1474-78-8

Basic information

• Product Name: Ethyl diethoxyphosphinylformate
• Synonyms: Diethyl carbethoxyphosphonate;Diethyl ethoxycarbonylphosphonate;Ethyl diethoxyphosphinecarboxylate oxide;Formic acid, phosphono-, triethyl ester;phosphinecarboxylicacid,diethoxy-,ethylester,oxide;Triethyl carboxyphosphonate;Triethyl phosphonomethanoate;(ETHOXYCARBONYL)PHOSPHONIC ACID DIETHYL ESTER
• CAS NO: 1474-78-8
• Molecular Formula: C₇H₁₅O₅P
• Molecular Weight: 210.16
• EINECS: 216-016-8
• Product Categories: Organic Building Blocks;Phosphonates/Phosphinates;Phosphorus Compounds
• Mol File: 1474-78-8.mol
• Article Data: 5

Chemical Properties

• Boiling Point: 135 °C12 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: /
• Density: 1.11 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.00947mmHg at 25°C
• Refractive Index: n20/D 1.423(lit.)
• Storage Temp.: Store below +30°C.
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• Stability: Moisture Sensitive
• BRN: 1781949
• CAS DataBase Reference: Ethyl diethoxyphosphinylformate(CAS DataBase Reference)
• NIST Chemistry Reference: Ethyl diethoxyphosphinylformate(1474-78-8)
• EPA Substance Registry System: Ethyl diethoxyphosphinylformate(1474-78-8)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38-43
• Safety Statements: 24/25-36/37-26-37-24
• WGK Germany: 3
• TSCA: Yes
• Hazardous Substances Data: 1474-78-8(Hazardous Substances Data)

Usage

Chemical Properties

Clear colorless to slightly yellow liquid

Uses

Diethyl (Ethoxycarbonyl)phosphonate is an impurity in the synthesis of Foscarnet (F727400), an inhibitor of viral DNA polymerase and reverse transcriptase. Foscarnet is used as an antiviral.

General Description

for synthesis

Purification Methods

Dissolve it in Et2O, shake this with H2O (to remove any trace of NaCl impurity), dry (Na2SO4), evaporate and distil it using an efficient fractionating column. [Nylén Chem Ber 57 1035 1924, Reetz et al. J Am Chem Soc 77 3813 1955, Monson Advanced Organic Synthesis Academic Press p 89 1972, Beilstein 3 II 103.]

InChI:InChI=1/C7H15O5P/c1-4-10-7(8)13(9,11-5-2)12-6-3/h4-6H2,1-3H3

Synthetic route

chloroformic acid ethyl ester (541-41-3) + triethyl phosphite (122-52-1) → triethyl phosphonoformate (1474-78-8)

Conditions	Yield
	91%

dimethoxymethyl phosphonic acid dimethyl ester (30410-95-8) → triethyl phosphonoformate (1474-78-8)

Conditions	Yield
With N-Bromosuccinimide In benzene for 1h; Heating; argon atmosphere;	80%

diethyl(diethoxymethyl)phosphonate (17997-33-0) → triethyl phosphonoformate (1474-78-8)

Conditions	Yield
With N-Bromosuccinimide In benzene for 1h; Heating;	80%
With di-tert-butyl peroxide In chlorobenzene at 120℃; Rate constant; Mechanism; Product distribution; various solvents, various temperature;

sodium diethyl phosphite (2303-76-6, 118080-94-7) + chloroformic acid ethyl ester (541-41-3) → triethyl phosphonoformate (1474-78-8)

Conditions	Yield
With diethyl ether
With Petroleum ether

ethanol (64-17-5) + N,N'-Bis-(O,O-diaethyl-phosphonocarbonyl)-sulfonyldiamid (20537-54-6) → triethyl phosphonoformate (1474-78-8)

Conditions	Yield
for 13h; Heating;

oxophosphonoacetic acid triethyl ester (16540-25-3) → triethyl phosphonoformate (1474-78-8)

Conditions	Yield
at 150℃;

Tris-aethoxycarbonyl-phosphorotrithioit (998-02-7) + chloroformic acid ethyl ester (541-41-3) → triethyl phosphonoformate (1474-78-8)

tris(ethoxythiocarbonyl) phosphorotrithioite (4373-18-6) + chloroformic acid ethyl ester (541-41-3) → triethyl phosphonoformate (1474-78-8)

diethyl <(ethylenedioxy)methyl>phosphonate (34909-25-6) → triethyl phosphonoformate (1474-78-8)

Conditions	Yield
With di-tert-butyl peroxide In chlorobenzene at 120℃; Rate constant; Mechanism; Product distribution; various solvents, various temperature;

triethyl phosphonoformate (1474-78-8) + 3-nitro-benzaldehyde (99-61-6) → (E)-ethyl 3-(3-nitrophenyl)acrylate (621-19-2)

Conditions	Yield
With lithium hydroxide In tetrahydrofuran at 20℃; Horner-Wadsworth-Emmons Olefination;	97%

triethyl phosphonoformate (1474-78-8) + 4-(2-nitrophenoxy)benzaldehyde (172932-06-8) → (E)-ethyl 3-[4-(2-nitrophenoxy)phenyl]acrylate

Conditions	Yield
Stage #1: triethyl phosphonoformate With 1,8-diazabicyclo[5.4.0]undec-7-ene; lithium chloride In acetonitrile at 20℃; for 1h; Horner-Wadsworth-Emmons Olefination; Stage #2: 4-(2-nitrophenoxy)benzaldehyde In acetonitrile at 20℃; for 18h; Horner-Wadsworth-Emmons Olefination;	94%

tert-butyl N-{4-[2-(4-formylphenoxy)ethyl]phenyl}carbamate (218139-11-8) + triethyl phosphonoformate (1474-78-8) → (E)-ethyl 3-{4-[2-(4-{[(tert-butoxy)carbonyl]amino}phenyl)ethoxy]phenyl}acrylate

Conditions	Yield
Stage #1: triethyl phosphonoformate With 1,8-diazabicyclo[5.4.0]undec-7-ene; lithium chloride In acetonitrile at 20℃; for 1h; Horner-Wadsworth-Emmons Olefination; Stage #2: tert-butyl N-{4-[2-(4-formylphenoxy)ethyl]phenyl}carbamate In acetonitrile at 20℃; for 18h; Horner-Wadsworth-Emmons Olefination;	91%

triethyl phosphonoformate (1474-78-8) → ethyl diethoxythiophosphorylformate

Conditions	Yield
With Lawessons reagent In toluene at 100℃; for 2h;	90%

triethyl phosphonoformate (1474-78-8) + 4-(4-nitrophenoxy)benzaldehyde (50961-54-1) → (E)-ethyl 3-[4-(4-nitrophenoxy)phenyl]acrylate

Conditions	Yield
Stage #1: triethyl phosphonoformate With 1,8-diazabicyclo[5.4.0]undec-7-ene; lithium chloride In acetonitrile at 20℃; for 1h; Horner-Wadsworth-Emmons Olefination; Stage #2: 4-(4-nitrophenoxy)benzaldehyde In acetonitrile at 20℃; for 18h; Horner-Wadsworth-Emmons Olefination;	90%

triethyl phosphonoformate (1474-78-8) → ethoxycarbonylphosphonic acid (55920-71-3)

Conditions	Yield
With trimethylsilyl bromide at 20℃;	89%
With trimethylsilyl bromide In tetrachloromethane at 0 - 20℃;
With trimethylsilyl bromide In tetrachloromethane at 20℃; for 16h;

triethyl phosphonoformate (1474-78-8) → disodium Ethoxycarbonylphosphonate (72305-00-1)

Conditions	Yield
With trimethylsilyl bromide; Amberlite IRC 50 (Na+ form) for 3h; Ambient temperature;	88%

C30H54O4S2Si2 (954106-06-0) + triethyl phosphonoformate (1474-78-8) → C31H54O6Si2 (954106-09-3)

Conditions	Yield
Stage #1: C30H54O4S2Si2 With 2,4,6-trimethyl-pyridine; methyl iodide In water; acetone at 67℃; for 13h; Stage #2: triethyl phosphonoformate With sodium hydride In tetrahydrofuran at -15 - 20℃; for 2h; Further stages.;	85%

triethyl phosphonoformate (1474-78-8) + cyclohexylamine (108-91-8) → diethyl (cyclohexylamino)carbonylphosphonate (174782-10-6)

Conditions	Yield
In acetonitrile at 20℃; for 20h;	80%

triethyl phosphonoformate (1474-78-8) → triethyl phosphate (78-40-0) + ethylphosphonic acid diethyl ester (78-38-6)

Conditions	Yield
at 395℃; for 8h;	A 79% B 8%

6,7-difluoro-1-trifluoromethyl-1,2,3,4-tetrahydro-4-oxoquinoline (852806-63-4) + triethyl phosphonoformate (1474-78-8) → ethyl 6,7-difluoro-1-trifluoromethyl-1,2,3,4-tetrahydro-4-oxo-3-quinolinecarboxylate (852806-64-5)

Conditions	Yield
Stage #1: 6,7-difluoro-1-trifluoromethyl-1,2,3,4-tetrahydro-4-oxoquinoline With sodium hydride In tetrahydrofuran at -78℃; Stage #2: triethyl phosphonoformate In tetrahydrofuran for 0.5h; Heating;	78%

4-(3-nitrophenoxy)benzaldehyde + triethyl phosphonoformate (1474-78-8) → (E)-ethyl 3-[4-(3-nitrophenoxy)phenyl]acrylate

Conditions	Yield
Stage #1: triethyl phosphonoformate With 1,8-diazabicyclo[5.4.0]undec-7-ene; lithium chloride In acetonitrile at 20℃; for 1h; Horner-Wadsworth-Emmons Olefination; Stage #2: 4-(m-nitrophenoxy)benzaldehyde In acetonitrile at 20℃; for 18h; Horner-Wadsworth-Emmons Olefination;	77%

triethyl phosphonoformate (1474-78-8) → sodium ethyl ethoxycarbonylphosphonate (72304-94-0)

Conditions	Yield
With sodium iodide In tetrahydrofuran for 120h;	76%

triethyl phosphonoformate (1474-78-8) + 7-(3,3-Dimethyl-2,4-dioxo-cyclopentyl)-hept-5-ynoic acid ethyl ester (87269-32-7) → 5-(6-Ethoxycarbonyl-hex-2-ynyl)-3,3-dimethyl-2,4-dioxo-cyclopentanecarboxylic acid ethyl ester (63315-07-1)

Conditions	Yield
With sodium hydride In dibutyl ether at 50 - 60℃;	70%

triethyl phosphonoformate (1474-78-8) + 3'-azido-2',3'-deoxythymidine (30516-87-1) → 3'-azido-3'-deoxythymidine 5'-(ethyl)(ethoxycarbonyl)phosphonate

Conditions	Yield
	68%

triethyl phosphonoformate (1474-78-8) + stavudin (3056-17-5) → 2'-3'-dideoxy-2',3'-didehydrothymidine 5'-(ethyl)(ethoxycarbonyl)phosphonate

Conditions	Yield
	65%

triethyl phosphonoformate (1474-78-8) + para-methylacetophenone (122-00-9) → ethyl (E)-3-p-tolylbut-2-enoate (6305-61-9, 115819-11-9, 94853-53-9)

Conditions	Yield
Stage #1: triethyl phosphonoformate With sodium hydride In tetrahydrofuran at 0℃; for 1.25h; Inert atmosphere; Stage #2: para-methylacetophenone In tetrahydrofuran for 20h; Inert atmosphere; Reflux;	61%

triethyl phosphonoformate (1474-78-8) + 2-Methylacetophenone (577-16-2, 122382-54-1) → (E)-ethyl 3-(2-methylphenyl)-but-2-enoate (100994-06-7)

Conditions	Yield
Stage #1: triethyl phosphonoformate With sodium hydride In tetrahydrofuran at 0℃; for 1.25h; Inert atmosphere; Stage #2: 2-Methylacetophenone In tetrahydrofuran for 20h; Inert atmosphere; Reflux;	59%

triethyl phosphonoformate (1474-78-8) + para-chloroacetophenone (99-91-2) → ethyl (E)-3-(4-chlorophenyl)-2-butenoate (21757-98-2, 81187-86-2)

Conditions	Yield
Stage #1: triethyl phosphonoformate With sodium hydride In tetrahydrofuran at 0℃; for 1.25h; Inert atmosphere; Stage #2: para-chloroacetophenone In tetrahydrofuran for 20h; Inert atmosphere; Reflux;	57%

triethyl phosphonoformate (1474-78-8) + 5-(tert-butyl-diphenyl-silanyloxymethyl)-5-formyl-benzoic acid (269411-93-0) → 5-(t-butyl-diphenyl-silanyloxymethyl)-5-(2-ethoxycarbonyl-vinyl)-benzoic acid

Conditions	Yield
With sodium hydride In DMF (N,N-dimethyl-formamide) at 0 - 23℃;	51%

3,3-dimethyl-butan-2-one (75-97-8) + triethyl phosphonoformate (1474-78-8) → (E)-3,4,4-trimethyl-1-pent-2-enoic acid ethyl ester (21016-48-8, 91140-23-7, 16812-82-1)

Conditions	Yield
Stage #1: triethyl phosphonoformate With sodium hydride In tetrahydrofuran at 0℃; for 1.25h; Inert atmosphere; Stage #2: 3,3-dimethyl-butan-2-one In tetrahydrofuran for 20h; Inert atmosphere; Reflux;	47%

triethyl phosphonoformate (1474-78-8) + benzylamine (100-46-9) → C12H18NO4P

Conditions	Yield
at 20℃; for 2h; Substitution;	36%

triethyl phosphonoformate (1474-78-8) + 1-(4-methoxyphenyl)ethanone (100-06-1) → (E)-ethyl 3-(4-methoxyphenyl)but-2-enoate (7706-82-3)

Conditions	Yield
Stage #1: triethyl phosphonoformate With sodium hydride In tetrahydrofuran at 0℃; for 1.25h; Inert atmosphere; Stage #2: 1-(4-methoxyphenyl)ethanone In tetrahydrofuran for 20h; Inert atmosphere; Reflux;	35%

triethyl phosphonoformate (1474-78-8) + 2,2-dimethylpropiophenone (938-16-9) → (Z)-ethyl 4,4-dimethyl-3-phenylpent-2-enoate (77920-99-1)

Conditions	Yield
Stage #1: triethyl phosphonoformate With sodium hydride In tetrahydrofuran at 0℃; for 1.25h; Inert atmosphere; Stage #2: 2,2-dimethylpropiophenone In tetrahydrofuran for 20h; Inert atmosphere; Reflux;	29%

triethyl phosphonoformate (1474-78-8) + Cyclohexyl phenyl ketone (712-50-5) → ethyl (2E)-3-cyclohexyl-3-phenyl prop-2-enoate (87666-40-8)

Conditions	Yield
Stage #1: triethyl phosphonoformate With sodium hydride In tetrahydrofuran at 0℃; for 1.25h; Inert atmosphere; Stage #2: Cyclohexyl phenyl ketone In tetrahydrofuran for 20h; Inert atmosphere; Reflux;	29%

triethyl phosphonoformate (1474-78-8) + 4-methyl-2-pentanone (108-10-1) → (2E)-ethyl 3,5-dimethyl-2-hexenoate (16812-83-2)

Conditions	Yield
Stage #1: triethyl phosphonoformate With sodium hydride In tetrahydrofuran at 0℃; for 1.25h; Inert atmosphere; Stage #2: 4-methyl-2-pentanone In tetrahydrofuran for 20h; Inert atmosphere; Reflux;	20%

Upstream product

• 34909-25-6 diethyl <(ethylenedioxy)methyl>phosphonate 
• 17997-33-0 diethyl(diethoxymethyl)phosphonate 
• 30410-95-8 dimethoxymethyl phosphonic acid dimethyl ester 
• 4373-18-6 tris(ethoxythiocarbonyl) phosphorotrithioite 
• 541-41-3 chloroformic acid ethyl ester 
• 998-02-7 Tris-aethoxycarbonyl-phosphorotrithioit 
• 16540-25-3 oxophosphonoacetic acid triethyl ester 
• 64-17-5 ethanol 
• 20537-54-6 N,N'-Bis-(O,O-diaethyl-phosphonocarbonyl)-sulfonyldiamid 
• 122-52-1 triethyl phosphite 
• 2303-76-6 sodium diethyl phosphite 

Downstream Products

• 42762-99-2 1-Diaethoxyphosphinyl-4-phenyl-cyclohexanol 
• 93-89-0 benzoic acid ethyl ester 
• 86119-84-8 phosphoric acid 
• 15719-64-9 methylammonium carbonate 
• 954106-09-3 C₃₁H₅₄O₆Si₂ 
• 174782-10-6 diethyl (cyclohexylamino)carbonylphosphonate 
• 72305-00-1 Disodium Ethoxycarbonylphosphonate 
• 77920-99-1 (Z)-ethyl 4,4-dimethyl-3-phenylpent-2-enoate 
• 87666-40-8 ethyl (2E)-3-cyclohexyl-3-phenyl prop-2-enoate 
• 6305-61-9 ethyl (E)-3-p-tolylbut-2-enoate 
• 7706-82-3 (E)-ethyl 3-(4-methoxyphenyl)but-2-enoate 
• 21757-98-2 ethyl (E)-3-(4-chlorophenyl)-2-butenoate 
• 100994-06-7 (E)-ethyl 3-(2-methylphenyl)-but-2-enoate 
• 81826-91-7 ethyl (E)-3-(naphthalen-2-yl)but-2-enoate 

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