35364-15-9

Basic information

• Product Name: 1-(2-Amino-5-hydroxyphenyl)propan-1-one
• Synonyms: 1-(2-Amino-5-hydroxyphenyl)propan-1-one;1-propanone,1-(2-amino-5-hydroxyhenyl)-;2-Amino-5-Hydroxy propiophenone
• CAS NO: 35364-15-9
• Molecular Formula: C₉H₁₁NO₂
• Molecular Weight: 165.19
• Mol File: 35364-15-9.mol
• Article Data: 6

Chemical Properties

• Melting Point: 144.5-144.9 °C
• Boiling Point: 363.9±32.0 °C(Predicted)
• Appearance: /
• Density: 1.195±0.06 g/cm3(Predicted)
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility: Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
• PKA: 9.35±0.18(Predicted)
• Stability: Hygroscopic
• CAS DataBase Reference: 1-(2-Amino-5-hydroxyphenyl)propan-1-one(CAS DataBase Reference)
• NIST Chemistry Reference: 1-(2-Amino-5-hydroxyphenyl)propan-1-one(35364-15-9)
• EPA Substance Registry System: 1-(2-Amino-5-hydroxyphenyl)propan-1-one(35364-15-9)

Safety Data

• Hazardous Substances Data: 35364-15-9(Hazardous Substances Data)

Usage

Uses

1-(2-Amino-5-hydroxyphenyl)propan-1-one is a useful synthetic intermediate. It is used in the asymmetrical synthesis of (S)-4-ethyl-6,7,8,10- tetrahydro-4-hydroxy-1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione, a key intermediate for synthesis of irinotecan and other camptothecin analogs. It is also used in the synthesis of E-?ring-?modified (RS)?-?camptothecin analogs as antitumor agents.

Preparation

Obtained by UV-irradiation of 3-ethyl-2,1-benzisoxazole in 66% sulfuric acid for 90 min at 80–90° Also prepared from 2-nitro-5-hydroxybenzaldehyde (five steps) or from p-anisidine.

Synthetic route

1-(5-hydroxy-2-nitrophenyl)propan-1-one (453518-19-9) → 2'-amino-5'-hydroxypropiophenone (35364-15-9)

Conditions	Yield
With sodium dithionite; water; sodium carbonate at 20℃; for 1h;	92%
With methanol; sodium dithionite; water; sodium carbonate at 0 - 20℃; for 3h;
With sodium dithionite; water; sodium carbonate In methanol at 0 - 20℃; for 3h;
With sodium dithionite; sodium carbonate In methanol at 0 - 30℃; for 1h;	3.6 g

1-(5-benzyloxy-2-nitrophenol)-2-propen-1-one (453518-18-8) → 2'-amino-5'-hydroxypropiophenone (35364-15-9)

Conditions	Yield
With hydrogen; palladium 10% on activated carbon In ethyl acetate at 0 - 25℃; for 13h;	84%

1-(5-benzyloxy-2-nitrophenol)-2-propen-1-one (453518-18-8) → 2'-amino-5'-hydroxypropiophenone (35364-15-9) + 1-(5-hydroxy-2-nitrophenyl)propan-1-one (453518-19-9)

Conditions	Yield
With hydrogen; palladium 10% on activated carbon In ethyl acetate at 0 - 25℃;	A 14% B 0%

ethyl bromide (74-96-4) + 2-amino-5-methoxybenzonitrile (23842-82-2) → 2'-amino-5'-hydroxypropiophenone (35364-15-9)

Conditions	Yield
Stage #1: ethyl bromide With magnesium In tetrahydrofuran for 0.833333h; Inert atmosphere; Reflux; Stage #2: 2-amino-5-methoxybenzonitrile In tetrahydrofuran at 5 - 20℃; Further stages;	3.5 g

1-(5-fluoro-2-nitrophenyl)propan-1-one (924648-17-9) → 2'-amino-5'-hydroxypropiophenone (35364-15-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydroxide / 2 h / 0 - 20 °C 2: lithium chloride / N,N-dimethyl-formamide / 6 h / Reflux 3: sodium carbonate; sodium dithionite; water / 1 h / 20 °C View Scheme

1-(5-methoxy-2-nitrophenyl)propan-1-one → 2'-amino-5'-hydroxypropiophenone (35364-15-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium chloride / N,N-dimethyl-formamide / 6 h / Reflux 2: sodium carbonate; sodium dithionite; water / 1 h / 20 °C View Scheme

3-Fluorobenzaldehyde (456-48-4) → 2'-amino-5'-hydroxypropiophenone (35364-15-9)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: hydroxylamine hydrochloride; sodium hydroxide; water / ethanol / 4 h / 5 °C 2.1: acetic anhydride / 2 h / 110 °C 3.1: magnesium / tetrahydrofuran / 0.5 h / 40 °C 3.2: 1 h / 40 °C 4.1: nitric acid / dichloromethane / 12 h / 10 - 20 °C 5.1: sodium hydroxide / 2 h / 0 - 20 °C 6.1: lithium chloride / N,N-dimethyl-formamide / 6 h / Reflux 7.1: sodium carbonate; sodium dithionite; water / 1 h / 20 °C View Scheme

3-fluorobenzaldehyde oxime (458-02-6) → 2'-amino-5'-hydroxypropiophenone (35364-15-9)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: acetic anhydride / 2 h / 110 °C 2.1: magnesium / tetrahydrofuran / 0.5 h / 40 °C 2.2: 1 h / 40 °C 3.1: nitric acid / dichloromethane / 12 h / 10 - 20 °C 4.1: sodium hydroxide / 2 h / 0 - 20 °C 5.1: lithium chloride / N,N-dimethyl-formamide / 6 h / Reflux 6.1: sodium carbonate; sodium dithionite; water / 1 h / 20 °C View Scheme

m-Fluorobenzonitrile (403-54-3) → 2'-amino-5'-hydroxypropiophenone (35364-15-9)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: magnesium / tetrahydrofuran / 0.5 h / 40 °C 1.2: 1 h / 40 °C 2.1: nitric acid / dichloromethane / 12 h / 10 - 20 °C 3.1: sodium hydroxide / 2 h / 0 - 20 °C 4.1: lithium chloride / N,N-dimethyl-formamide / 6 h / Reflux 5.1: sodium carbonate; sodium dithionite; water / 1 h / 20 °C View Scheme

1-(3-fluorophenyl)propan-1-one (455-67-4) → 2'-amino-5'-hydroxypropiophenone (35364-15-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: nitric acid / dichloromethane / 12 h / 10 - 20 °C 2: sodium hydroxide / 2 h / 0 - 20 °C 3: lithium chloride / N,N-dimethyl-formamide / 6 h / Reflux 4: sodium carbonate; sodium dithionite; water / 1 h / 20 °C View Scheme

C16H22O4 → 2'-amino-5'-hydroxypropiophenone (35364-15-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium sulfate; potassium nitrate; sulfuric acid / dichloromethane / 5 - 30 °C / Inert atmosphere 2.1: potassium carbonate / methanol / 1 h / 25 - 30 °C 2.2: pH 1.5 3.1: sodium dithionite; sodium carbonate / methanol / 1 h / 0 - 30 °C View Scheme

C12H11Cl3O4 → 2'-amino-5'-hydroxypropiophenone (35364-15-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium sulfate; potassium nitrate; sulfuric acid / dichloromethane / -1 - 30 °C 2.1: potassium carbonate / methanol / 1 h / 25 - 30 °C 2.2: 1 h / 5 - 30 °C View Scheme
Multi-step reaction with 3 steps 1.1: sodium sulfate; potassium nitrate; sulfuric acid / dichloromethane / -1 - 30 °C 2.1: potassium carbonate / methanol / 1 h / 25 - 30 °C 2.2: pH 3.5 3.1: sodium dithionite; sodium carbonate / methanol / 1 h / 0 - 30 °C View Scheme

C12H10Cl3NO6 → 2'-amino-5'-hydroxypropiophenone (35364-15-9)

Conditions	Yield
Stage #1: C12H10Cl3NO6 With potassium carbonate In methanol at 25 - 30℃; for 1h; Stage #2: With sodium dithionite; sodium carbonate In methanol; water at 5 - 30℃; for 1h;	57.6 g
Multi-step reaction with 2 steps 1.1: potassium carbonate / methanol / 1 h / 25 - 30 °C 1.2: pH 3.5 2.1: sodium dithionite; sodium carbonate / methanol / 1 h / 0 - 30 °C View Scheme

1-(3-hydroxyphenyl)propan-1-one (13103-80-5) → 2'-amino-5'-hydroxypropiophenone (35364-15-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: nitric acid; acetic acid / water; ethyl acetate 2: sodium dithionite; sodium carbonate / methanol / 1 h / 0 - 30 °C View Scheme
Multi-step reaction with 3 steps 1.1: sodium hydroxide / water / 0.17 h / 0 - 30 °C 1.2: 2 h / 0 - 10 °C 2.1: sodium sulfate; potassium nitrate; sulfuric acid / dichloromethane / -1 - 30 °C 3.1: potassium carbonate / methanol / 1 h / 25 - 30 °C 3.2: 1 h / 5 - 30 °C View Scheme
Multi-step reaction with 4 steps 1.1: sodium hydroxide / water / 0.17 h / 0 - 30 °C 1.2: 2 h / 0 - 10 °C 2.1: sodium sulfate; potassium nitrate; sulfuric acid / dichloromethane / -1 - 30 °C 3.1: potassium carbonate / methanol / 1 h / 25 - 30 °C 3.2: pH 3.5 4.1: sodium dithionite; sodium carbonate / methanol / 1 h / 0 - 30 °C View Scheme
Multi-step reaction with 4 steps 1.1: sodium hydroxide / water; dichloromethane / 0.17 h / 0 - 10 °C 1.2: 0 - 10 °C 2.1: sodium sulfate; potassium nitrate; sulfuric acid / dichloromethane / 5 - 30 °C / Inert atmosphere 3.1: potassium carbonate / methanol / 1 h / 25 - 30 °C 3.2: pH 1.5 4.1: sodium dithionite; sodium carbonate / methanol / 1 h / 0 - 30 °C View Scheme
Multi-step reaction with 4 steps 1.1: sodium hydroxide / water; dichloromethane / 0.17 h / 0 - 10 °C 1.2: 10 °C 2.1: sodium sulfate; potassium nitrate; sulfuric acid / dichloromethane / 0 - 30 °C / Inert atmosphere 3.1: potassium carbonate / methanol / 1 h / 25 - 30 °C 3.2: pH 1.2 4.1: sodium dithionite; sodium carbonate / methanol / 1 h / 0 - 30 °C View Scheme

C16H21NO6 → 2'-amino-5'-hydroxypropiophenone (35364-15-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium carbonate / methanol / 1 h / 25 - 30 °C 1.2: pH 1.5 2.1: sodium dithionite; sodium carbonate / methanol / 1 h / 0 - 30 °C View Scheme

C12H14O4 → 2'-amino-5'-hydroxypropiophenone (35364-15-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium sulfate; potassium nitrate; sulfuric acid / dichloromethane / 0 - 30 °C / Inert atmosphere 2.1: potassium carbonate / methanol / 1 h / 25 - 30 °C 2.2: pH 1.2 3.1: sodium dithionite; sodium carbonate / methanol / 1 h / 0 - 30 °C View Scheme

2'-amino-5'-hydroxypropiophenone (35364-15-9) + (4S)-4-ethyl-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione (110351-94-5) → 7-ethyl-10-hydroxycamptothecin (86639-52-3, 110714-48-2, 130144-34-2)

Conditions	Yield
With trifluoroacetic acid In toluene at 80℃; for 6h;	92%
With toluene-4-sulfonic acid; acetic acid In toluene at 103℃; for 5.25 - 5.33h; Product distribution / selectivity;	90.5%
Stage #1: 2'-amino-5'-hydroxypropiophenone; (4S)-4-ethyl-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione With toluene-4-sulfonic acid In acetic acid; toluene at 20℃; Stage #2: at 100℃; for 18h;	89%

2'-amino-5'-hydroxypropiophenone (35364-15-9) + 4-Ethyl-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione (102978-40-5) → 7-ethyl-10-hydroxycamptothecin (86639-52-3, 110714-48-2, 130144-34-2)

Conditions	Yield
With iodine In N,N-dimethyl-formamide at 80℃; for 8h; Friedlaender synthesis; Inert atmosphere;	75%

2'-amino-5'-hydroxypropiophenone (35364-15-9) + 2-tert-butoxycarbonyloxyimino-2-phenylacetonitrile → 2'-amino-5'-tert-butoxycarbonyloxypropiophenone (141975-09-9)

Conditions	Yield
With triethylamine In 1,4-dioxane; water for 24h; Ambient temperature;	55.9%

2'-amino-5'-hydroxypropiophenone (35364-15-9) + acetic anhydride (108-24-7) → 2-acetamido-5-hydroxy-propiophenone

Conditions	Yield
at 130℃; for 2 - 3h;

2'-amino-5'-hydroxypropiophenone (35364-15-9) + propionic acid anhydride (123-62-6) → 2-propionamido-5-hydroxy-propiophenone

Conditions	Yield
at 130℃; for 2 - 3h;

2'-amino-5'-hydroxypropiophenone (35364-15-9) + Chloroacetic anhydride (541-88-8) → 2-chloroacetamido-5-hydroxy-propiophenone

Conditions	Yield
at 130℃; for 2 - 3h;

2'-amino-5'-hydroxypropiophenone (35364-15-9) → 20-deethylallyl-7-ethyl-10-hydroxycamptothecin (141975-10-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 55.9 percent / Et3N / dioxane; H2O / 24 h / Ambient temperature 2: 1.) AcOH, 2.) p-TsOH*H2O / 1.) 60 deg C, 0.5 h, 2.) 60 deg C, 15 h View Scheme

1-chloroformyl-4-piperidinylpiperidine monohydrochloride + 2'-amino-5'-hydroxypropiophenone (35364-15-9) → 4-amino-3-propionylphenyl-1,4'-bipiperidine-1'-carboxylate

Conditions	Yield
With pyridine at 20℃; for 13h;
With pyridine at 20℃; for 13h;

6,6-(ethylenedioxy)-4-(2-fluoroethyl)-1,4,7,8-tetrahydro-4-hydroxypyrano[3,4-f]indolizine-3,10 (6H)-dione (142606-95-9) + chloroform methanol (7285-11-2) + 2'-amino-5'-hydroxypropiophenone (35364-15-9) → 11-ethyl-4-(2-fluoroethyl)-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione

Conditions	Yield
With acetic acid In aqueous 80%-trifluoroacetic acid; dichloromethane

2'-amino-5'-hydroxypropiophenone (35364-15-9) → irinotecan hydrochloirde (100286-90-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: trifluoroacetic acid / toluene / 20 h / 85 - 90 °C / Industry scale 2: 1-Methylpyrrolidine / dichloromethane / 20 - 45 °C 3: hydrogenchloride / water / 3 h / 70 °C View Scheme
Multi-step reaction with 3 steps 1: trifluoroacetic acid / toluene / 6 h / 80 °C 2: triethylamine; pyridine / 2 h / 20 °C / Inert atmosphere 3: hydrogenchloride; water / 3 h / 20 - 70 °C View Scheme
Multi-step reaction with 4 steps 1.1: toluene-4-sulfonic acid / toluene / 5 h / Reflux 2.1: lithium hydroxide / methanol; water / 1 h / 25 - 30 °C 2.2: 18 - 22 °C 3.1: sulfuric acid / 2 h / 0 - 5 °C 4.1: triethylamine; pyridine / dichloromethane / 20 - 40 °C 4.2: pH 2-3 View Scheme

2'-amino-5'-hydroxypropiophenone (35364-15-9) → irinotecan (97682-44-5, 130144-33-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: trifluoroacetic acid / toluene / 20 h / 85 - 90 °C / Industry scale 2: 1-Methylpyrrolidine / dichloromethane / 20 - 45 °C View Scheme
Multi-step reaction with 2 steps 1: trifluoroacetic acid / toluene / 6 h / 80 °C 2: triethylamine; pyridine / 2 h / 20 °C / Inert atmosphere View Scheme

2'-amino-5'-hydroxypropiophenone (35364-15-9) + 4-Ethyl-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione (102978-40-5) → 4,11-diethyl-4,9-dihydroxy-1H-pyrano[3′,4′:6,7]indolizino[1,2-b]quinoline-3,14 (4H,12H)-dione (130144-34-2)

Conditions	Yield
With toluene-4-sulfonic acid In toluene for 5h; Time; Reflux;	422 g

2'-amino-5'-hydroxypropiophenone (35364-15-9) → 7-ethyl-10-hydroxycamptothecin (86639-52-3, 110714-48-2, 130144-34-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / toluene / 5 h / Reflux 2.1: lithium hydroxide / methanol; water / 1 h / 25 - 30 °C 2.2: 18 - 22 °C 3.1: sulfuric acid / 2 h / 0 - 5 °C View Scheme

2'-amino-5'-hydroxypropiophenone (35364-15-9) → C22H22N2O6*C9H13NO

Conditions	Yield
Multi-step reaction with 2 steps 1.1: toluene-4-sulfonic acid / toluene / 5 h / Reflux 2.1: lithium hydroxide / methanol; water / 1 h / 25 - 30 °C 2.2: 18 - 22 °C View Scheme

Upstream product

• 13103-80-5 1-(3-hydroxyphenyl)propan-1-one 
• 455-67-4 1-(3-fluorophenyl)propan-1-one 
• 403-54-3 m-Fluorobenzonitrile 
• 458-02-6 3-fluorobenzaldehyde oxime 
• 456-48-4 3-Fluorobenzaldehyde 
• 924648-17-9 1-(5-fluoro-2-nitrophenyl)propan-1-one 
• 74-96-4 ethyl bromide 
• 23842-82-2 2-amino-5-methoxybenzonitrile 
• 453518-19-9 1-(5-hydroxy-2-nitrophenyl)propan-1-one 
• 453518-18-8 1-(5-benzyloxy-2-nitrophenol)-2-propen-1-one 

Downstream Products

• 86639-52-3 7-ethyl-10-hydroxycamptothecin 
• 130144-34-2 4,11-diethyl-4,9-dihydroxy-1H-pyrano[3′,4′:6,7]indolizino[1,2-b]quinoline-3,14 (4H,12H)-dione 
• 97682-44-5 irinotecan 
• 100286-90-6 irinotecan hydrochloirde 
• 141975-09-9 2'-amino-5'-tert-butoxycarbonyloxypropiophenone 

Relevant articles and documents

PROCESS FOR PREPARATION OF 2-AMINO-5-HYDROXY PROPIOPHENONE

The present invention relates to a process for preparation of 2-Amino-5-hydroxypropiophenone, a key intermediate for the synthesis of camptothecin analogs including 7-Ethyl-10-hydroxycamptothecin (SN-38).

A novel and practical synthesis of 2-amino-5-hydroxypropiophenone

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METHOD OF SYNTHESIZING KEY INTERMEDIATES FOR THE PRODUCTION OF CAMPTOTHECIN DERIVATIVES

The present invention discloses a process for efficient production of 2-amino-5- hydroxypropiophenone corresponding to the AB ring part of camptothecin (CPT) skelton, which is a key intermediate useful for the total synthesis of camptothecin analogs including 7-Ethyl-10-hydroxy camptothecin and novel intermediates thereof.