40258-78-4

Basic information

• Product Name: 1-Bromoethyl acetate
• Synonyms: 1-ACETOXY ETHYL BROMIDE;1-BROMOETHYLACETATE;1-Bromoethyl acetate ,90%;(RS)-1-Acetoxyethyl BroMide;1 - broMine ethyl acetate;1-Bromoethyl acetate[BEA]
• CAS NO: 40258-78-4
• Molecular Formula: C₄H₇BrO₂
• Molecular Weight: 167
• EINECS: 1308068-626-2
• Mol File: 40258-78-4.mol
• Article Data: 5

Chemical Properties

• Boiling Point: 141.555 °C at 760 mmHg
• Flash Point: 68.548 °C
• Appearance: /
• Density: 1.48
• Vapor Pressure: 5.824mmHg at 25°C
• Refractive Index: 1.451
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• CAS DataBase Reference: 1-Bromoethyl acetate(CAS DataBase Reference)
• NIST Chemistry Reference: 1-Bromoethyl acetate(40258-78-4)
• EPA Substance Registry System: 1-Bromoethyl acetate(40258-78-4)

Safety Data

• Safety Statements: 24/25
• Hazardous Substances Data: 40258-78-4(Hazardous Substances Data)

Usage

Chemical Properties

Pale Yellow Oil

Uses

1-Bromoethyl Acetate is a 1-haloalkyl ester that is used in the modification of of antibiotics. It?is an intermediate that can be usefully used in the preparation of the oral antibiotic Cefuroxime axetil.

Synthesis

1-bromoethyl acetate is prepared by reacting acetyl bromide and acetaldehyde using zinc chloride as a catalyst.?After cooling 30 ml of hydrogen bromide / acetic acid (1.2 equiv) to 0 ° C., 53.5 ml (1.0 equiv) of vinyl acetate was slowly added thereto, followed by stirring for 1 hour. It was extracted with dichloromethane, washed with distilled water at 0-5 ° C., dehydrated with anhydrous magnesium sulfate, and distilled under reduced pressure to obtain 81.4 g of 1-bromoethyl acetate.

InChI:InChI=1/C4H7BrO2/c1-3(5)7-4(2)6/h3H,1-2H3

Synthetic route

vinyl acetate (108-05-4) + acetic acid (64-19-7) → 1-bromoethyl acetate (40258-78-4)

Conditions	Yield
With hydrogen bromide In dichloromethane at 5 - 10℃; for 1.5h; Inert atmosphere;	90.7%

vinyl acetate (108-05-4) → 1-bromoethyl acetate (40258-78-4)

Conditions	Yield
With iron(III) oxide; tetrabromosilane In water at 12 - 20℃; for 0.5h; Temperature;	89%
With hydrogen bromide; toluene-4-sulfonic acid at 15 - 25℃; for 4h; Reagent/catalyst; Temperature;	85.7%
With hydrogen bromide at 35℃; for 1h;	84%

Acetyl bromide (506-96-7) + paracetaldehyde (123-63-7) → 1-bromoethyl acetate (40258-78-4)

Conditions	Yield
With zinc(II) chloride at -5 - 5℃; for 5h; Temperature;	80.06%

Acetyl bromide (506-96-7) + acetaldehyde (75-07-0) → 1-bromoethyl acetate (40258-78-4)

Conditions	Yield
at 130℃;

1-bromoethyl acetate (40258-78-4) + Cefuroxime (55268-75-2) → cefuroxime axetil (64544-07-6)

Conditions	Yield
With N,N-dimethyl-formamide; copper dichloride In ethyl acetate at 8 - 30℃; for 1.5h; Temperature; Concentration;	98.2%

6-chloro-2-[5-hydroxy-2-(2-methoxyethoxymethoxy)biphenyl-3-yl]-1-methansulfonyl-1H-indole-5-carbonitrile (277313-34-5) + 1-bromoethyl acetate (40258-78-4) → CRA-9076

Conditions	Yield
With potassium carbonate; sodium iodide In acetonitrile at 20℃; for 18h;	98%

1-bromoethyl acetate (40258-78-4) + phenstatin (203448-32-2) → C21H24O8

Conditions	Yield
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 20℃;	98%

1-bromoethyl acetate (40258-78-4) + (S)-ibuprofen (51146-56-6) → (S)-(+)-ibuprofen-1-acetoxy ethyl ester (1418602-99-9)

Conditions	Yield
With potassium hydrogencarbonate In acetone at 20 - 25℃;	91.5%

1-bromoethyl acetate (40258-78-4) + cefuroxime (97232-97-8) → trans-cefuroxime axetil (97232-96-7)

Conditions	Yield
In N,N-dimethyl-formamide at 10℃; for 3h;	91.5%

1-bromoethyl acetate (40258-78-4) + (R)-ibuprofene (51146-57-7) → (R)-(-)-ibuprofen-1-acetoxy ethyl ester (1418602-98-8)

Conditions	Yield
With potassium hydrogencarbonate In acetone at 20 - 25℃;	91.4%

1-bromoethyl acetate (40258-78-4) + (S)-(+)-flurbiprofen (5104-49-4, 51543-38-5, 51543-39-6, 51543-40-9) → 2S-(+)-flurbiprofen axetil

Conditions	Yield
With N-benzyl-N,N,N-triethylammonium chloride; caesium carbonate In dichloromethane at 20℃; for 3h; Catalytic behavior; Reagent/catalyst; Solvent; Temperature;	90.9%
With N-ethyl-N,N-diisopropylamine In acetone at 0 - 25℃; for 12h; Reagent/catalyst; Solvent; Concentration; Temperature;	84.5%

1-bromoethyl acetate (40258-78-4) + ibuprofen (15687-27-1) → ibuprofen-1-acetoxy ethyl ester (1418602-97-7)

Conditions	Yield
With potassium hydrogencarbonate In acetone at 20 - 25℃; Temperature; Time; Large scale;	90.5%

1-bromoethyl acetate (40258-78-4) + ALPROSTADIL (745-65-3) → 1-acetoxyethyl-7-(1R,2R,3R,)-3-hydroxy-2(E)-3(S)-3-hydroxy-1-octenyl-5-oxo cyclopentyl heptanoate

Conditions	Yield
Stage #1: ALPROSTADIL With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile for 0.5h; Cooling with ice; Stage #2: 1-bromoethyl acetate In acetonitrile at 20℃; for 20h; Reagent/catalyst; Solvent; Concentration;	86.7%

1-bromoethyl acetate (40258-78-4) + combrestatin A4 (117048-62-1, 117048-59-6) → (Z)-ethyl-2-(2-methoxy-5-(3,4,5-trimethoxystyryl)phenoxy)acetate (1403383-57-2)

Conditions	Yield
With potassium carbonate In acetone for 8h; Reflux;	85%

1-bromoethyl acetate (40258-78-4) + 1-tert-butyl (S)-2-{(E)-(S)-1-[(S)-2-(4-but-2-ynyloxyphenyl)-1-methoxycarbonylethylcarbamoyl]-10-oxoheptadec-2-enyl}-2-hydroxysuccinate → 1-tert-butyl 4-(1-acetoxyethyl) (S)-2-{(E)-(S)-1-[(S)-2-(4-but-2-ynyloxyphenyl)-1-methoxycarbonyl-ethylcarbamoyl]-10-oxo-heptadec-2-enyl}-2-hydroxy-succinate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; sodium iodide In dichloromethane at 20℃; for 6h; Inert atmosphere;	81%

1-bromoethyl acetate (40258-78-4) + Ketorolac (74103-06-3) → 5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid-1-(acetoxy)ethyl ester

Conditions	Yield
With potassium carbonate In acetone at 20℃;	80%
With potassium carbonate In acetone at 20℃;	76%

1-bromoethyl acetate (40258-78-4) + (6R,7R)-7-[2-furanyl-(Z)-2-methoxyimino]acetamido-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid (69088-15-9) → (R)-cefuroxime 1-acetoxyethyl ester

Conditions	Yield
With copper dichloride In N,N-dimethyl acetamide at 2 - 20℃; for 1h;	77.6%

1-bromoethyl acetate (40258-78-4) + (1R,5S,6S)-2-[(1-(4-fluorobenzyl)azetidin-3-yl)thio]-6-[(R)-1-hydroxyethyl]-1-methyl-carbapen-2-em-3-carboxylic acid (878534-37-3) → 1-(acetoxy)ethyl (1R,5S,6S)-2-[(1-(4-fluorobenzyl)azetidin-3-yl)thio]-6-[(R)-1-hydroxyethyl]-1-methyl-carbapen-2-em-3-carboxylate (1158510-27-0)

Conditions	Yield
With tetrabutylammomium bromide; N-ethyl-N,N-diisopropylamine In ISOPROPYLAMIDE at 35℃; for 2h;	77%

1-bromoethyl acetate (40258-78-4) + 1-tert-butyl (S)-2-{(E)-(S)-1-[(S)-2-(4-but-2-ynyloxy-phenyl)-1-carboxy-ethylcarbamoyl]-10-oxo-heptadec-2-enyl}-2-hydroxy-succinate → C47H69NO14

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane for 19h; Inert atmosphere; Reflux;	75%

1-bromoethyl acetate (40258-78-4) + bezafibrate (41859-67-0) → C23H26ClNO6 (1415335-09-9)

Conditions	Yield
Stage #1: bezafibrate With sodium carbonate In N,N-dimethyl acetamide at 30℃; for 1h; Inert atmosphere; Stage #2: 1-bromoethyl acetate In N,N-dimethyl acetamide at 30℃; for 3.5h; Inert atmosphere;	74%

1-bromoethyl acetate (40258-78-4) + fenofibric acid (42017-89-0) → 2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropionic acid 1-acetoxyethyl ester (1319719-23-7)

Conditions	Yield
Stage #1: fenofibric acid With potassium carbonate In N,N-dimethyl acetamide at 32℃; for 1.5h; Inert atmosphere; Stage #2: 1-bromoethyl acetate In N,N-dimethyl acetamide at -5 - 30℃; for 1h; Inert atmosphere;	69%

1-bromoethyl acetate (40258-78-4) + 4-methyl (S)-2-{(E)-(S)-1-[(S)-2-(4-but-2-ynyloxy-phenyl)-1-methoxycarbonyl-ethylcarbamoyl]-10-oxo-heptadec-2-enyl}-2-hydroxy-succinate → 4-methyl 1-(1-acetoxy-ethyl) (S)-2-{(E)-(S)-1-[(S)-2-(4-but-2-ynyloxy-phenyl)-1-methoxycarbonyl-ethylcarbamoyl]-10-oxo-heptadec-2-enyl}-2-hydroxy-succinate

Conditions	Yield
With tetra-(n-butyl)ammonium iodide; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; Inert atmosphere;	68%

1-bromoethyl acetate (40258-78-4) + (S)-(+)-flurbiprofen (5104-49-4, 51543-38-5, 51543-39-6, 51543-40-9) → 2S-(+)-flurbiprofen axetil + C19H19FO4

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In toluene at 0 - 25℃; for 4h; Reagent/catalyst; Solvent;	A 63.4% B n/a

1-bromoethyl acetate (40258-78-4) + Lithium all-cis-cyclononatetraenid → Essigsaeure-(2,4,6,8-cyclononatetraenyl)methylester

Conditions	Yield
In tetrahydrofuran at -20℃; for 2h;	61%

1-bromoethyl acetate (40258-78-4) + 2-(4-(3-(4,5-dichloro-1-methyl-1H-indole-2-carboxamido)oxetan-3-yl)phenyl)-2-(pyridin-3-yl)acetic acid → 1-acetoxyethyl 2-(4-(3-(4,5-dichloro-1-methyl-1H-indole-2-carboxamido)oxetan-3-yl)phenyl)-2-(pyridin-3-yl)acetate

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 2h; Inert atmosphere;	54%

1-bromoethyl acetate (40258-78-4) + C15H18F3NO5 → C19H24F3NO7

Conditions	Yield
In acetone at 5 - 10℃; for 12h;	49%

1-bromoethyl acetate (40258-78-4) + Bumetanide (28395-03-1) → 1-[3-(butylamino)-4-phenoxy-5-sulfamoylbenzoyloxy]ethyl acetate

Conditions	Yield
With tetra-(n-butyl)ammonium iodide; potassium carbonate In N,N-dimethyl-formamide at 0 - 30℃; for 2h;	48.9%

1-bromoethyl acetate (40258-78-4) + C16H20F3NO5 → C20H26F3NO7

Conditions	Yield
With potassium carbonate In acetone at 5 - 10℃; for 12h;	42%

1-bromoethyl acetate (40258-78-4) + (S)-2-{(E)-(S)-1-[(S)-2-(4-but-2-ynyloxyphenyl)-1-methoxycarbonylethylcarbamoyl]-10-oxoheptadec-2-enyl}-2-hydroxysuccinic acid → 1-(1-acetoxy-ethyl) (S)-2-{(E)-(S)-1-[(S)-2-(4-but-2-ynyloxy-phenyl)-1-methoxycarbonyl-ethylcarbamoyl]-10-oxo-heptadec-2-enyl}-2-hydroxy-succinate

Conditions	Yield
With sodium hydrogencarbonate In tetrahydrofuran at 20℃; Inert atmosphere;	39%

1-bromoethyl acetate (40258-78-4) + 5-[4-(O2-ammonium diazen-1-ium-1,2-diolato)phenyl]-1-(4-methylsulfonylphenyl)-3-trifluoromethyl-1H-pyrazole → 5-[4-(O2-(1-acetoxyethyl)diazen-1-ium-1,2-diolato)phenyl]-1-(4-methylsulfonylphenyl)-3-trifluoromethyl-1H-pyrazole (1245272-97-2)

Conditions	Yield
With potassium carbonate In acetonitrile at 25℃; for 18h;	37%

1-bromoethyl acetate (40258-78-4) + N-Nitroethylamin-Kaliumsalz (67105-18-4) → N-(1-Acetoxyethoxy)-N'-ethyldiazen-N-oxid (92667-21-5)

Conditions	Yield
In acetonitrile for 18h; Ambient temperature;	32%

Upstream product

• 506-96-7 Acetyl bromide 
• 75-07-0 acetaldehyde 
• 123-63-7 paracetaldehyde 
• 108-05-4 vinyl acetate 
• 64-19-7 acetic acid 

Downstream Products

• 459430-99-0 ethyl (4-{4-(benzyloxy)-3-[(4-fluorophenyl)sulphonyl]benzyl}-3,5-dimethylphenoxy)acetate 
• 398136-94-2 [3-(N-(3-cyano-4-(4-hydroxypiperidin-1-yl)phenyl)carbamoyl)-5-fluoro-2-methylindol-1-yl]Acetic Acid 
• 256492-93-0 2-[2-(4-cyanophenyl)-ethyl]-3-methyl-6-[N-(ethoxycarbonylmethyl)-quinoline-8-sulphonylamino]-imidazo[4,5-b]pyridine 
• 60-29-7 diethyl ether 
• 108-20-3 di-isopropyl ether 
• 64544-07-6 cefuroxime axetil 
• 1245272-97-2 5-[4-(O₂-(1-acetoxyethyl)diazen-1-ium-1,2-diolato)phenyl]-1-(4-methylsulfonylphenyl)-3-trifluoromethyl-1H-pyrazole 
• 1245272-98-3 5-[4-(O₂-(1-acetoxyethyl)diazen-1-ium-1,2-diolato)phenyl]-1-(4-sulfamoylphenyl)-3-trifluoromethyl-1H-pyrazole 
• 1319719-23-7 2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropionic acid 1-acetoxyethyl ester 
• 1418602-97-7 ibuprofen-1-acetoxy ethyl ester 
• 1418602-98-8 (R)-(-)-ibuprofen-1-acetoxy ethyl ester 
• 1418602-99-9 (S)-(+)-ibuprofen-1-acetoxy ethyl ester 
• 91503-79-6 fluorbiprofen axetil 

Relevant articles and documents

Preparation method of high-optical-purity 2S-(+)-flurbiprofen axetil

The invention belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of high-optical-purity 2S (+) flurbiprofen axetil, which comprises the following steps: (1) reacting 2S (+) flurbiprofen with 1-bromoethyl acetate under the actions of inorganic alkali, an organic solvent and a phase transfer catalyst, and carrying out suction filtration, washing, drying and vacuum concentration to obtain an oily crude product; and performing column chromatography purification on the oily crude product to obtain a pure product. The product yield reaches 90% or above, the optical purity reaches 99.9% or above, and the product racemization problem in the preparation process is effectively solved.

Crystalline cefuroxime axetil preparation method

The invention relates to a crystalline cefuroxime axetil preparation method, which comprises: 1) carrying out a reaction on paraldehyde and acetyl bromide at a temperature of -10-10 DEG C under the action of a catalyst to obtain 1-bromoethyl acetate; 2) adding cefuroxime acid and a catalyst to the mixed solution of an organic solvent and water, adjusting the temperature to -20-5 DEG C, adding the1-bromoethyl acetate prepared in the step 1) to the mixed solution in a dropwise manner to obtain the crystalline cefuroxime axetil. According to the present invention, the method improves the traditional process, simplifies the process, improves the product quality, does not use the extraction solvent dichloromethane, greatly reduce the production cost, and improves the reaction efficiency and the purity of the final product.

Synthesis and biological evaluation of orally active hypolipidemic agents

A series of novel fenofibric acid ester prodrugs 1c-1h were synthesized and evaluated with the aim of obtaining potent hypolipidemic agents. Prodrugs 1c and 1d exhibited potent hypochlolesterolemic activity, lowering the mice plasma triglyceride level up to 47% in Swiss albino mice after oral administration of 50 mg/kg/day for 8 days. Fenofibric acid ester prodrugs 1c-1h were found lipophilic like fenofibrate (1b), indicated by partition coefficients measured in octanol-buffer system at pH 7.4. On the basis of in vivo studies, prodrugs 1c and 1d emerged as potent hypolipidemic agents.