638-41-5

Basic information

• Product Name: Pentyl chloroformate
• Synonyms: carbonochloridicacidpentylester;chlorocarbonicacidpentylester;CHLOROFORMIC ACID AMYL ESTER;CHLOROFORMIC ACID N-AMYL ESTER;CHLOROFORMIC ACID PENTYL ESTER;AMYL CHLOROFORMATE;PENTYL CHLOROFORMATE;N-PENTYL CHLOROFORMATE
• CAS NO: 638-41-5
• Molecular Formula: C₆H₁₁ClO₂
• Molecular Weight: 150.6
• EINECS: 211-336-4
• Mol File: 638-41-5.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 161 °C
• Flash Point: 53 °C
• Appearance: /
• Density: 1,04 g/cm3
• Vapor Pressure: 1.92mmHg at 25°C
• Refractive Index: 1.4181
• Storage Temp.: Refrigerator
• Solubility: Chloroform, Ethyl Acetate
• Water Solubility: 1.213g/L at 25℃
• CAS DataBase Reference: Pentyl chloroformate(CAS DataBase Reference)
• NIST Chemistry Reference: Pentyl chloroformate(638-41-5)
• EPA Substance Registry System: Pentyl chloroformate(638-41-5)

Safety Data

• Hazard Codes: C
• Statements: 10-23-34
• Safety Statements: 26-36-45-36/37/39
• RIDADR: 3277
• Hazardous Substances Data: 638-41-5(Hazardous Substances Data)

Usage

Uses

n-Pentyl Chloroformate is a chemical reagent used in the synthesis of intermediates for Capecitabine (C175650), an antineoplastic agent. As well as used for the synthesis of other pharmaceuticals such as dabigatran etexilate (D100150), a direct thrombin inhibitor.

InChI:InChI=1/C6H11ClO2/c1-2-3-4-5-9-6(7)8/h2-5H2,1H3

Synthetic route

pentan-1-ol (71-41-0) + bis(trichloromethyl) carbonate (32315-10-9) → pentyl chloroformate (638-41-5)

Conditions	Yield
With pyridine In dichloromethane at 20℃; for 2h;	85.6%
With triethylamine In tetrahydrofuran at 0 - 20℃; for 1h;
With triethylamine In tetrahydrofuran at 0 - 20℃; for 6.25h; Inert atmosphere;

phosgene (75-44-5) + pentan-1-ol (71-41-0) → pentyl chloroformate (638-41-5)

Conditions	Yield
With hydrogenchloride In 1,4-dioxane at 20℃; Rate constant; Mechanism; var. conc., without HCl;

pentyl chloroformate (638-41-5) + 1-t-Butoxycarbonylpiperazine (57260-71-6) → piperazine-1,4-dicarboxylic acid tert-butyl ester pentyl ester

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃;	100%

pentyl chloroformate (638-41-5) + C39H32FN3O8 → C45H42FN3O10

Conditions	Yield
With pyridine In dichloromethane at -15 - 0℃;	99.1%

pentyl chloroformate (638-41-5) → amyl azidoformate

Conditions	Yield
With sodium azide In acetone at 20℃;	98%

5-[1-(4-aminobenzyl)-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione (882007-15-0) + pentyl chloroformate (638-41-5) → 5-[1-(4-pentyloxycarbonylaminobenzyl)-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione

Conditions	Yield
With pyridine In dichloromethane at 0℃; for 1h;	97%

pentyl chloroformate (638-41-5) + 2,2,4,4-Tetramethyl-1,3-oxazolidine (57822-91-0) → pentyl 2,2,4,4-tetramethyl-1,3-oxazolidine-3-carboxylate

Conditions	Yield
With sodium carbonate In dichloromethane at 20℃; for 5h;	96%

Flucytosine (2022-85-7) + pentyl chloroformate (638-41-5) → (5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl)carbamic acid amyl ester (862508-03-0)

Conditions	Yield
With pyridine; tetrabutylammomium bromide In dichloromethane at 20℃; for 1.5h; Reagent/catalyst;	96%
With pyridine In dichloromethane at -10 - 20℃; for 2h; Concentration; Inert atmosphere;	94.3%
With pyridine	75%
With tetra(n-butyl)ammonium hydrogensulfate; triethylamine In chloroform; water at 5 - 10℃; for 1h;	300 g

pentyl chloroformate (638-41-5) + 5-chloro-N2-{5-methyl-4-(piperidin-4-yl)-2-[(propan-2-yl)oxy]phenyl}-N4-[2-(propane-2-sulfonyl)phenyl]pyrimidine-2,4-diamine (1032900-25-6) → pentyl 4-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidine-1-carboxylate

Conditions	Yield
With dmap In dichloromethane at 20℃;	96%

pentyl chloroformate (638-41-5) + (2R,3R,4R,5R)-2-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)-5-methyl-tetrahydrofuran-3,4-diyl diacetate (161599-46-8) → N1-(2',3'-di-O-acetyl-5'-deoxy-β-D-ribofuranosyl)-5-fluoro-N4-(pentyloxycarbonyl)cytosine (162204-20-8)

Conditions	Yield
With potassium phosphate In dichloromethane; isopropyl alcohol at 0 - 25℃; for 4h; Reagent/catalyst; Inert atmosphere;	94.2%
With pyridine In dichloromethane at 0℃; for 1h;	93%
With dmap; potassium carbonate In dichloromethane at 5℃; for 0.75h; Temperature; Solvent; Reagent/catalyst;	90.6%

pentyl chloroformate (638-41-5) + 2,3,4,5,6-pentafluorophenol (771-61-9) → pentyloxycarbonyl-pentafluorophenoxy (1332927-90-8)

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran at 0 - 5℃; for 2.5h;	94%

pentyl chloroformate (638-41-5) + 2',3'-isopropylidene adenosine (362-75-4) → 2',3'-O-isopropylidene-5'-O-pentyloxycarbonyladenosine

Conditions	Yield
With dmap In acetonitrile at 20℃; for 4h; Cooling with ice; Inert atmosphere;	93%

3,6-di-n-propyl-1,6-dihydro-s-tetrazine (13717-88-9) + pentyl chloroformate (638-41-5) → 3,6-dipropyl-6H-[1,2,4,5]tetrazine-1-carboxylic acid pentyl ester

Conditions	Yield
	92.9%

D-Threonine (632-20-2) + pentyl chloroformate (638-41-5) → (2R,3S)-3-hydroxy-2-{[(pentyloxy)carbonyl]amino}butanoic acid (1439367-11-9)

Conditions	Yield
With tetrabutylammomium bromide; sodium hydrogencarbonate In tetrahydrofuran; water at 20℃; for 18h;	90%
With tetrabutylammomium bromide; sodium hydrogencarbonate In tetrahydrofuran; water at 20℃; for 18h;	90%
With tetrabutylammomium bromide; sodium hydrogencarbonate In tetrahydrofuran; water at 20℃; for 18h;	90%

3,6-dimethyl-1,6-dihydro-1,2,4,5-tetrazine (13717-81-2) + pentyl chloroformate (638-41-5) → 3,6-dimethyl-6H-[1,2,4,5]tetrazine-1-carboxylic acid pentyl ester

Conditions	Yield
	89.4%

4-nitro-phenol (100-02-7) + pentyl chloroformate (638-41-5) → 4-nitrophenyl n-pentyl carbonate (67036-14-0)

Conditions	Yield
With triethylamine In tetrahydrofuran at 0 - 5℃; for 2.5h;	89%

pentyl chloroformate (638-41-5) + 2'3'-O-isopropylidene-5'-deoxy-5-fluorocytidine → 2'3'-O-isopropylidene-5'-deoxy-5-fluoro-N4-(pentyloxycarbonyl)cytidine

Conditions	Yield
With pyridine In dichloromethane at -5 - 5℃; for 0.5h;	88.2%

pentyl chloroformate (638-41-5) + 4,4'-diamino diphenyl methane (101-77-9) → dipentyl(methylene)bis(4,1-phenylene)dicarbamate (102894-35-9)

Conditions	Yield
With triethylamine In tetrahydrofuran at 0 - 50℃; for 4h;	88%

PD 0332991 (571190-30-2) + pentyl chloroformate (638-41-5) → pentyl 4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate

Conditions	Yield
With dmap In dichloromethane at 0 - 20℃;	87%

pentyl chloroformate (638-41-5) + methyl (3-(5-chloro-2-(2-chloro-4-(N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl) sulfamoyl)-5-fluorophenoxy)phenyl)propyl)glycinate → methyl N-(3-(5-chloro-2-(2-chloro-4-(N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)sulfamoyl)-5-fluorophenoxy)phenyl)propyl)-N-((pentyloxy)carbonyl)glycinate

Conditions	Yield
Stage #1: methyl (3-(5-chloro-2-(2-chloro-4-(N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl) sulfamoyl)-5-fluorophenoxy)phenyl)propyl)glycinate With triethylamine In dichloromethane at 20℃; for 0.166667h; Stage #2: pentyl chloroformate In dichloromethane at 80℃; for 12h;	86.9%
With triethylamine In dichloromethane at 80℃; for 12h;	0.6 g

pentyl chloroformate (638-41-5) + 5'-deoxy-5-fluorocytidine (66335-38-4) → C15H20FN3O7S (1309454-52-1)

Conditions	Yield
Stage #1: 5'-deoxy-5-fluorocytidine With pyridine; thionyl chloride In acetonitrile at -5 - 0℃; Stage #2: pentyl chloroformate In acetonitrile at -5 - 20℃;	85%

pentyl chloroformate (638-41-5) + C9H10FN3O5S (1309454-51-0) → C15H20FN3O7S (1309454-52-1)

Conditions	Yield
With pyridine In dichloromethane at -5 - 20℃;	85%

7-bromo-pyrrolo[2,1-f][1,2,4]triazin-4-ylamine (937046-98-5) + pentyl chloroformate (638-41-5) → pentyl (7-bromopyrrolo[2,1-f][1,2,4]triazin-4-yl)carbamate

Conditions	Yield
With pyridine In dichloromethane for 5h; Cooling with ice;	85%

pentyl chloroformate (638-41-5) + benzotriazol-1-ol (2592-95-2) → pentyloxycarbonyl-1-hydroxybenzotriazole

Conditions	Yield
Stage #1: benzotriazol-1-ol With triethylamine In tetrahydrofuran at 0 - 5℃; for 0.25h; Stage #2: pentyl chloroformate In tetrahydrofuran for 1.5h;	84%

pentyl chloroformate (638-41-5) + 2-amino-6-bromoquinoline (791626-58-9) → pentyl N-(6-bromo-2-quinolyl)carbamate

Conditions	Yield
With 1-methyl-1H-imidazole In dichloromethane at 0 - 25℃; for 12h;	84%

pentyl chloroformate (638-41-5) + 2-amino-1H-imidazole-4,5-dicarbonitrile (40953-34-2) → 2-amino-4,5-dicyano-imidazole-1-carboxylic acid pentyl ester (59717-41-8)

Conditions	Yield
With triethylamine In methanol; acetonitrile	83%

pentyl chloroformate (638-41-5) + (2R,3R,4R,5R)-2-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)-5-methyl-tetrahydrofuran-3,4-diyl diacetate (161599-46-8) → capecitabine (154361-50-9)

Conditions	Yield
With sodium hydroxide In water; acetone at 30℃; for 5h; Green chemistry;	82%
Stage #1: pentyl chloroformate; (2R,3R,4R,5R)-2-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)-5-methyl-tetrahydrofuran-3,4-diyl diacetate With pyridine In dichloromethane at 0℃; for 1h; Stage #2: With sodium hydroxide In ethanol; water at -5 - 0℃; for 0.233333h;	80.2%
Multi-step reaction with 2 steps 1: dichloromethane 2: sodium hydroxide / methanol View Scheme
Multi-step reaction with 2 steps 1: pyridine / dichloromethane / 1 h / 0 °C 2: sodium methylate / methanol / 1 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: potassium phosphate / isopropyl alcohol; dichloromethane / 4 h / 0 - 25 °C / Inert atmosphere 2: sodium hydroxide / methanol; water / 1 h / -10 - 5 °C / Autoclave View Scheme

pentyl chloroformate (638-41-5) + 5'-deoxy-5-fluorocytidine (66335-38-4) → capecitabine (154361-50-9)

Conditions	Yield
Stage #1: 5'-deoxy-5-fluorocytidine With pyridine; thionyl chloride In acetonitrile at -5 - 0℃; Stage #2: pentyl chloroformate In acetonitrile at -5 - 20℃;	80%

β-D-(2'S)-2'-deoxy-2'-fluoro-2'-C-methylcytidine + pentyl chloroformate (638-41-5) → β-D-(2'S)-2'-deoxy-2'-fluoro-2'-methyl-N4-pentyloxycarbonylcytidine

Conditions	Yield
With chloro-trimethyl-silane In pyridine at 20℃;	78%

4-(4-{6-amino-5-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester + pentyl chloroformate (638-41-5) → C32H40Cl2FN5O5

Conditions	Yield
In dichloromethane at 0 - 20℃; for 1h;	78%

pentyl chloroformate (638-41-5) + mitomycin-C (69515-74-8, 628317-17-9) → N1a-<(pentyloxy)carbonyl>mitomycin C (88700-50-9)

Conditions	Yield
With triethylamine In tetrahydrofuran for 0.25h;	77%

Upstream product

• 75-44-5 phosgene 
• 71-41-0 pentan-1-ol 
• 32315-10-9 bis(trichloromethyl) carbonate 

Downstream Products

• 7647-01-0 hydrogenchloride 
• 543-59-9 1-Chloropentane 
• 124-38-9 carbon dioxide 
• 109-68-2 2-pentene 
• 1133438-93-3 HS₅₇-6 
• 1263295-51-7 pentyl 4-(benzyl(methyl)amino)-5-fluoro-2-oxopyrimidine-1(2H)-carboxylate 
• 154361-50-9 capecitabine 
• 102894-35-9 dipentyl(methylene)bis(4,1-phenylene)dicarbamate 
• 5420-71-3 2-pentyloxycarbonyloxy-propionic acid-(2-butoxy-ethyl ester) 
• 6283-91-6 2-pentyloxycarbonyloxy-propionic acid pentyl ester 
• 83264-10-2 (4-hydroxy-phenyl)-carbamic acid pentyl ester 
• 638-42-6 pentyl carbamate 
• 107416-66-0 2-hydroxy-4-pentyloxycarbonylamino-benzoic acid 
• 100137-56-2 carbonic acid-(2-nitro-phenyl ester)-pentyl ester 

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The reaction of phosgene with alcohols is inhibited by hydrogen chloride.Here, as shown for the model methanolysis of methyl chloroformate, the halide ions have practically no effect on the reaction rate.The inhibition is due to the formation of associates, which do not possess nucleophilic characteristics between the alcohol and the hydrogen chloride.In proton-inert solvents at low temperatures the reaction only goes to the extent of a third on account of the formation of a stable unreactive 2:1 associate of the alcohol with hydrogen chloride.