R)-oxiranylcarbostyril.

Synthetic route

8-(phenylmethoxy)-5-((R)-2-chloro-1-hydroxy-ethyl)-(1H)-quinolin-2-one → (R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4)

Conditions	Yield
With potassium carbonate In water; acetone for 5 - 10h; Heating / reflux;
With potassium carbonate In water; acetone for 5 - 10h; Heating / reflux;
With potassium carbonate In water; butanone Product distribution / selectivity; Heating / reflux;
With potassium carbonate In water; acetone Product distribution / selectivity; Heating / reflux;

8-(benzyloxy)-5-[(1R)-2-bromo-1-hydroxyethyl]quinolin-2(1H)-one (530084-79-8) → (R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4)

Conditions	Yield
With potassium carbonate In water; acetone for 2.5h; Product distribution / selectivity; Heating / reflux;

8-benzyloxy-5-(2-bromoacetyl)-1H-quinolin-2-one (100331-89-3) → (R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4)

Conditions	Yield
Stage #1: 8-benzyloxy-5-(2-bromoacetyl)-1H-quinolin-2-one With dimethylsulfide borane complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole In tetrahydrofuran; toluene at 0 - 2℃; for 1.75h; Stage #2: With piperidine; water In tetrahydrofuran; toluene at 0 - 2℃; for 1h; Product distribution / selectivity;
Multi-step reaction with 2 steps 1.1: dimethylsulfide borane complex / (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran; toluene / 3.25 - 3.33 h / 0 - 2 °C 1.2: 0.25 - 0.33 h 2.1: potassium carbonate / water; acetone / 2.5 h / Heating / reflux View Scheme

8-quinolinol (148-24-3) → (R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: 1,2-dichloro-ethane / 2.25 - 2.33 h / 30 °C 1.2: 15.25 - 16.33 h / 25 - 70 °C 1.3: 0.25 - 0.33 h / 0 - 30 °C 2.1: hydrogenchloride; water / 0.25 - 0.33 h 3.1: potassium carbonate / acetone / 14 h / Heating / reflux 4.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 3.5 h / 20 - 30 °C 5.1: acetic anhydride / 2 h / 25 - 40 °C 6.1: boron trifluoride diethyl etherate / dichloromethane / Heating / reflux 6.2: 4.5 h / Heating / reflux 6.3: 30 °C / pH 8 - 9 7.1: dimethylsulfide borane complex / (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran; toluene / 1.75 h / 0 - 2 °C 7.2: 1 h / 0 - 2 °C View Scheme
Multi-step reaction with 8 steps 1.1: 1,2-dichloro-ethane / 2.25 - 2.33 h / 30 °C 1.2: 15.25 - 16.33 h / 25 - 70 °C 1.3: 0.25 - 0.33 h / 0 - 30 °C 2.1: hydrogenchloride; water / 0.25 - 0.33 h 3.1: potassium carbonate / acetone / 14 h / Heating / reflux 4.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 3.5 h / 20 - 30 °C 5.1: acetic anhydride / 2 h / 25 - 40 °C 6.1: boron trifluoride diethyl etherate / dichloromethane / Heating / reflux 6.2: 4.5 h / Heating / reflux 6.3: 30 °C / pH 8 - 9 7.1: dimethylsulfide borane complex / (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran; toluene / 3.25 - 3.33 h / 0 - 2 °C 7.2: 0.25 - 0.33 h 8.1: potassium carbonate / water; acetone / 2.5 h / Heating / reflux View Scheme

5-acetyl-8-hydroxyquinoline (2598-31-4) → (R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: potassium carbonate / acetone / 14 h / Heating / reflux 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 3.5 h / 20 - 30 °C 3.1: acetic anhydride / 2 h / 25 - 40 °C 4.1: boron trifluoride diethyl etherate / dichloromethane / Heating / reflux 4.2: 4.5 h / Heating / reflux 4.3: 30 °C / pH 8 - 9 5.1: dimethylsulfide borane complex / (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran; toluene / 1.75 h / 0 - 2 °C 5.2: 1 h / 0 - 2 °C View Scheme
Multi-step reaction with 6 steps 1.1: potassium carbonate / acetone / 14 h / Heating / reflux 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 3.5 h / 20 - 30 °C 3.1: acetic anhydride / 2 h / 25 - 40 °C 4.1: boron trifluoride diethyl etherate / dichloromethane / Heating / reflux 4.2: 4.5 h / Heating / reflux 4.3: 30 °C / pH 8 - 9 5.1: dimethylsulfide borane complex / (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran; toluene / 3.25 - 3.33 h / 0 - 2 °C 5.2: 0.25 - 0.33 h 6.1: potassium carbonate / water; acetone / 2.5 h / Heating / reflux View Scheme

1-(8-benzyloxyquinolin-5-yl)ethanone (26872-48-0) → (R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 3.5 h / 20 - 30 °C 2.1: acetic anhydride / 2 h / 25 - 40 °C 3.1: boron trifluoride diethyl etherate / dichloromethane / Heating / reflux 3.2: 4.5 h / Heating / reflux 3.3: 30 °C / pH 8 - 9 4.1: dimethylsulfide borane complex / (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran; toluene / 1.75 h / 0 - 2 °C 4.2: 1 h / 0 - 2 °C View Scheme
Multi-step reaction with 5 steps 1.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 3.5 h / 20 - 30 °C 2.1: acetic anhydride / 2 h / 25 - 40 °C 3.1: boron trifluoride diethyl etherate / dichloromethane / Heating / reflux 3.2: 4.5 h / Heating / reflux 3.3: 30 °C / pH 8 - 9 4.1: dimethylsulfide borane complex / (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran; toluene / 3.25 - 3.33 h / 0 - 2 °C 4.2: 0.25 - 0.33 h 5.1: potassium carbonate / water; acetone / 2.5 h / Heating / reflux View Scheme

5-Acetyl-8-benzyloxyquinoline-N-oxide (100331-93-9) → (R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: acetic anhydride / 2 h / 25 - 40 °C 2.1: boron trifluoride diethyl etherate / dichloromethane / Heating / reflux 2.2: 4.5 h / Heating / reflux 2.3: 30 °C / pH 8 - 9 3.1: dimethylsulfide borane complex / (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran; toluene / 1.75 h / 0 - 2 °C 3.2: 1 h / 0 - 2 °C View Scheme
Multi-step reaction with 4 steps 1.1: acetic anhydride / 2 h / 25 - 40 °C 2.1: boron trifluoride diethyl etherate / dichloromethane / Heating / reflux 2.2: 4.5 h / Heating / reflux 2.3: 30 °C / pH 8 - 9 3.1: dimethylsulfide borane complex / (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran; toluene / 3.25 - 3.33 h / 0 - 2 °C 3.2: 0.25 - 0.33 h 4.1: potassium carbonate / water; acetone / 2.5 h / Heating / reflux View Scheme

5-acetyl-8-hydroxyquinoline hydrochloride (57434-96-5) → (R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: hydrogenchloride; water / 0.25 - 0.33 h 2.1: potassium carbonate / acetone / 14 h / Heating / reflux 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 3.5 h / 20 - 30 °C 4.1: acetic anhydride / 2 h / 25 - 40 °C 5.1: boron trifluoride diethyl etherate / dichloromethane / Heating / reflux 5.2: 4.5 h / Heating / reflux 5.3: 30 °C / pH 8 - 9 6.1: dimethylsulfide borane complex / (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran; toluene / 1.75 h / 0 - 2 °C 6.2: 1 h / 0 - 2 °C View Scheme
Multi-step reaction with 7 steps 1.1: hydrogenchloride; water / 0.25 - 0.33 h 2.1: potassium carbonate / acetone / 14 h / Heating / reflux 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 3.5 h / 20 - 30 °C 4.1: acetic anhydride / 2 h / 25 - 40 °C 5.1: boron trifluoride diethyl etherate / dichloromethane / Heating / reflux 5.2: 4.5 h / Heating / reflux 5.3: 30 °C / pH 8 - 9 6.1: dimethylsulfide borane complex / (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran; toluene / 3.25 - 3.33 h / 0 - 2 °C 6.2: 0.25 - 0.33 h 7.1: potassium carbonate / water; acetone / 2.5 h / Heating / reflux View Scheme

benzyl bromide (100-39-0) → (R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: potassium carbonate / acetone / 14 h / Heating / reflux 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 3.5 h / 20 - 30 °C 3.1: acetic anhydride / 2 h / 25 - 40 °C 4.1: boron trifluoride diethyl etherate / dichloromethane / Heating / reflux 4.2: 4.5 h / Heating / reflux 4.3: 30 °C / pH 8 - 9 5.1: dimethylsulfide borane complex / (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran; toluene / 1.75 h / 0 - 2 °C 5.2: 1 h / 0 - 2 °C View Scheme
Multi-step reaction with 6 steps 1.1: potassium carbonate / acetone / 14 h / Heating / reflux 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 3.5 h / 20 - 30 °C 3.1: acetic anhydride / 2 h / 25 - 40 °C 4.1: boron trifluoride diethyl etherate / dichloromethane / Heating / reflux 4.2: 4.5 h / Heating / reflux 4.3: 30 °C / pH 8 - 9 5.1: dimethylsulfide borane complex / (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran; toluene / 3.25 - 3.33 h / 0 - 2 °C 5.2: 0.25 - 0.33 h 6.1: potassium carbonate / water; acetone / 2.5 h / Heating / reflux View Scheme

5-acetyl-8-benzyloxy-1H-quinolin-2-one (93609-84-8) → (R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: boron trifluoride diethyl etherate / dichloromethane / Heating / reflux 1.2: 4.5 h / Heating / reflux 1.3: 30 °C / pH 8 - 9 2.1: dimethylsulfide borane complex / (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran; toluene / 1.75 h / 0 - 2 °C 2.2: 1 h / 0 - 2 °C View Scheme
Multi-step reaction with 3 steps 1.1: boron trifluoride diethyl etherate / dichloromethane / Heating / reflux 1.2: 4.5 h / Heating / reflux 1.3: 30 °C / pH 8 - 9 2.1: dimethylsulfide borane complex / (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran; toluene / 3.25 - 3.33 h / 0 - 2 °C 2.2: 0.25 - 0.33 h 3.1: potassium carbonate / water; acetone / 2.5 h / Heating / reflux View Scheme

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + N-benzyltyramine (52447-50-4) → C33H32N2O4 (630127-17-2)

Conditions	Yield
In toluene at 100℃; for 12h;	88%

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + D-glucoheptonic acid (87-74-1) + 5,6-diethyl-2,3-dihydro-1H-inden-2-amine (312753-70-1) → 5-[(R)-2-(5,6-diethylindan-2-yl-amino)-1-hydroxyethyl]-8-benzyloxy-(1H)-quinolin-2-one glucoheptonic acid

Conditions	Yield
Stage #1: (R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone; 5,6-diethyl-2,3-dihydro-1H-inden-2-amine at 90℃; for 5h; Stage #2: D-glucoheptonic acid In ethanol at 60℃; for 0.0833333h;	81.2%

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + 5,6-diethyl-2,3-dihydro-1H-inden-2-amine (312753-70-1) + p-(acetylamino)benzoic acid (556-08-1) → 5-[(R)-2-(5,6-diethylindan-2-yl-amino)-1-hydroxyethyl]-8-benzyloxy-(1H)-quinolin-2-one 4-acetamidobenzoic acid

Conditions	Yield
Stage #1: (R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone; 5,6-diethyl-2,3-dihydro-1H-inden-2-amine at 100℃; for 5h; Stage #2: p-(acetylamino)benzoic acid In ethanol at 60℃; for 0.0833333h;	80.4%

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + 5,6-diethyl-2,3-dihydro-1H-inden-2-amine (312753-70-1) + D-galacturonic acid (685-73-4) → 5-[(R)-2-(5,6-diethylindan-2-yl-amino)-1-hydroxyethyl]-8-benzyloxy-(1H)-quinolin-2-one galacturonic acid

Conditions	Yield
Stage #1: (R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone; 5,6-diethyl-2,3-dihydro-1H-inden-2-amine In butanone at 70℃; for 6h; Stage #2: D-galacturonic acid In ethanol; butanone at 60℃; for 0.0833333h;	79.8%

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + 5,6-diethyl-2,3-dihydro-1H-inden-2-amine (312753-70-1) + meso-tartaric acid (147-73-9) → 5-[(R)-2-(5,6-diethylindan-2-yl-amino)-1-hydroxyethyl]-8-benzyloxy-(1H)-quinolin-2-one tartaric acid

Conditions	Yield
Stage #1: (R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone; 5,6-diethyl-2,3-dihydro-1H-inden-2-amine In cyclohexanone at 80℃; for 6h; Stage #2: meso-tartaric acid In ethanol; cyclohexanone at 60℃; for 0.0833333h;	78.3%

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + 5,6-diethyl-2,3-dihydro-1H-inden-2-amine (312753-70-1) + 4-methoxybenzoic acid (100-09-4) → 5-[(R)-2-(5,6-diethylindan-2-ylamino)-1-hydroxyethyl]-8-phenylmethoxy-(1H)-quinolin-2-one p-methoxybenzoic acid

Conditions	Yield
Stage #1: (R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone; 5,6-diethyl-2,3-dihydro-1H-inden-2-amine In dimethyl sulfoxide at 110℃; for 7h; Stage #2: 4-methoxybenzoic acid In ethanol; dimethyl sulfoxide at 60℃;	70.1%

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + 5,6-diethyl-2,3-dihydro-1H-inden-2-amine (312753-70-1) → 8-(benzyloxy)-5-(1-(5,6-diethyl-2,3-dihydro-1H-inden-2-ylamino)-2-hydroxyethyl)quinolin-2(1H)-one + (R)-5- [2-(5,6-diethylindan-2-ylamino)-1-hydroxyethyl]-8-benzyloxy-1H-quinolin-2-one hydrochloride + C49H49N3O6

Conditions	Yield
In diethylene glycol dimethyl ether at 110℃; for 15h; Heating / reflux;	A 7.8% B 68.7% C 12.4%

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + 5,6-diethyl-2,3-dihydro-1H-inden-2-amine (312753-70-1) → Indacaterol hydrochloride + C31H34N2O3*ClH + C49H49N3O6*ClH

Conditions	Yield
Stage #1: (R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone; 5,6-diethyl-2,3-dihydro-1H-inden-2-amine In diethylene glycol dimethyl ether at 110℃; for 15h; Stage #2: With hydrogenchloride Product distribution / selectivity;	A 68.7% B 7.8% C 12.4%

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + benzyl-(4,5,6,7-tetramethyl-indan-2yl)-1-amine (312753-89-2) → C38H40N2O3 (312754-35-1)

Conditions	Yield
In butan-1-ol at 110℃; for 22h;	67%

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + 5,6-diethyl-2,3-dihydro-1H-inden-2-amine (312753-70-1) + p-Toluic acid (99-94-5) → 5-[(R)-2-(5,6-diethylindan-2-ylamino)-1-hydroxyethyl]-8-phenylmethoxy-(1H)-quinolin-2-one p-toluic acid

Conditions	Yield
Stage #1: (R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone; 5,6-diethyl-2,3-dihydro-1H-inden-2-amine In dimethyl sulfoxide at 110℃; for 7h; Stage #2: p-Toluic acid In ethanol; dimethyl sulfoxide at 60℃;	63.5%

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + 5,6-diethyl-2,3-dihydro-1H-inden-2-amine (312753-70-1) + 4-nitro-benzoic acid (62-23-7) → 5-[(R)-2-(5,6-diethylindan-2-ylamino)-1-hydroxyethyl]-8-phenylmethoxy-(1H)-quinolin-2-one p-nitrobenzoic acid

Conditions	Yield
Stage #1: (R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone; 5,6-diethyl-2,3-dihydro-1H-inden-2-amine In dimethyl sulfoxide at 110℃; for 7h; Stage #2: 4-nitro-benzoic acid In ethanol; dimethyl sulfoxide at 60℃;	63%

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + 5,6-Dimethoxy-2-indanylamine (83598-55-4) → 8-benzyloxy-5-[(R)-1-hydroxy-2-(5,6-dimethoxyindan-2-ylamino)-ethyl]-1H-quinolin-2-one (1225285-25-5)

Conditions	Yield
In butan-1-ol at 110℃; under 760.051 Torr; for 1h; Inert atmosphere; Microwave irradiation; regioselective reaction;	36%

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + 2-amino-5,6-di-n-butylindan (312753-59-6) → 8-benzyloxy-5-[(R)-1-hydroxy-2-(5,6-di-n-butylindan-2-ylamino)-ethyl]-1H-quinolin-2-one (1225285-24-4)

Conditions	Yield
In butan-1-ol at 110℃; under 760.051 Torr; for 1h; Inert atmosphere; Microwave irradiation; regioselective reaction;	34%

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + C13H19N (789489-14-1) → C31H34N2O3

Conditions	Yield
In N,N-dimethyl acetamide at 180℃; for 0.133333h; Microwave irradiation;	31%

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + 2,3-dihydro-1H-inden-2-amine (2975-41-9) → 8-benzyloxy-5-[(R)-1-hydroxy-2-(indan-2-ylamino)-ethyl]-1H-quinolin-2-one (1225285-21-1)

Conditions	Yield
In butan-1-ol at 110℃; under 760.051 Torr; for 1h; Inert atmosphere; Microwave irradiation; regioselective reaction;	30%

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + 5,6-diethyl-2-methyl-indan-2-ylamine (312754-11-3) → C32H36N2O3 (312754-19-1)

Conditions	Yield
In butan-1-ol at 100℃; for 1.25h; Microwave irradiation;	30%

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + benzyl bromide (100-39-0) → C25H21NO3

Conditions	Yield
With tetra-(n-butyl)ammonium iodide; potassium hydroxide In toluene at 50℃; for 6h;	30%

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + 5,6-diethyl-2,3-dihydro-1H-inden-2-amine (312753-70-1) → (R)-8-(benzyloxy)-5-[2-[(5,6-diethyl-2,3-dihydro-1H-indole-2-yl)amino]-1-hydroxyethyl]quinolin-2(1H)-one (435273-75-9)

Conditions	Yield
In butan-1-ol at 110℃; under 760.051 Torr; for 1h; Inert atmosphere; Microwave irradiation; regioselective reaction;	28%
In diethylene glycol dimethyl ether at 108 - 114℃; Inert atmosphere;
In dimethyl sulfoxide for 18h; Reflux; Large scale;
In butan-1-ol at 120℃; for 6h; Temperature;

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + 2-amino-5,6-dimethylindan (162752-07-0) → 8-benzyloxy-5-[(R)-1-hydroxy-2-(5,6-dimethylindan-2-ylamino)-ethyl]-1H-quinolin-2-one (1225285-22-2)

Conditions	Yield
In butan-1-ol at 110℃; under 760.051 Torr; for 1h; Inert atmosphere; Microwave irradiation; regioselective reaction;	27%

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + 2-amino-4,7-diethylindan (312753-56-3) → 8-hydroxy-5-[(R)-1-hydroxy-2-(4,7-diethylindan-2-ylamino)-ethyl]-1H-quinolin-2-one (1225285-26-6)

Conditions	Yield
In butan-1-ol at 110℃; under 760.051 Torr; for 1h; Inert atmosphere; Microwave irradiation; regioselective reaction;	22%

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + 2-amino-5,6-di-n-propylindan (312753-60-9) → 8-benzyloxy-5-[(R)-1-hydroxy-2-(5,6-di-n-propylindan-2-ylamino)-ethyl]-1H-quinolin-2-one (1225285-23-3)

Conditions	Yield
In butan-1-ol at 110℃; under 760.051 Torr; for 1h; Inert atmosphere; Microwave irradiation; regioselective reaction;	21%

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + C16H29NSi → 8-benzyloxy-5-[R-2-(5,6-diethyl-2,3,4,7-tetrahydro-1H-inden-2-ylamino)-1-hydroxy-ethyl]-1H-quinolin-2-one (774222-38-7)

Conditions	Yield
In N,N-dimethyl-formamide at 80℃; for 36h;	21%

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + benzylamine (100-46-9) → 8-benzyloxy-5-[(R)-2-benzylamino-1-hydroxyethyl]-(1H)-quinolin-2-one (662111-65-1)

Conditions	Yield
at 150℃; for 0.25h; Microwave rewactor;
at 150℃; for 0.25h; Microwave oven;

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + C26H26N4O2S → C44H41N5O5S (1064594-84-8)

Conditions	Yield
In dichloromethane; isopropyl alcohol at 70℃; for 40h; Heating / reflux;

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + C25H29N3O3S → C43H44N4O6S (1064594-80-4)

Conditions	Yield
In isopropyl alcohol at 70℃; for 24h; Heating / reflux;

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + C16H20N2O → C34H35N3O4 (1055276-56-6)

Conditions	Yield
In isopropyl alcohol at 70℃; for 36h; Heating / reflux;
In isopropyl alcohol

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) + C28H28N2O → C46H43N3O4 (1055276-52-2)

Conditions	Yield
In isopropyl alcohol at 70℃; for 34h; Heating / reflux;
In isopropyl alcohol at 78℃; for 16h;

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) → 8-benzyloxy-5-[R-1-hydroxy-2-(2,3,4,7-tetrahydro-1H-inden-2-ylamino)ethyl]-1H-quinolin-2-one (774222-36-5)

Conditions	Yield
Stage #1: 2,3,4,7-tetrahydro-1H-inden-2-ylamine With N,O-bis-(trimethylsilyl)-acetamide In DMF (N,N-dimethyl-formamide) at 20℃; for 0.5h; Stage #2: (R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone In DMF (N,N-dimethyl-formamide) at 80℃; for 96h; Heating / reflux;

(R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone (173140-90-4) → 8-benzyloxy-5-[R-2-(S-5-(furan-2-yl)-indan-2-ylamino)-1-hydroxyethyl]-1H-quinolin-2-one (774222-67-2)

Conditions	Yield
Stage #1: S-5-(furan-2-yl)indan-2-ylamine With N,O-bis-(trimethylsilyl)-acetamide In DMF (N,N-dimethyl-formamide) for 0.5h; Stage #2: (R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone In DMF (N,N-dimethyl-formamide) at 85℃; for 48h; Heating / reflux;

Upstream product

• 530084-79-8 8-(benzyloxy)-5-[(1R)-2-bromo-1-hydroxyethyl]quinolin-2(1H)-one 
• 100331-89-3 8-benzyloxy-5-(2-bromoacetyl)-1H-quinolin-2-one 
• 148-24-3 8-quinolinol 
• 2598-31-4 5-acetyl-8-hydroxyquinoline 
• 26872-48-0 1-(8-benzyloxyquinolin-5-yl)ethanone 
• 100331-93-9 5-Acetyl-8-benzyloxyquinoline-N-oxide 
• 57434-96-5 5-acetyl-8-hydroxyquinoline hydrochloride 
• 100-39-0 benzyl bromide 
• 93609-84-8 5-acetyl-8-benzyloxy-1H-quinolin-2-one 

Downstream Products

• 662111-65-1 8-benzyloxy-5-[(R)-2-benzylamino-1-hydroxyethyl]-(1H)-quinolin-2-one 
• 1064594-84-8 C₄₄H₄₁N₅O₅S 
• 1064594-80-4 C₄₃H₄₄N₄O₆S 
• 1055276-56-6 C₃₄H₃₅N₃O₄ 
• 1055276-52-2 C₄₆H₄₃N₃O₄ 
• 774222-36-5 8-benzyloxy-5-[R-1-hydroxy-2-(2,3,4,7-tetrahydro-1H-inden-2-ylamino)ethyl]-1H-quinolin-2-one 
• 774222-67-2 8-benzyloxy-5-[R-2-(S-5-(furan-2-yl)-indan-2-ylamino)-1-hydroxyethyl]-1H-quinolin-2-one 
• 774222-28-5 8-benzyloxy-5-[R-1-hydroxy-2-(R-indan-1-ylamino)ethyl]-1H-quinolin-2-one 
• 774222-30-9 8-benzyloxy-5-{R-1-hydroxy-2-[R-(1,2,3,4-tetrahydronaphthalen-1-yl)amino]-ethyl}-1H-quinolin-2-one 
• 774222-45-6 8-benzyloxy-5-[R-1-hydroxy-2-(2-methoxymethylindan-2-ylamino)-ethyl]-1H-quinolin-2-one 
• 774222-47-8 5-[R-2-(2-benzylindan-2-ylamino)-1-hydroxyethyl]-8-benzyloxy-1H-quinolin-2-one 
• 774222-52-5 (3aS,5S,6aR)-5-[R-2-(8-benzyloxy-2-oxo-1,2-dihydro-quinolin-5-yl)-2-hydroxy-ethylamino]-2-cyclohexylmethyl-tetrahydrocyclopenta[c]pyrrole-1,3-dione 
• 774603-81-5 5-[R-2-(4b,10-dihydro-9H-indeno-[1,2-a]inden-9a-ylamino)-1-hydroxyethyl]-8-benzyloxy-1H-quinolin-2-one 
• 774222-22-9 8-benzyloxy-5-(R-2-{[(2,4-dimethoxyphenyl)-(2-methoxyphenyl)methyl]amino}-1-hydroxyethyl)-1H-quinolin-2-one 

Relevant academic research and scientific papers

PROCESS FOR PREPARING ISOMERS OF CARMOTEROL

A process for preparing a compound of formula (III) comprising condensing an oxiranyl compound of formula (I) with an amine of formula (II) or a salt thereof wherein: R1 is a group selected from alkyl, aryl, allyl, alkoxy, cycloalkyl, heterocyclic, alkenyl, benzocycloalkyl, aralkyl, haloarylalkyl, heteroaralkyl, haloalkyl, alkoxyaralkyl, substituted silyl and benzyl; and R2 is hydrogen, optionally substituted silyl or optionally substituted benzyl. Formula (I), (II) and (III): There is also described a process for preparing (R,R)-carmoterol from compound (III).

ORGANIC COMPOUNDS

A process for preparing 8-substituted oxy-5-((R)-2-halo-l-hydroxy-ethyl)-(1 H)-quinolin-2-ones or acceptable solvates thereof. The process involves reacting a 5-(α-haloacetyl)-8-substituted oxy-(1H)-quinolin-2-one with a reducing agent in the presence of a chiral agent and a base to form a 8-(substituted oxy)-5-((R)-2-halo-l-hydroxy-ethyl)-(1H)-quinolin-2-one, said chiral agent having a formula (I) or (II), wherein M, L, X, R1, R2 and R3 have the meanings as indicated in the specification.

A PROCESS FOR THE PREPARATION OF 5-(HALOACETYL)-8-(SUBSTITUTED OXY)-(1H)-QUINOLIN-2-ONES

The invention relates to a process for preparing 5-(α-haloacetyl)-8-substituted oxy-(1H)-quinolin-2-ones. The process involves (i) reacting (a) 8-hydroxy-(1H)-quinolin-2-one with an acylating agent and a Lewis acid to form 5-acetyl-8-hydroxy-(1H)-quinolin-2-one; or (b) 8-hydroxy-(lH)-quinolin-2-one with an acylating agent to form 8-acetoxy-(lH)-quinolin-2-one, and treating, in-situ, the 8-acetoxy-(1H)-quinolin-2-one with a Lewis acid to form 5-acetyl-8-hydroxy-(1H)-quinolin-2-one; or (c) 8-acetoxy-(1H)-quinolin-2-one with a Lewis acid to form 5-acetyl-8-hydroxy-(lH)-quinolin-2-one; (ii) reacting the 5-acetyl-8-hydroxy-(1H)-quinolin-2-one prepared in Step (i) with a compound having the Formula RL in the presence of a base and a solvent to form 5-acetyl-8-substituted oxy-(1H)-quinolin-2-one, wherein R is a protecting group and L is a leaving group; and (iii) reacting the 5-acetyl-8-substituted oxy-(1H)-quinolin-2-one with a halogenating agent in the presence of a solvent to form a 5-(α-haloacetyl)-8-substituted oxy-(1H)-quinolin-2-one.

PROCESS FOR PREPARING 5-'(R)-2-(5,6-DIETHYL-INDIAN-2-YLAMINO)-1-HYDROXY-ETHYL!-8-HYDROXY-(1H)-QUINOLIN-2-ONE SALT, USEFUL AS AN ADRENOCEPTOR AGONIST

A process for preparing 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-(1H)-quinolin-2-one salt. The process involves forming an acid salt of 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-substituted oxy-(1 H)-quinolin-2-one (V); and converting the acid salt to a salt of 5-[(R)-2-(5, 6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-(1H)-quinolin-2-one (VI) without isolating the free base of 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-(1H)-quinolin-2-one. Formula (A); (V): R = a protecting group, (VI): R = H.