3084-40-0

Basic information

• Product Name: Diethyl (hydroxymethyl)phosphonate
• Synonyms: (Hydroxymethyl)phosphonic acid, diethyl ester;(hydroxymethyl)-phosphonicacidiethylester;Phosphonic acid, (hydroxymethyl)-, diethyl ester;AURORA KA-1421;DIETHYL HYDROXYMETHYLPHOSPHONATE;4-Hydroxymethyldiethylphosphonate;DIETHYL (HYDROXYMETHYL)PHOSPHONATE, TECH .;Diethyl Phosphonometanol
• CAS NO: 3084-40-0
• Molecular Formula: C₅H₁₃O₄P
• Molecular Weight: 168.13
• EINECS: 221-391-6
• Product Categories: C-C Bond Formation;Horner-Wadsworth-Emmons Reagents;Olefination
• Mol File: 3084-40-0.mol
• Article Data: 44

Chemical Properties

• Boiling Point: 124-126 °C3 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: Clear colorless to yellow/Viscous Liquid
• Density: 1.14 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.00699mmHg at 25°C
• Refractive Index: n20/D 1.444(lit.)
• Storage Temp.: 0-10°C
• PKA: 13.00±0.10(Predicted)
• Water Solubility: 500g/L at 20℃
• CAS DataBase Reference: Diethyl (hydroxymethyl)phosphonate(CAS DataBase Reference)
• NIST Chemistry Reference: Diethyl (hydroxymethyl)phosphonate(3084-40-0)
• EPA Substance Registry System: Diethyl (hydroxymethyl)phosphonate(3084-40-0)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 37/39-26-36-37
• WGK Germany: 3
• TSCA: Yes
• Hazardous Substances Data: 3084-40-0(Hazardous Substances Data)

Usage

Chemical Properties

Clear colorless to yellow viscous liquid

Uses

Diethyl hydroxymethylphosphonate acts as a reactant for synthesis of α And β-dialkoxyphosphoryl isothiocyanate used in antiproliferative studies, dendritic polyglycerol anions for L-selectin inhibition, phosphonates for anti-HIV-1 activity, homo and copolymers of phosphonated norbornenes, Mitsunobu reactions. It is involved in studies of FBPase inhibition by phosphonic acid-containing thaizoles.

InChI:InChI=1/C5H13O4P/c1-3-8-10(7,5-6)9-4-2/h6H,3-5H2,1-2H3

Synthetic route

formaldehyd (50-00-0) + phosphonic acid diethyl ester (762-04-9) → diethyl (1-hydroxymethyl)phosphonate (3084-40-0)

Conditions	Yield
With triethylamine at 90℃; for 3h; Reflux;	96%
With potassium carbonate In ethanol at 75℃; for 5h;	95%
With potassium carbonate In toluene at 60℃; for 2.25h; pH=7.5 - 8;	95%

(diethoxyphosphoryl)methyl acetate (7016-78-6) → diethyl (1-hydroxymethyl)phosphonate (3084-40-0)

Conditions	Yield
With sodium ethanolate In ethanol	90%

formaldehyd (50-00-0) + Diethyl phosphonate (762-04-9, 123-22-8) → diethyl (1-hydroxymethyl)phosphonate (3084-40-0)

Conditions	Yield
triethylamine Ambient temperature;	85.5%
With triethylamine at 90℃; for 12h;	60%
With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride In dichloromethane; water for 1h; Ambient temperature;	53%
With triethylamine In toluene at 70℃; for 2h;

N-methoxypyridinium p-toluenesulfonate (53920-49-3) + phosphonic acid diethyl ester (762-04-9) → diethyl (1-hydroxymethyl)phosphonate (3084-40-0) + diethyl pyridin-2-yl-2-phosphonate (23081-78-9)

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile for 0.0833333h;	A 20% B 74%

Diethyl phosphonate (762-04-9, 123-22-8) → diethyl (1-hydroxymethyl)phosphonate (3084-40-0)

Conditions	Yield
With nitrogen; triethylamine; paraformaldehyde	60%
With nitrogen; triethylamine; paraformaldehyde	60%
With triethylamine; paraformaldehyde	57.5 g (68%)

formaldehyd (50-00-0) + 4-methoxy-aniline (104-94-9) + triethyl phosphite (122-52-1) → diethyl (1-hydroxymethyl)phosphonate (3084-40-0) + diethyl ester of p-N-methoxyphenylaminomethylphosphonic acid (81439-58-9) + 1,3,5-tris-(4-methoxybenzyl)-1,3,5-triazinane

Conditions	Yield
In xylene at 120℃; for 1h;	A 16% B 55% C 5.5%

trioxa-4,10,16-triaza-1,7,13-cyclooctadecane (296-38-8) + formaldehyd (50-00-0) + phosphonic acid diethyl ester (762-04-9) → diethyl (1-hydroxymethyl)phosphonate (3084-40-0) + [10,16-bis-(diethoxy-phosphorylmethyl)-1,7,13-trioxa-4,10,16-triaza-cyclooctadec-4-ylmethyl]-phosphonic acid diethyl ester

Conditions	Yield
With triethylamine In benzene Alkylation; Mannich reaction; substitution; Heating;	A n/a B 37%

formaldehyd (50-00-0) + p-aminoethylbenzoate (94-09-7) → diethyl (1-hydroxymethyl)phosphonate (3084-40-0) + p-N,N-diethylaminobenzoic acid ethyl ester (10287-54-4) + diethyl 4,4′-(methylenebis(azanediyl))dibenzoate (74763-68-1) + Diethyl (p-ethoxycarbonylphenylaminomethyl)phosphonate (114416-19-2)

Conditions	Yield
With triethyl phosphite In toluene at 110 - 120℃; for 6.5h;	A 32.8% B n/a C 24.4% D 23.8%

formaldehyd (50-00-0) + p-aminoethylbenzoate (94-09-7) + triethyl phosphite (122-52-1) → diethyl (1-hydroxymethyl)phosphonate (3084-40-0) + p-N,N-diethylaminobenzoic acid ethyl ester (10287-54-4) + diethyl 4,4′-(methylenebis(azanediyl))dibenzoate (74763-68-1) + Diethyl (p-ethoxycarbonylphenylaminomethyl)phosphonate (114416-19-2)

Conditions	Yield
In toluene at 110 - 120℃; for 6.5h;	A 32.8% B n/a C 24.4% D 23.8%

formaldehyd (50-00-0) + triethyl phosphite (122-52-1) → diethyl (1-hydroxymethyl)phosphonate (3084-40-0)

Conditions	Yield
With 2-methoxy-phenylamine

trioxa-4,10,16-triaza-1,7,13-cyclooctadecane (296-38-8) + formaldehyd (50-00-0) + triethyl phosphite (122-52-1) → diethyl (1-hydroxymethyl)phosphonate (3084-40-0) + [10,16-bis-(diethoxy-phosphorylmethyl)-1,7,13-trioxa-4,10,16-triaza-cyclooctadec-4-ylmethyl]-phosphonic acid diethyl ester

Conditions	Yield
Alkylation; Arbuzov reaction; substitution;

diiodomethane (75-11-6) + potassium salt of phosphoric acid diethyl ester → diethyl (1-hydroxymethyl)phosphonate (3084-40-0)

Conditions	Yield
With ethanol (90 percent )

diiodomethane (75-11-6) + ethanol (64-17-5) + potassium salt of phosphorous acid diethyl ester → diethyl (1-hydroxymethyl)phosphonate (3084-40-0)

formaldehyd (50-00-0) + bis(phthalimidylethyl)amine (63563-83-7) + phosphonic acid diethyl ester (762-04-9) → diethyl (1-hydroxymethyl)phosphonate (3084-40-0) + ({bis-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-amino}-methyl)-phosphonic acid diethyl ester

Conditions	Yield
In ethanol; toluene for 12h; Heating; Title compound not separated from byproducts.;

paraformaldehyde powder + Diethyl phosphonate (762-04-9, 123-22-8) → diethyl (1-hydroxymethyl)phosphonate (3084-40-0)

Conditions	Yield
With triethylamine
N-ethyl-N,N-diisopropylamine

1,2-dimethoxyethane (110-71-4) + phosphonic acid diethyl ester (762-04-9) → diethyl (1-hydroxymethyl)phosphonate (3084-40-0) + diethyl 1-hydroxy-2-methoxyethylphosphonate (19462-41-0)

Conditions	Yield
With tert.-butylhydroperoxide; potassium carbonate; copper dichloride In decane at 80℃; for 24h; Inert atmosphere; Overall yield = 53 %; Overall yield = 72 %Spectr.;

2-ethoxy-2,3-dihydro-4H-pyran (103-75-3) + diethyl (1-hydroxymethyl)phosphonate (3084-40-0) → (6-Ethoxy-tetrahydro-pyran-2-yloxymethyl)-phosphonic acid diethyl ester

Conditions	Yield
With hydrogenchloride	98.3%

diethyl (1-hydroxymethyl)phosphonate (3084-40-0) + trifluoromethylsulfonic anhydride (358-23-6) → (diethoxyphosphinyl)methyl trifluoromethanesulfonate (106938-62-9)

Conditions	Yield
With 2,6-dimethylpyridine In dichloromethane	98%
Stage #1: diethyl (1-hydroxymethyl)phosphonate With 2,6-dimethylpyridine In dichloromethane at -50℃; for 0.0833333h; Inert atmosphere; Stage #2: trifluoromethylsulfonic anhydride In dichloromethane at -50℃; for 0.333333h;	92.4%
With pyridine In dichloromethane at -78℃; for 3h;	90%

diethyl (1-hydroxymethyl)phosphonate (3084-40-0) + p-toluenesulfonyl chloride (98-59-9) → diethyl (p-toluenesulfonyloxymethane)phosphonate (31618-90-3)

Conditions	Yield
With triethylamine In diethyl ether	97%
In water at 3 - 35℃; for 14.5h; Temperature;	95.4%
With triethylamine In dichloromethane at 20℃; for 4h; Inert atmosphere;	92%

diethyl (1-hydroxymethyl)phosphonate (3084-40-0) → ethyl lithium hydroxymethylphosphonate

Conditions	Yield
With lithium bromide In various solvent(s) at 80℃; for 0.5h;	97%

2-butoxy-(2H)-3,4-dihydropyran (332-19-4) + diethyl (1-hydroxymethyl)phosphonate (3084-40-0) → (6-Butoxy-tetrahydro-pyran-2-yloxymethyl)-phosphonic acid diethyl ester

Conditions	Yield
With hydrogenchloride	96.9%

2-Chloro-4H-1,3,2-benzodioxaphosphorin-4-one (5381-99-7) + diethyl (1-hydroxymethyl)phosphonate (3084-40-0) → (4-Oxo-4H-benzo[1,3,2]dioxaphosphinin-2-yloxymethyl)-phosphonic acid diethyl ester (140383-34-2)

Conditions	Yield
With triethylamine In diethyl ether for 2h;	95%

diethyl (1-hydroxymethyl)phosphonate (3084-40-0) + 3-Chloro-2-methylpropene (563-47-3) → diethyl (4-methyl-2-oxa-4-pentenyl)phosphonate (108070-91-3)

Conditions	Yield
Stage #1: diethyl (1-hydroxymethyl)phosphonate With sodium hydride In tetrahydrofuran at 20℃; for 0.5h; Stage #2: 3-Chloro-2-methylpropene In tetrahydrofuran for 1h;	95%

2-methylprop-1-enyl chloride (513-37-1) + diethyl (1-hydroxymethyl)phosphonate (3084-40-0) → diethyl (4-methyl-2-oxa-4-pentenyl)phosphonate (108070-91-3)

Conditions	Yield
With sodium hydride In tetrahydrofuran at 20℃; for 1h;	95%

aminoethylpiperazine (140-31-8) + diethyl (1-hydroxymethyl)phosphonate (3084-40-0) → C11H26N3O3P

Conditions	Yield
at 0 - 40℃; for 1h;	95%

diethyl (1-hydroxymethyl)phosphonate (3084-40-0) + zinc(II) acetate dihydrate (5970-45-6) → Zn(2+)*HOCH2PO3(2-)=Zn(O3PCH2OH)

Conditions	Yield
In water to soln. Zn(OAc)2*2H2O in water was added HOCH2P(O)(OEt)2, mixt. was stirred for 30 min, transfeed into autoclave and heated at 160°C for48 h; solid was filtered and washed with water; elem. anal.;	94%

3,4-dihydro-2H-pyran (110-87-2) + diethyl (1-hydroxymethyl)phosphonate (3084-40-0) → diethyl <<(2-tetrahydropyranyl)oxy>methyl>phosphonate (71885-51-3)

Conditions	Yield
With trichlorophosphate In diethyl ether at 20℃; for 3h;	93%
With hydrogenchloride	90.6%

diethyl (1-hydroxymethyl)phosphonate (3084-40-0) + (2'R)-1-(2,3-dihydrofuran-2-yl)thymine (37076-62-3) → (2'R,3'S,5'R)-1-(2-diethoxyphosphinoylmethoxy-3-iodotetrahydrofuran-5-yl)thymine

Conditions	Yield
With iodine(I) bromide In dichloromethane at -25℃; for 0.833333h;	92%

diethyl (1-hydroxymethyl)phosphonate (3084-40-0) + Methacryloyl chloride (920-46-7) → Methacrylsaeure-diaethoxy-phosphinylmethylester (60161-88-8)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere;	91%
With triethylamine; copper(l) chloride

diethyl (1-hydroxymethyl)phosphonate (3084-40-0) + p-toluenesulfonyl chloride (98-59-9) → magnesium para-toluenesulfonate + diethyl (p-toluenesulfonyloxymethane)phosphonate (31618-90-3)

Conditions	Yield
With magnesium carbonate In water at 65℃; for 20h;	A n/a B 91%

N-hydroxyphthalimide (524-38-9) + diethyl (1-hydroxymethyl)phosphonate (3084-40-0) → diethyl (N-phthalimidyl)oxymethylphosphonate (81342-57-6)

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0℃; for 1h;	90%
With diethyl azodicarbonate; triphenylphosphine In tetrahydrofuran Ambient temperature;	70.2%
With triphenylphosphine; diethylazodicarboxylate

pyrocatechol phosphorochloridite (1641-40-3) + diethyl (1-hydroxymethyl)phosphonate (3084-40-0) → 2-(α-diethoxyphosphinoylmethoxy)-4,5-benzo-1,3,2-dioxaphospholane

Conditions	Yield
With triethylamine In benzene at 5 - 10℃;	90%

diethyl (1-hydroxymethyl)phosphonate (3084-40-0) + methanesulfonyl chloride (124-63-0) → diethyl <<(methylsulfonyl)oxy>methyl>phosphonate (114108-84-8)

Conditions	Yield
With triethylamine In dichloromethane at -10 - 20℃; for 2h;	90%
With triethylamine In toluene at 0 - 20℃;	89%
With triethylamine In dichloromethane at 0 - 20℃;	80%

2,3-dihydro-2H-furan (1191-99-7) + diethyl (1-hydroxymethyl)phosphonate (3084-40-0) → O,O-diethyl(2-tetrahydrofuranyloxy)methyl phosphonate (79872-66-5)

Conditions	Yield
With hydrogenchloride	88.9%

diethyl (1-hydroxymethyl)phosphonate (3084-40-0) + 3-nitrobenzoic acid (121-92-6) → (diethoxyphosphoryl)methyl 3-nitrobenzoate

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 18h;	87.1%

diethyl (1-hydroxymethyl)phosphonate (3084-40-0) → diethyl (azidomethyl)phosphonate (17982-55-7)

Conditions	Yield
With tris-(2-chloro-ethyl)-amine; triphenylphosphine; diethylazodicarboxylate In dichloromethane; benzene 0 deg C, 30 min to r.t., 20 h;	87%
With ammonia; triphenylphosphine; diethylazodicarboxylate In dichloromethane for 20h;
With tris-(2-chloro-ethyl)-amine; triphenylphosphine; diethylazodicarboxylate In dichloromethane for 20h;

diethyl (1-hydroxymethyl)phosphonate (3084-40-0) → diethyl chloromethylphosphonate (3167-63-3)

Conditions	Yield
With tetrachloromethane; triphenylphosphine for 8h; Heating;	86%
With tetrachloromethane; triphenylphosphine Appel reaction;	77%
With thionyl chloride In benzene

diethyl (1-hydroxymethyl)phosphonate (3084-40-0) + 4-Nitrobenzenesulfonyl chloride (98-74-8) → diethyl (4-nitrobenzenesulfonyloxy)methylphosphonate (294202-81-6)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	85%
With triethylamine In dichloromethane at 0 - 25℃;

6-methoxybenzofuran-2-carboxylic acid (50551-61-6) + diethyl (1-hydroxymethyl)phosphonate (3084-40-0) → (diethoxyphosphoryl)methyl 6-methoxybenzofuran-2-carboxylate

Conditions	Yield
Stage #1: 6-methoxybenzofuran-2-carboxylic acid With diisopropyl-carbodiimide In dichloromethane at 20℃; for 1h; Stage #2: diethyl (1-hydroxymethyl)phosphonate With dmap In dichloromethane for 6h; Reflux;	85%

diethyl (1-hydroxymethyl)phosphonate (3084-40-0) + 1,2-O-isopropylidene-5-methyl-5-deoxy-α-D-xylofuranose (4152-79-8, 33156-02-4, 37105-87-6, 37105-91-2, 37105-93-4, 53597-97-0, 97059-40-0) → 5-deoxy-3-O-(diethylphosphonomethyl)-1,2-O-isopropylidenyl-D-xylose

Conditions	Yield
With sodium hydride In mineral oil at 0 - 20℃; for 6h; Inert atmosphere;	83%

diethyl (1-hydroxymethyl)phosphonate (3084-40-0) + ortho-nitrobenzoic acid (552-16-9) → (diethoxyphosphoryl)methyl 2-nitrobenzoate

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 18h;	82.8%

diethyl (1-hydroxymethyl)phosphonate (3084-40-0) + 5,6-dimethoxyindole-2-carboxylic acid (88210-96-2) → C16H22NO7P

Conditions	Yield
Stage #1: 5,6-dimethoxyindole-2-carboxylic acid With diisopropyl-carbodiimide In dichloromethane at 20℃; for 1h; Stage #2: diethyl (1-hydroxymethyl)phosphonate With dmap In dichloromethane for 6h; Reflux;	82%

6-methoxy-1-benzothiophene-2-carboxylic acid (102539-79-7) + diethyl (1-hydroxymethyl)phosphonate (3084-40-0) → (diethoxyphosphoryl)methyl 6-methoxybenzothiophene-2-carboxylate

Conditions	Yield
Stage #1: 6-methoxybenzo[b]thiophene-2-carboxylic acid With diisopropyl-carbodiimide In dichloromethane at 20℃; for 1h; Stage #2: diethyl (1-hydroxymethyl)phosphonate With dmap In dichloromethane for 5h; Reflux;	81%

Upstream product

• 50-00-0 formaldehyd 
• 762-04-9 phosphonic acid diethyl ester 
• 762-04-9 Diethyl phosphonate 
• 104-94-9 4-methoxy-aniline 
• 122-52-1 triethyl phosphite 
• 296-38-8 trioxa-4,10,16-triaza-1,7,13-cyclooctadecane 
• 75-11-6 diiodomethane 
• 64-17-5 ethanol 
• 94-09-7 p-aminoethylbenzoate 
• 7016-78-6 (diethoxyphosphoryl)methyl acetate 
• 110-71-4 1,2-dimethoxyethane 
• 63563-83-7 bis(phthalimidylethyl)amine 
• 53920-49-3 N-methoxypyridinium p-toluenesulfonate 

Downstream Products

• 3167-63-3 diethyl chloromethylphosphonate 
• 2617-47-2 hydroxymethylphosphonic acid 
• 35449-96-8 (Di-ethoxyphosphinyl)-methyl-m-nitrophenylsulfonat 
• 33512-26-4 diethyl (phthalimidomethyl)phosphonate 
• 17982-55-7 diethyl (azidomethyl)phosphonate 
• 1660-94-2 Tetraethyl methylenediphosphonate 
• 114108-84-8 diethyl <<(methylsulfonyl)oxy>methyl>phosphonate 
• 116384-53-3 [[2-(6-amino-9H-purine-9-yl)ethoxy]methyl]phosphonic acid diethyl ester 
• 180587-75-1 (R)-diethyl (((1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphonate 
• 52378-69-5 diethyl (E)-cinnamylphosphonate 
• 52221-91-7 diethyl 3-phenylpropyl-1-phosphonate 
• 54553-21-8 diethyl 2-phenylethylphosphonate 
• 1018-24-2 diethyl styrylphosphonate 
• 25362-01-0 (Z)-diethyl styrylphosphonate 

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