4202-14-6

Basic information

• Product Name: Dimethyl acetylmethylphosphonate
• Synonyms: PHOSPHONIC ACID, (2-OXOPROPYL)-, DIMETHYL ESTER;(2-OXOPROPYL)PHOSPHONIC ACID DIMETHYL ESTER;ACETONYLPHOSPHONIC ACID DIMETHYL ESTER;LABOTEST-BB LT00847718;DIMETHYL (2-OXOPROPYL)PHOSPHONATE;DIMETHYL ACETONYLPHOSPHONATE;DIMETHYL ACETYLMETHYLPHOSPHONATE;Acetylmethylphosphonic acid dimethyl ester~Dimethyl acetonylphosphonate~Dimethyl (2-oxopropyl)phosphonate
• CAS NO: 4202-14-6
• Molecular Formula: C₅H₁₁O₄P
• Molecular Weight: 166.11
• EINECS: 224-110-5
• Product Categories: Horner-Emmons Reaction;Synthetic Organic Chemistry;Wittig & Horner-Emmons Reaction
• Mol File: 4202-14-6.mol
• Article Data: 27

Chemical Properties

• Boiling Point: 76-79 °C3 mm Hg(lit.)
• Flash Point: 200 °F
• Appearance: Clear colorless to light brown/Liquid
• Density: 1.202 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.0793mmHg at 25°C
• Refractive Index: n20/D 1.439(lit.)
• Storage Temp.: 2-8°C
• Solubility: Difficult to mix.
• BRN: 1766218
• CAS DataBase Reference: Dimethyl acetylmethylphosphonate(CAS DataBase Reference)
• NIST Chemistry Reference: Dimethyl acetylmethylphosphonate(4202-14-6)
• EPA Substance Registry System: Dimethyl acetylmethylphosphonate(4202-14-6)

Safety Data

• Hazard Codes: Xi
• Safety Statements: 23-24/25
• WGK Germany: 3
• F: 10
• Hazardous Substances Data: 4202-14-6(Hazardous Substances Data)

Usage

Chemical Properties

CLEAR COLOURLESS TO LIGHT BROWN LIQUID

Uses

Different sources of media describe the Uses of 4202-14-6 differently. You can refer to the following data:
1. Dimethyl acetylmethylphosphonate is a Reagent used together with tosyl azide in a one-pot alkynylation of aldehydes.
2. Reagent used together with tosyl azide in a one-pot alkynylation of aldehydes.

Synthesis Reference(s)

Tetrahedron Letters, 17, p. 2829, 1976 DOI: 10.1016/S0040-4039(01)85513-1

InChI:InChI=1/C5H11O4P/c1-5(6)4-10(7,8-2)9-3/h4H2,1-3H3

Synthetic route

chloroacetone (78-95-5) + phosphorous acid trimethyl ester (121-45-9) → dimethyl (2-oxopropyl)phosphonate (4202-14-6)

Conditions	Yield
In toluene at 135℃; under 3750.38 - 15001.5 Torr; for 0.333333h; Arbuzov Reaction; Large scale;	88%
Stage #1: chloroacetone With potassium iodide In acetone; acetonitrile at 20℃; for 2h; Stage #2: phosphorous acid trimethyl ester In acetone; acetonitrile at 50℃; for 24h;	82%
Stage #1: chloroacetone With potassium iodide In acetone; acetonitrile at 20℃; for 2h; Irradiation; Stage #2: phosphorous acid trimethyl ester In acetone; acetonitrile at 50℃; for 24h;	77%

[2-(Methoxycarbonyl-hydrazono)-propyl]-phosphonic acid dimethyl ester (103517-85-7, 103538-61-0) → dimethyl (2-oxopropyl)phosphonate (4202-14-6)

Conditions	Yield
With hydrogenchloride; acetone for 3h; Ambient temperature;	82%

iodoacetone (3019-04-3) + phosphorous acid trimethyl ester (121-45-9) → dimethyl (2-oxopropyl)phosphonate (4202-14-6)

Conditions	Yield
In toluene for 2h; Heating;	74%
In benzene
In acetone; acetonitrile at 20℃; for 12h; Michaelis-Arbuzov reaction;	101.3 g
In acetone; acetonitrile at 20 - 50℃; Inert atmosphere;	41 g

Dimethyl phosphite (868-85-9) + acetylacetone (123-54-6) → dimethyl (2-oxopropyl)phosphonate (4202-14-6)

Conditions	Yield
With dipotassium peroxodisulfate; silver(I) acetate In water; N,N-dimethyl-formamide at 85℃; for 24h; Inert atmosphere; Schlenk technique; chemoselective reaction;	72%

chloroacetone (78-95-5) → dimethyl (2-oxopropyl)phosphonate (4202-14-6)

Conditions	Yield
With potassium iodide; phosphorous acid trimethyl ester In acetone; acetonitrile	71%

Dimethyl phosphite (868-85-9) + acetone (67-64-1) → dimethyl (2-oxopropyl)phosphonate (4202-14-6)

Conditions	Yield
With dipotassium peroxodisulfate; silver(I) acetate In water at 85℃; Inert atmosphere; Schlenk technique; chemoselective reaction;	60%

acetic acid methyl ester (79-20-9) + dimethyl methane phosphonate (756-79-6) → dimethyl (2-oxopropyl)phosphonate (4202-14-6)

Conditions	Yield
Stage #1: dimethyl methane phosphonate With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: acetic acid methyl ester In tetrahydrofuran; hexane at -78 - 0℃; Further stages.;	56%
Stage #1: dimethyl methane phosphonate With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: acetic acid methyl ester In tetrahydrofuran; hexane at -78 - 0℃;	55%
Stage #1: dimethyl methane phosphonate With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 3h; Stage #2: acetic acid methyl ester In tetrahydrofuran; hexane at -78 - 0℃;
With lithium diisopropyl amide In tetrahydrofuran at -5 - 0℃; Inert atmosphere;

ethyl acetate (141-78-6) + dimethyl methane phosphonate (756-79-6) → dimethyl (2-oxopropyl)phosphonate (4202-14-6)

Conditions	Yield
Stage #1: dimethyl methane phosphonate With n-butyllithium In hexane; toluene at -80℃; for 0.166667h; Inert atmosphere; Stage #2: ethyl acetate In hexane; toluene at -80℃; for 1h; Inert atmosphere;	50%
With n-butyllithium 1.) THF, -78 deg C, 15 min, 2.) THF, -78 deg C, 30 min; Multistep reaction;

4-chlorophenyl acetate (876-27-7) + dimethyl (2-hydroxypropyl)phosphonate (54731-75-8) → dimethyl (2-oxopropyl)phosphonate (4202-14-6) + (R)-dimethyl 2-acetyloxypropylphosphonate

Conditions	Yield
With (hydroxy)tetraphenylcyclopentadienyl-based ruthenium; Candida antarctica lipase B (Novozym-435) In toluene at 70℃; for 24h;	A 16% B 62 % Spectr.

chloroacetone (78-95-5) + phosphorous acid trimethyl ester (121-45-9) → phosphoric acid isopropenyl ester dimethyl ester (4185-82-4) + dimethyl (2-oxopropyl)phosphonate (4202-14-6)

acetyl chloride (75-36-5) + dimethyl methane phosphonate (756-79-6) → dimethyl (2-oxopropyl)phosphonate (4202-14-6)

Conditions	Yield
(i) nBuLi, hexane, THF, (ii) Cu2I2, (iii) /BRN= 605303/, Et2O; Multistep reaction;

1-bromoacetone (598-31-2) + phosphorous acid trimethyl ester (121-45-9) → dimethyl (2-oxopropyl)phosphonate (4202-14-6)

Conditions	Yield
In methanol Heating;
at 120℃; for 1.5h;

methanol (67-56-1) + dimethyl 1-(1-diazo-2-oxopropyl)phosphonate (90965-06-3) → dimethyl (2-oxopropyl)phosphonate (4202-14-6) + trimethyl 2-phosphonopropionate (26530-60-9)

Conditions	Yield
at 0℃; Irradiation;	A 12.3 % Chromat. B 87.5 % Chromat.

dimethyl 1-(1-diazo-2-oxopropyl)phosphonate (90965-06-3) → dimethyl (2-oxopropyl)phosphonate (4202-14-6) + trimethyl 2-phosphonopropionate (26530-60-9)

Conditions	Yield
In methanol at 0℃; Irradiation;	A 12.3 % Chromat. B 87.5 % Chromat.

1,2-propenephosphonic acid methyl ester (56504-60-0) → dimethyl (2-oxopropyl)phosphonate (4202-14-6)

Conditions	Yield
With water; oxygen; p-benzoquinone; lithium chloride; palladium dichloride at 65℃; for 26h; Yield given;

methyl 2-dimethoxyphosphoryl-3-oxobutyrate (58393-50-3) → dimethyl (2-oxopropyl)phosphonate (4202-14-6)

Conditions	Yield
With water for 2.5h; Heating; Yield given;

chloroacetone (78-95-5) + phosphorous acid trimethyl ester (121-45-9) → dimethyl (2-oxopropyl)phosphonate (4202-14-6) + phosphonic acid isopropenyl ester-dimethyl ester

1-bromoacetone (598-31-2) + phosphorous acid trimethyl ester (121-45-9) → dimethyl (2-oxopropyl)phosphonate (4202-14-6) + phosphonic acid isopropenyl ester-dimethyl ester

allylphosphonic acid dimethyl ester (757-54-0) → dimethyl (2-oxopropyl)phosphonate (4202-14-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: KOtBu 2: LiCl, p-benzoquinone, O2, H2O / PdCl2 / 26 h / 65 °C View Scheme

dimethyl (2-oxopropyl)phosphonate (4202-14-6) → dimethyl 1-(1-diazo-2-oxopropyl)phosphonate (90965-06-3)

Conditions	Yield
Stage #1: dimethyl (2-oxopropyl)phosphonate With sodium hydride In tetrahydrofuran; mineral oil; benzene at 20℃; for 1h; Inert atmosphere; Cooling with ice; Stage #2: With 4-toluenesulfonyl azide In tetrahydrofuran; mineral oil; benzene at 20℃; Inert atmosphere;	100%
Stage #1: dimethyl (2-oxopropyl)phosphonate With sodium hydride In tetrahydrofuran; mineral oil; benzene at 20℃; for 1h; Inert atmosphere; Cooling with ice; Stage #2: With 4-toluenesulfonyl azide In tetrahydrofuran; mineral oil; benzene at 20℃; Inert atmosphere;	99%
With 4-toluenesulfonyl azide In tetrahydrofuran; benzene at 0 - 20℃; for 2h; Substitution;	98%

dimethyl (2-oxopropyl)phosphonate (4202-14-6) + 3,4-dichlorobenzaldehyde (6287-38-3) → (E)-4-(3,4-dichlorophenyl)but-3-en-2-one (55420-70-7)

Conditions	Yield
With potassium carbonate In water at 5℃; for 0.25h;	100%

dimethyl (2-oxopropyl)phosphonate (4202-14-6) → Dimethyl-1,1-difluoro-2-oxypropyl phosphonate

Conditions	Yield
Stage #1: dimethyl (2-oxopropyl)phosphonate With potassium tert-butylate In tert-butyl alcohol at 20℃; for 0.5h; Stage #2: With acetyl hypofluorite In tert-butyl alcohol at 20℃;	100%

dimethyl (2-oxopropyl)phosphonate (4202-14-6) → (R)-2-hydroxy-1-dimethoxyphosphorylpropane

Conditions	Yield
With RuCl2((R)-binap)(dmf)n; hydrogen In methanol at 25℃; under 3040 Torr; for 72h;	99%
Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / Inert atmosphere 1.2: 16 h / Inert atmosphere 2.1: BF4(1-)*C50H59IrO3P2(1+); hydrogen / dichloromethane / 24 h / 25 °C / 3040.2 Torr 3.1: sodium carbonate / methanol / 16 h View Scheme
Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / Inert atmosphere 1.2: 16 h / Inert atmosphere 2.1: BF4(1-)*C44H63IrO3P2(2+); hydrogen / dichloromethane / 24 h / 25 °C / 3040.2 Torr 3.1: sodium carbonate / methanol / 16 h View Scheme

Martins sulfurane (32133-82-7) + dimethyl (2-oxopropyl)phosphonate (4202-14-6) → dimethyl 2-(diphenylsulfuranylidene)-2-oxopropylphosphonate (1433220-51-9)

Conditions	Yield
In diethyl ether at 25℃; for 0.5h; Schlenk technique; Inert atmosphere;	99%

dimethyl (2-oxopropyl)phosphonate (4202-14-6) + 4-nitrobenzaldehdye (555-16-8) → (4-Nitrophenyl)acetylene (937-31-5)

Conditions	Yield
With potassium carbonate In methanol at 20℃; for 18h; Seyferth-Gilbert Homologation; Inert atmosphere;	99%

dimethyl (2-oxopropyl)phosphonate (4202-14-6) + C32H42F2N2O6Si2 → C33H42F2N2O5Si2

Conditions	Yield
Stage #1: dimethyl (2-oxopropyl)phosphonate With 4-toluenesulfonyl azide; potassium carbonate In acetonitrile at 25℃; for 2h; Inert atmosphere; Stage #2: C32H42F2N2O6Si2 In methanol; acetonitrile at 25℃; for 12h; Inert atmosphere;	98.2%
Stage #1: dimethyl (2-oxopropyl)phosphonate With 4-toluenesulfonyl azide; potassium carbonate In acetonitrile at 25℃; for 2h; Inert atmosphere; Stage #2: C32H42F2N2O6Si2 In methanol at 25℃; for 12h; Inert atmosphere;	98.2%
Stage #1: dimethyl (2-oxopropyl)phosphonate With 4-toluenesulfonyl azide; potassium carbonate In acetonitrile at 25℃; for 2h; Inert atmosphere; Stage #2: C32H42F2N2O6Si2 In methanol; acetonitrile at 25℃; for 12h;	98.2%

4-toluenesulfonyl azide (941-55-9) + dimethyl (2-oxopropyl)phosphonate (4202-14-6) → dimethyl (1-diazo-2-oxopropyl)phosphonate

Conditions	Yield
Stage #1: dimethyl (2-oxopropyl)phosphonate With sodium hydride In tetrahydrofuran; benzene at 0℃; for 1h; Stage #2: 4-toluenesulfonyl azide In tetrahydrofuran; benzene at 20℃; for 2h;	98%

dimethyl (2-oxopropyl)phosphonate (4202-14-6) + C28H30N2O5 → benzyl ((S)-1-(((S)-1-(dimethoxyphosphoryl)-2-oxo-5-phenylpentan-3-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate

Conditions	Yield
Stage #1: dimethyl (2-oxopropyl)phosphonate With n-butyllithium In tetrahydrofuran; hexane at -70℃; for 0.25h; Inert atmosphere; Stage #2: C28H30N2O5 In tetrahydrofuran; hexane at -70℃; for 2h; Inert atmosphere;	98%

dimethyl (2-oxopropyl)phosphonate (4202-14-6) + 2-N,N-Dibenzylaminoacetaldehyde (106889-84-3) → (E)-5-(dibenzylamino)pent-3-en-2-one

Conditions	Yield
Stage #1: dimethyl (2-oxopropyl)phosphonate With lithium bromide In tetrahydrofuran at 20℃; for 0.0833333h; Horner-Wadsworth-Emmons Olefination; Inert atmosphere; Stage #2: With triethylamine In tetrahydrofuran for 0.166667h; Inert atmosphere; Stage #3: 2-N,N-Dibenzylaminoacetaldehyde In tetrahydrofuran for 0.75h; Inert atmosphere;	98%

dimethyl (2-oxopropyl)phosphonate (4202-14-6) + 2,3-isopropylidene-glyceraldehyde (15186-48-8) → (3E)-4-[(4S)-2,2-dimethyl(1,3-dioxolan-4-yl)]but-3-en-2-one (64482-41-3)

Conditions	Yield
With potassium carbonate In tetrahydrofuran; water at 0℃; for 1h;	97%
With sodium hydride 1.) THF 1.5h at room temp.; 2.) 2 h from 0 degC to 5 degC; Yield given. Multistep reaction;
With potassium carbonate at 0℃; for 3h; Yield given;
With potassium carbonate

dimethyl (2-oxopropyl)phosphonate (4202-14-6) + (S)-2-[(R)-3-(tert-Butyl-dimethyl-silanyloxy)-1-methyl-propyl]-2,5-dimethyl-hex-4-enal (226065-51-6) → (E)-(S)-5-[(R)-3-(tert-Butyl-dimethyl-silanyloxy)-1-methyl-propyl]-5,8-dimethyl-nona-3,7-dien-2-one (226065-52-7)

Conditions	Yield
With n-butyllithium In toluene Heating;	97%

4-methyl-N-[(2S)-3-methyl-1-oxobutan-2-yl]benzenesulfonamide (887113-19-1) + dimethyl (2-oxopropyl)phosphonate (4202-14-6) → (S,E)-4-methyl-N-(2-methyl-6-oxohept-4-en-3-yl)benzenesulfonamide

Conditions	Yield
Stage #1: dimethyl (2-oxopropyl)phosphonate With N-ethyl-N,N-diisopropylamine; lithium chloride In acetonitrile at 0℃; for 0.333333h; Stage #2: 4-methyl-N-[(2S)-3-methyl-1-oxobutan-2-yl]benzenesulfonamide In acetonitrile at 20℃; for 2h;	97%

trimethylsilyl cyanide (7677-24-9) + dimethyl (2-oxopropyl)phosphonate (4202-14-6) → (2-Cyano-2-methyl-2-trimethylsilanyloxy-ethyl)-phosphonic acid dimethyl ester (88631-43-0)

Conditions	Yield
With potassium cyanide; 18-crown-6 ether In dichloromethane for 2h;	96%

dimethyl (2-oxopropyl)phosphonate (4202-14-6) + 4-(Tetrahydro-pyran-2-yloxy)-non-5-ynal (139338-88-8) → (E)-7-(Tetrahydro-pyran-2-yloxy)-dodec-3-en-8-yn-2-one (139338-89-9)

Conditions	Yield
With sodium hydride	96%
With sodium hydride	92%

(2S,3R,4R)-2,3-bis-(p-methoxybenzyloxy)-4-[5-(R)-(p-methoxybenzyloxy)-2,2,6-(6R)-trimethyl-1,3-dioxan-4-(R)-yl]-pentanal (862509-80-6) + dimethyl (2-oxopropyl)phosphonate (4202-14-6) → (3E,5R,6R,7R)-5,6-bis-(p-methoxybenzyloxy)-7-[5-(R)-(p-methoxybenzyloxy)-2,2,6-(6R)-trimethyl-1,3-dioxan-4-(R)-yl]-oct-3-en-2-one (392692-56-7)

Conditions	Yield
Stage #1: dimethyl (2-oxopropyl)phosphonate With barium dihydroxide In tetrahydrofuran at 20℃; for 0.5h; Stage #2: (2S,3R,4R)-2,3-bis-(p-methoxybenzyloxy)-4-[5-(R)-(p-methoxybenzyloxy)-2,2,6-(6R)-trimethyl-1,3-dioxan-4-(R)-yl]-pentanal In tetrahydrofuran; water at 20℃; for 4h; Horner-Wadsworth-Emmons chain extension;	96%

dimethyl (2-oxopropyl)phosphonate (4202-14-6) → dimethyl (S)-(2-hydroxypropyl)phosphonate

Conditions	Yield
With C48H44ClO4P2Ru(1+)*Cl(1-); hydrogen In methanol at 50℃; under 7500.75 Torr; for 19h; Inert atmosphere; enantioselective reaction;	95.3%

dimethyl (2-oxopropyl)phosphonate (4202-14-6) + ethyl (E)-3-((E)-carbamoyldiazenyl)but-2-enoate (146000-77-3) → 4-(Dimethoxy-phosphoryl)-2,5-dimethyl-1-ureido-1H-pyrrole-3-carboxylic acid ethyl ester

Conditions	Yield
With sodium hydride In tetrahydrofuran for 2h; Ambient temperature;	95%

dimethyl (2-oxopropyl)phosphonate (4202-14-6) + cyclohexanone (108-94-1) → 1-cyclohexylidene-2-propanone (874-68-0)

Conditions	Yield
With potassium hydroxide In ethanol; water at 20℃; for 28h; Wittig-Horner reaction;	95%

Tetrahydro-4H-pyran-4-one (29943-42-8) + dimethyl (2-oxopropyl)phosphonate (4202-14-6) → 1-(dihydro-2H-pyran-4(3H)-ylidene)propan-2-one (912441-79-3)

Conditions	Yield
With potassium hydroxide In ethanol; water at 0 - 20℃; for 5h; Horner-Wadsworth-Emmons Olefination; Inert atmosphere;	95%
With potassium hydroxide In ethanol; water at 20℃; for 5h;	82%
With potassium hydroxide In ethanol at 0 - 20℃;
With potassium hydroxide In ethanol; water at 0 - 20℃;
With potassium hydroxide In ethanol; water at 0℃; for 4h;

dimethyl (2-oxopropyl)phosphonate (4202-14-6) + 3-trifluoromethylphenylazide (22001-17-8) → C12H13F3N3O3P

Conditions	Yield
With tetramethylguanidinium acetate at 50℃; for 1.5h; Ionic liquid;	95%

dimethyl (2-oxopropyl)phosphonate (4202-14-6) + 1-azido-4-bromobenzene (2101-88-4) → C11H13BrN3O3P

Conditions	Yield
With C5H14N3(1+)*HO(1-) at 50℃; for 2h; Ionic liquid;	95%

dimethyl (2-oxopropyl)phosphonate (4202-14-6) + orthoformic acid triethyl ester (122-51-0) → dimethyl 2-ethoxypropenylphosphonate (73542-47-9)

Conditions	Yield
With iron(III) chloride for 72h; Ambient temperature;	94%
With iron(III) chloride
With iron(III) chloride Substitution;

dimethyl (2-oxopropyl)phosphonate (4202-14-6) + (R)-3-((tert-butyldimethylsilyl)oxy)-1-iodobutane (109613-36-7) → dimethyl (6R)-(6-[(tert-butyldimethylsilyl)oxy]-2-oxoheptyl)phosphonate (121484-92-2)

Conditions	Yield
With n-butyllithium; sodium hydride In tetrahydrofuran at 0℃; for 30h;	94%

4-[(2R,6R)-4-Methylene-6-(2-oxo-ethyl)-tetrahydro-pyran-2-yl]-but-2-ynoic acid methyl ester (799852-58-7) + dimethyl (2-oxopropyl)phosphonate (4202-14-6) → 4-[(2R,6S)-4-Methylene-6-((E)-4-oxo-pent-2-enyl)-tetrahydro-pyran-2-yl]-but-2-ynoic acid methyl ester (799852-60-1)

Conditions	Yield
Stage #1: dimethyl (2-oxopropyl)phosphonate With barium dihydroxide In tetrahydrofuran for 0.5h; Stage #2: 4-[(2R,6R)-4-Methylene-6-(2-oxo-ethyl)-tetrahydro-pyran-2-yl]-but-2-ynoic acid methyl ester In tetrahydrofuran; water for 1.75h; Horner-Wadsworth-Emmons reaction;	94%

ethyl 2-amino-4-benzyl-5-phenylthiophene-3-carboxylate + dimethyl (2-oxopropyl)phosphonate (4202-14-6) → C23H22NO4PS

Conditions	Yield
With toluene-4-sulfonic acid In toluene for 24h; Reflux; Dean-Stark;	94%

dimethyl (2-oxopropyl)phosphonate (4202-14-6) + tert-butyl 5-formyl-2,2-dimethyl-1,3-dioxan-5-ylcarbamate (364631-73-2) → 5-ethynyl-2,2-dimethyl-[1,3]dioxan-(N-tert-butyloxycarbonyl)-5-ylamine (364631-74-3)

Conditions	Yield
Stage #1: dimethyl (2-oxopropyl)phosphonate With 4-toluenesulfonyl azide; potassium carbonate In toluene; acetonitrile at 20℃; for 2.5h; Stage #2: tert-butyl 5-formyl-2,2-dimethyl-1,3-dioxan-5-ylcarbamate In methanol; toluene; acetonitrile for 1.5h;	93.4%
Stage #1: dimethyl (2-oxopropyl)phosphonate With 4-toluenesulfonyl azide; potassium carbonate In acetonitrile at 20℃; for 2h; Stage #2: tert-butyl 5-formyl-2,2-dimethyl-1,3-dioxan-5-ylcarbamate In methanol; acetonitrile at 20℃; for 8h;	84%

tert-butyl 3-formylazetidine-1-carboxylate (177947-96-5) + dimethyl (2-oxopropyl)phosphonate (4202-14-6) → tert-butyl 3-ethynylazetidine-1-carboxylate (287193-01-5)

Conditions	Yield
Stage #1: dimethyl (2-oxopropyl)phosphonate With sodium azide; caesium carbonate; methanesulfonyl chloride In acetonitrile at 0 - 20℃; for 3h; Stage #2: tert-butyl 3-formylazetidine-1-carboxylate With caesium carbonate In methanol; acetonitrile at 0℃;	93%

dimethyl (2-oxopropyl)phosphonate (4202-14-6) + methyl (E)-4,4-dimethyl-6-oxo-2-hexenoate (132298-32-9) → methyl (E,E)-4,4-dimethyl-8-oxo-2,6-nonadienoate (72808-49-2)

Conditions	Yield
Stage #1: dimethyl (2-oxopropyl)phosphonate With sodium hydride In tetrahydrofuran at 0℃; for 1h; Stage #2: methyl (E)-4,4-dimethyl-6-oxo-2-hexenoate In tetrahydrofuran Horner-Wadsworth-Emmons olefination; Heating; Further stages.;	92%

dimethyl (2-oxopropyl)phosphonate (4202-14-6) + C15H18O5 (1108588-18-6) → C18H22O5 (1108588-22-2)

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran at 0℃; Horner-Emmons olefination;	92%

Upstream product

• 78-95-5 chloroacetone 
• 121-45-9 phosphorous acid trimethyl ester 
• 598-31-2 1-bromoacetone 
• 876-27-7 4-chlorophenyl acetate 
• 54731-75-8 dimethyl (2-hydroxypropyl)phosphonate 
• 868-85-9 Dimethyl phosphite 
• 123-54-6 acetylacetone 
• 67-64-1 acetone 
• 757-54-0 allylphosphonic acid dimethyl ester 
• 79-20-9 acetic acid methyl ester 
• 756-79-6 dimethyl methane phosphonate 
• 141-78-6 ethyl acetate 
• 58393-50-3 methyl 2-dimethoxyphosphoryl-3-oxobutyrate 
• 56504-60-0 1,2-propenephosphonic acid methyl ester 

Downstream Products

• 95242-44-7 {1-[1-(3-Nitro-phenyl)-meth-(E)-ylidene]-2-oxo-propyl}-phosphonic acid dimethyl ester 
• 14309-57-0 Non-3-en-2-on 
• 5166-53-0 5-methyl-3-hexene-2-one 
• 107346-97-4 {1-[1-(2-Nitro-phenyl)-meth-(Z)-ylidene]-2-oxo-propyl}-phosphonic acid dimethyl ester 
• 163812-44-0 4-benzyloxy-1-dimethylphosphinoylbutan-2-one 
• 169129-44-6 (E)-6-[N-benzyl-N-(tert-butoxycarbonyl)amino]-3-hexen-2-one 
• 172603-21-3 (2S,3R,4R,5R,6R,5'S,6'R,7'R,8'R)-(3'E)-9'-<3,4-Bis(benzyloxy)-5-ethyl-tetrahydro-2-methoxy-2H-pyran-6-yl>-6'-methoxy-8'-<(methoxymethyl)oxy>-5',7'-dimethyl-3'-nonen-2'-one 
• 195299-18-4 (E)-5-((3R,5R,7aS)-3-Phenyl-hexahydro-pyrrolo[2,1-b]oxazol-5-yl)-pent-3-en-2-one 
• 194934-61-7 (E)-(5R,6R,7R)-7-((4R,5R,6R)-5-Benzyloxy-2,2,6-trimethyl-[1,3]dioxan-4-yl)-5,6-bis-(2-trimethylsilanyl-ethoxymethoxy)-oct-3-en-2-one 
• 248602-63-3 (E)-phenyl-2-dimethylphosphono-3-acetic acid acid ethyl ester 
• 248602-65-5 (E)-3-Dimethoxyphsphoryl-4-(4-methoxyphenyl)but-3-en-2-one 
• 107346-98-5 (E)-3-Dimethoxyphosphoryl-4-(2-nitrophenyl)but-3-en-2-one 
• 269715-87-9 [(E)-(1S,2R,3S)-3-(tert-Butyl-dimethyl-silanyloxy)-1-(tert-butyl-dimethyl-silanyloxymethyl)-2-methyl-7-oxo-oct-5-enyl]-carbamic acid benzyl ester 
• 326496-56-4 (E)-4-[4-(4,5-Dimethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-but-3-en-2-one 

Relevant articles and documents

Organocatalytic enantioselective 1,3-dipolar cycloadditions between seyferth-gilbert reagent and isatylidene malononitriles: Synthesis of chiral spiro-phosphonylpyrazoline-oxindoles

A new method has been developed for the catalytic enantioselective 1,3-dipolar cycloaddition of the Seyferth-Gilbert reagent (SGR) to isatylidene malononitriles using a cinchona alkaloid derivative as a catalyst. This method allowed for the synthesis of a series of chiral spiro-phosphonylpyrazoline-oxindoles in good yields with excellent enantioselectivities. The synthetic utility of this method was further demonstrated by its use in a three-component domino reaction involving isatin, malononitrile, and SGR based on sequential Knoevenagel condensation and 1,3-dipolar cycloaddition reactions.

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Alkyl phosphonate preparing method

The invention provides an alkyl phosphonate preparing method. The method comprises: performing an Arbuzov reaction on compound A and compound B in a continuous reaction apparatus, and continuously discharging the product obtained from the reaction from the continuous reaction apparatus during the reaction procedure, to obtain alkyl phosphonate. The reaction temperature in the reaction procedure is T1; either of compound A and compound B having a lower boiling point has a boiling point at a standard atmosphere pressure to be T2; T1 is higher than T2 by 10-40 DEG C; and the reaction pressure in the reaction procedure is 0.5-2.0 MPa. The preparing method in the invention may use halohydrocarbon having large steric hindrance and lower polarizability of carbon-halogen bond as compound A, thereby effectively expanding a selection range of substrate, and correspondingly expanding the types of alkyl phosphonate prepared by using the Arbuzov reaction.

REMOVAL OF SENESCENCE-ASSOCIATED MACROPHAGES

In various aspects and embodiments provided are compounds, compositions and methods relating to aging, senescent cells (SCs) and/or senescence associate macrophages (SAMs). In certain aspects and embodiments provided are compounds and compositions that selectively kill or reprogram senescent cells (SCs) and or senescence associate macrophages (SAMs) and associated methods. In some embodiments, the compounds compositions and methods treat or reverse aging and/or age-related diseases.