279262-23-6

Basic information

• Product Name: 4-(Morpholinomethyl)phenylboronic acid
• Synonyms: B-[4-(4-morpholinylmethyl)phenyl]Boronic acid;4-(Morpholinylmethyl)phenylboronic acid;4-(Morpholinomethyl)phenylboronic acid;3)4-(MORPHOLINOMETHYL)PHENYLBORONIC ACID;Boronic acid, B-[4-(4-morpholinylmethyl)phenyl]-;[4-(morpholin-4-ylmethyl)phenyl]boronic acid;4-(Morpholinomethyl)phenylboronic Acid (contains varying amounts of Anhydride)
• CAS NO: 279262-23-6
• Molecular Formula: C₁₁H₁₆BNO₃
• Molecular Weight: 221.062
• Product Categories: Boronate Ester;Boronic Acid;Potassium Trifluoroborate
• Mol File: 279262-23-6.mol
• Article Data: 10

Chemical Properties

• Melting Point: 85 °C
• Boiling Point: 382.268 °C at 760 mmHg
• Flash Point: 184.989 °C
• Appearance: /
• Density: 1.20
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• CAS DataBase Reference: 4-(Morpholinomethyl)phenylboronic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 4-(Morpholinomethyl)phenylboronic acid(279262-23-6)
• EPA Substance Registry System: 4-(Morpholinomethyl)phenylboronic acid(279262-23-6)

Safety Data

• Hazardous Substances Data: 279262-23-6(Hazardous Substances Data)

Usage

General Description

4-(Morpholinomethyl)phenylboronic acid is an organic chemical compound that is often used in chemical research studies. This substance is known for its role as a reactive intermediate, often used in the preparation of more complex organic compounds. The chemical contains boronic acid, which is a type of compound that often reacts with compounds bearing a diol to form a cyclic boronate ester. It also contains a morpholine ring, a common feature in various pharmaceutical drugs due to its polarity and basicity. The chemical is typically a solid at room temperature and must be handled with care as it may cause skin and eye irritation, or chronic effects if improperly handled or inhaled.

Synthetic route

morpholine (110-91-8) + 4-bromomethylphenylboronic acid (68162-47-0) → 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6)

Conditions	Yield
Stage #1: 4-bromomethylphenylboronic acid With N,N-diethanolaminomethyl polystyrene In dichloromethane at 20℃; for 1.66667h; Stage #2: morpholine In 1-methyl-pyrrolidin-2-one at 20℃; for 5h; Stage #3: In tetrahydrofuran; water at 20℃; Further stages.;	88%
In tetrahydrofuran for 2h; Heating / reflux;
With potassium carbonate In acetonitrile at 10 - 35℃; for 60h;	449 mg

C11H14BF3NO(1-)*K(1+) → 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6)

Conditions	Yield
With water; silica gel In ethyl acetate at 20℃; for 3h;	87%

(OC4H8NCH2C6H4)BN(CH3)(CH2CO2)2 (1072960-75-8) → 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6)

Conditions	Yield
With sodium hydroxide; water In tetrahydrofuran at 23℃; for 0.166667h; Inert atmosphere;	76%

(2R)-4-(6-bromo-1-oxoisoquinolin2(1H)-yl)-2-methyl-2-(methylsulfonyl)-N-((tetrahydro-2H-pyran-2-yl)oxy)butanamide + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → (2R)-2-methyl-2-(methylsulfonyl)-4-(6-(4-(morpholinomethyl)phenyl)-1-oxoisoquinolin-2(1H)-yl)-N-((tetrahydro-2H-pyran-2-yl)oxy)butanamide

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In 1,4-dioxane; water at 120℃; for 0.5h; Sealed tube; Microwave irradiation;	96%

C25H30BrN3O4 + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → 6-(4-morpholin-4-ylmethylphenyl)-4-(tetrahydropyran-4-yl)-3,4-dihydro-2H-benzo[1,4]oxazine-8-carboxylic acid (1-methyl-3-oxo-2,3,5,6,7,8-hexahydroisoquinolin-4-ylmethyl)amide

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate In 1,4-dioxane; water at 100℃; for 3h; Suzuki Coupling; Inert atmosphere;	89%

6-bromo-3-iodo-2-(naphthalen-1-ylmethoxy)quinoline + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → 6-bromo-3-(4-(morpholinomethyl)phenyl)-2-(naphthalen-1-ylmethoxy)quinoline

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In water; toluene at 80℃; Suzuki-Miyaura Coupling;	86.8%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In water; toluene at 80℃; for 10h;	76.15%

(R)-ethyl 4-(7-bromo-4-oxoquinazolin-3(4H)-yl)-2-methyl-2-(methylsulfonyl)butanoate + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → (R)-ethyl 2-methyl-2-(methylsulfonyl)-4-(7-(4-(morpholinomethyl)phenyl)-4-oxoquinazolin-3(4H)-yl)butanoate

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate at 110℃; for 0.5h; Microwave irradiation;	86%

5-bromo-3-(ethyl (tetrahydro-2H-pyran-4-yl)amino)-2-methyl-N-((1-methyl-3-oxo-2,3,5,6,7,8-hexahydroisoquinolin-4-yl)methyl)benzamide + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → 5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-N-((1-methyl-3-oxo-2,3,5,6,7,8-hexahydroisoquinolin-4-yl)methyl)-4'-(morpholinomethyl)-[1,1'-biphenyl]-3-carboxamide

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate In 1,4-dioxane; water at 100℃; for 4h; Suzuki Coupling; Inert atmosphere;	85%

4-bromo-2-iodo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine (889939-26-8) + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → 4-bromo-2-[4-(N-morpholinylmethyl)phenyl]-1-phenylsulfonyl-1H-pyrrolo[2,3-b]pyridine (942920-82-3)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate In water; N,N-dimethyl-formamide at 100℃; for 16h; Suzuki coupling; Inert atmosphere;	84%

(R)-ethyl 4-(7-bromo-8-methyl-4-oxoquinazolin-3(4H)-yl)-2-methyl-2-(methylsulfonyl)butanoate + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → (R)-ethyl 2-methyl-4-(8-methyl-7-(4-(morpholinomethyl)phenyl)-4-oxoquinazolin-3(4H)-yl)-2-(methylsulfonyl)butanoate

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In 1,4-dioxane; water at 110℃; for 0.5h; Inert atmosphere;	82%

(R)-3-bromo-6-((4-hydroxy-1-(4,4,4-trifluoro-3-phenylbutanoyl)piperidin-4-yl)methyl)-2-methyl-2H-pyrazolo[4,3-d]pyrimidin-7(6H)-one + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → (R)-6-((4-hydroxy-1-(4,4,4-trifluoro-3-phenylbutanoyl)piperidin-4-yl)methyl)-2-methyl-3-(4-(morpholinomethyl)phenyl)-2H-pyrazolo[4,3-d]pyrimidin-7(6H)-one

Conditions	Yield
With potassium phosphate; tetrakis(triphenylphosphine) palladium(0) In 1,4-dioxane; water at 130℃; for 0.5h; Suzuki Coupling; Inert atmosphere; Sealed tube; Microwave irradiation;	82%

6-Bromo-1H-pyrrolo<2,3-b>pyridine (143468-13-7) + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → 4-[[4-(1H-pyrrolo[2,3-b]pyridin-6-yl)phenyl]methyl]morpholine (1542067-50-4)

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium hydrogencarbonate In 1,2-dimethoxyethane; water at 110℃; for 1h; Suzuki-Miyaura Coupling; Inert atmosphere;	81%

C17H24BrO4P + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → (Z)-2-(1-phenyl-1-(4-(1-morpholinomethyl)phenyl)hexen-2-yloxy)-5,5-dimethyldioxaphosphorane

Conditions	Yield
With potassium phosphate; palladium diacetate; ruphos In water; toluene at 50℃; for 20h; Suzuki Coupling; Inert atmosphere;	81%

5-bromo-2-chloropyridine (53939-30-3) + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → 4-(4-(6-chloropyridin-3-yl)benzyl)morpholine

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In 1,4-dioxane; water at 80℃; for 4h; Inert atmosphere;	80.22%

C22H26BrN3O3 + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → 4-cyclopentyl-6-(4-morpholin-4-ylmethylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazine-8-carboxylic acid (4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-ylmethyl)amide

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate In 1,4-dioxane; water at 100℃; for 3h; Suzuki Coupling; Inert atmosphere;	79%

2-chloro-quinoline-4-carboxylic acid-(2-diethylamino-ethylamide) (87864-14-0) + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → N-[2-(diethylamino)ethyl]-2-{4-[(morpholin-4-yl)methyl]phenyl}quinoline-4-carboxamide

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 140℃; for 0.5h; Suzuki-Miyaura Coupling; Inert atmosphere; Microwave irradiation;	77%

C23H28BrN3O4 + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → C34H42N4O5

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate In 1,4-dioxane; water at 100℃; for 3h; Suzuki Coupling; Inert atmosphere;	77%

C24H24BrN3O3 + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → 4-benzyl-6-(4-morpholin-4-ylmethylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazine-8-carboxylic acid (4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-ylmethyl)amide

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate In 1,4-dioxane; water at 100℃; for 3h; Suzuki Coupling; Inert atmosphere;	76%

ethyl 4-iodo-5-(5-isopropyl-2,4-dimethoxyphenyl)isoxazole-3-carboxylate + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → ethyl 5-(5-isopropyl-2,4-dimethoxyphenyl)-4-(4-(morpholinomethyl)phenyl)isoxazole-3-carboxylate

Conditions	Yield
Stage #1: ethyl 4-iodo-5-(5-isopropyl-2,4-dimethoxyphenyl)isoxazole-3-carboxylate; [4-(morpholin-4-ylmethyl)phenyl]boronic acid With sodium hydrogencarbonate In water; N,N-dimethyl-formamide for 0.166667h; Suzuki Coupling; Inert atmosphere; Stage #2: With bis-triphenylphosphine-palladium(II) chloride In water; N,N-dimethyl-formamide at 90℃; for 8h; Suzuki Coupling; Inert atmosphere;	76%

C27H28BrN3O3 + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → 4-benzyl-6-(4-morpholin-4-ylmethylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazine-8-carboxylic acid (1-methyl-3-oxo-2,3,5,6,7,8-hexahydroisoquinolin-4-ylmethyl)amide

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate In 1,4-dioxane; water at 100℃; for 3h; Suzuki Coupling; Inert atmosphere;	75%

C26H32BrN3O4 + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → C37H46N4O5

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate In 1,4-dioxane; water at 100℃; for 3h; Suzuki Coupling; Inert atmosphere;	74%

7-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,2-dimethyl-2,3-dihydrobenzofuran-5-carboxamide + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,2-dimethyl-7-(4-(morpholinomethyl)phenyl)-2,3-dihydrobenzofuran-5-carboxamide

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In N,N-dimethyl-formamide at 100℃; for 3h; Inert atmosphere; Sealed tube;	73%

C16H22F2NO(1+)*CF3O3S(1-) + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → C21H23F2NO2

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); copper(I) bromide dimethylsulfide complex; caesium carbonate; tris(para-trifluoromethyl)phenyl phosphine In 1,4-dioxane at 80℃; Molecular sieve; regioselective reaction;	72%

C25H30BrN3O3 + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → 4-cyclopentyl-6-(4-morpholin-4-ylmethylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazine-8-carboxylic acid (1-methyl-3-oxo-2,3,5,6,7,8-hexahydroisoquinolin-4-ylmethyl)amide

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate In 1,4-dioxane; water at 100℃; for 3h; Suzuki Coupling; Inert atmosphere;	70%

tert-butyl ((1R,4R)-4-((5-bromo-3-(((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-2-methylphenyl)(ethyl)amino)cyclohexyl)carbamate (1403258-28-5) + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → tert-butyl ((1R,4R)-4-((5-(((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)-methyl)-carbamoyl)-4-methyl-4'-(morpholinomethyl)-[1,1'-biphenyl]-3-yl)-(ethyl)-amino)-cyclohexyl)-carbamate (1403258-30-9)

Conditions	Yield
With sodium carbonate; tetrakis(triphenylphosphine) palladium(0) In 1,4-dioxane; water at 90℃; for 3.5h; Suzuki Coupling; Inert atmosphere;	67.48%

C20H24BrN3O3 + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → 4-isopropyl-6-(4-morpholin-4-ylmethylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazine-8-carboxylic acid (4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-ylmethyl)amide

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate In 1,4-dioxane; water at 100℃; for 3h; Suzuki Coupling; Inert atmosphere;	66%

5-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-(ethyl-d5 (tetrahydro-2H-pyran-4-yl)amino)-2-methylbenzamide (1403258-61-6) + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl-d5(tetrahydro-2H-pyran-4-yl)amino)-4'-formyl-4-methyl-[1,1'-biphenyl]-3-carboxamide (1403256-15-4)

Conditions	Yield
With sodium carbonate; tetrakis(triphenylphosphine) palladium(0) In 1,4-dioxane; water at 100℃; for 4h; Suzuki Coupling; Inert atmosphere;	61%

methyl 2-(5-iodo-4-(5-isopropyl-2,4-dimethoxyphenyl)-1H-1,2,3-triazol-1-yl)acetate + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → methyl 2-(4-(2,4-dihydroxy-5-isopropylphenyl)-5-(4-(morpholinomethyl)phenyl)-1H-1,2,3-triazol-1-yl)acetate

Conditions

Yield

Stage #1: methyl 2-(5-iodo-4-(5-isopropyl-2,4-dimethoxyphenyl)-1H-1,2,3-triazol-1-yl)acetate; [4-(morpholin-4-ylmethyl)phenyl]boronic acid With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate In water; N,N-dimethyl-formamide at 100℃; for 0.5h; Suzuki Coupling; Inert atmosphere; Microwave irradiation; Stage #2: With boron tribromide In dichloromethane; water; N,N-dimethyl-formamide at 40℃; for 2h; Inert atmosphere;

60%

5-bromo-2-chloro-3-methylpyridine (29241-60-9) + 4-(4-morpholin-1-ylmethyl)phenylboronic acid (279262-23-6) → 4-(4-(6-chloro-5-methylpyridin-3-yl)benzyl)morpholine

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate In 1,4-dioxane; water at 80℃; for 4h; Inert atmosphere;	47.73%

Upstream product

• 1072960-75-8 (OC₄H₈NCH₂C₆H₄)BN(CH₃)(CH₂CO₂)2 
• 110-91-8 morpholine 
• 68162-47-0 4-bromomethylphenylboronic acid 

Downstream Products

• 1174429-22-1 5-morpholino-3-(4-(morpholinomethyl)phenyl)-7H-thieno[3,2-b]pyran-7-one 
• 942920-82-3 4-bromo-2-[4-(N-morpholinylmethyl)phenyl]-1-phenylsulfonyl-1H-pyrrolo[2,3-b]pyridine 

Relevant articles and documents

Novel anticancer compound and usage thereof

The invention provides a novel anticancer compound. The novel anticancer compound is a compound shown in chemical formula 1 in the description or pharmaceutically acceptable salt of the compound, andthe compound and the salt are active ingredients of a pharmaceutical composition for inhibiting the activity of hepatocyte growth factor receptor (c-Met) tyrosine kinase and pharmaceutical compositionfor preventing or curing excessive or abnormal proliferative diseases. The compound effectively inhibits the activity of the hepatocyte growth factor receptor tyrosine kinase, thereby being suitablefor treating the diseases with the characteristics of excessive or abnormal cell proliferation.

CHEMICAL COMPOUNDS AS INHIBITORS OF KINASE ACTIVITY

The invention is directed to certain novel compounds. Specifically, the invention is directed to compounds of formula (I): (I) and salts thereof. The compounds of the invention are inhibitors of kinase activity, in particular PI3- kinase activity.

Efficient hydrolysis of organotrifluoroborates via silica gel and water

(Chemical Equation Presented) A general, mild, and efficient method for the hydrolysis of organotrifluoroborates to unveil boronic acids using silica gel and H2O was developed. This method proved to be tolerant of a broad range of aryl-, heteroaryl-, alkenyl-, and alkyltrifluoroborates as well as structurally diverse aminomethylated organotrifluoroborates.As anticipated, electron-rich substrates provided the corresponding boronic acids more readily than electron-poor substrates, owing to the resonance-stabilized difluoroborane intermediate. The method developed was expanded further for the conversion of organotrifluoroborates to the corresponding boronate esters. 2009 American Chemical Society.