Potassium di-tert-butyl phosphate Chemical Properties

Melting point:

247-252°C

storage temp. 

2-8°C

form 

Powder

color 

white

InChI

InChI=1S/C8H19O4P.K/c1-7(2,3)11-13(9,10)12-8(4,5)6;/h1-6H3,(H,9,10);/q;+1/p-1

InChIKey

ZSWXMOQFFWMZQH-UHFFFAOYSA-M

SMILES

[K+].P([O-])(OC(C)(C)C)(OC(C)(C)C)=O

CAS DataBase Reference

33494-80-3

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26

WGK Germany 

3

TSCA 

No

HS Code 

2919900090

Potassium di-tert-butyl phosphate Usage And Synthesis

Uses

Di-tert-butylphosphate Potassium Salt is a catalyst used in organic synthesis. Also used in the preparation of HIV attachment inhibitor BMS-663068.

Application

Utilized as an intermediate to prepare N-phosphonooxymethyl prodrugs, which increase bioavailability, and to prepare Nasicon-type phosphates (i.e., KTi₂(PO₄)₃) used in fast ion conductors with low thermal expansion ceramics.appl

Preparation

Potassium di-tert-butyl phosphate synthesis: Di-tert-butyl phosphite (40.36 mmol) was combined with potassium bicarbonate (24.22 mmol) in 35 ml of water. The solution was stirred in an ice bath and potassium permanganate (28.25 mmole) was added in three equal portions over a period of one hour. The reaction was then allowed to continue for another half hour at room temperature. Decolorizing carbon (600 mg) was then incorporated as the reaction was heated to 60 °C for 15 min. The reaction was then vacuum filtered to remove solid magnesium dioxide. The solid was washed several times with water. The filtrate was then combined with one gram of decolorizing carbon and heated at 60°C for another twenty minutes. The solution was filtered again to give a colorless solution, which was then evaporated in vacuo to give the crude potassium di-tert-butyl phosphate salt.

Flammability and Explosibility

Non flammable

reaction suitability

reaction type: Buchwald-Hartwig Cross Coupling Reaction
reaction type: Heck Reaction
reaction type: Hiyama Coupling
reaction type: Negishi Coupling
reaction type: Sonogashira Coupling
reaction type: Stille Coupling
reaction type: Suzuki-Miyaura Coupling
reagent type: ligand

Synthesis

General procedure for the synthesis of the potassium salt of di-tert-butyl phosphate from di-tert-butyl phosphite: 1. di-tert-butyl phosphite (40.36 mmol) was mixed with potassium bicarbonate (24.22 mmol) in 35 mL of water. 2. the mixed solution was placed in an ice bath with stirring and potassium permanganate (28.25 mmol) was added in three equal portions over a period of 1 hour. 3. The reaction continues to be stirred at room temperature for 30 minutes. 4. Decolorized carbon (600 mg) was added and the reaction mixture was heated to 60 °C and maintained for 15 min. 5. The reaction mixture was vacuum filtered to remove the solid manganese dioxide. 6. 6. The solid was washed several times with water. 7. The filtrate was combined with 1 g of decolorized carbon and heated at 60 °C for 20 min. 8. The filtrate was filtered again to give a colorless solution followed by vacuum evaporation to give the crude di-tert-butyl potassium phosphate salt. 9. The crude potassium salt of di-tert-butyl phosphate (5 g, 20.14 mmol) was dissolved in methanol (15 g). 10. A slight excess of concentrated hydrochloric acid was slowly added to the solution at 0 °C while maintaining effective stirring. 11. After addition of hydrochloric acid, potassium chloride precipitated, filtered and washed with methanol. 12. An equimolar amount of tetramethylammonium hydroxide (3.65 g, 20.14 mmol) was added to the mother liquor while the reaction was kept cool and effectively stirred in a salt/ice bath. 13. The resulting clarified solution was placed under reduced pressure to give the crude product. 14. Tetramethylammonium di-tert-butyl phosphate was dissolved in refluxed dimethoxyethane, chloroiodomethane (4.3 g, 24.16 mmol) was added and stirred for 1-2 hours. 15. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure to give a solution of dimethoxyethane. 16. The chloromethyl di-tert-butyl phosphate (12-16%) from this solution was used directly in the next step in the synthesis of 4-(5-(2-(2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethylpropanamido)-4-(o-tolyl)pyridin-2-yl)-1-methyl-1-((phosphonoyloxy)methyl)piperazin-1-ium without further purification (60% yield). Characterization data: 1H NMR (CD3OD, 300 MHz) δ 1.51 (s, 12H), 5.63 (d, 2H, J = 14.8 Hz). 31P NMR (CD3OD, 300 MHz) δ -11.3 (s, 1P).

References

[1] Patent: EP1051181, 2004, B1. Location in patent: Page/Page column 15
[2] Patent: US8426450, 2013, B1. Location in patent: Page/Page column 32; 33
[3] Patent: US9403772, 2016, B2. Location in patent: Page/Page column 37
[4] Patent: JP2015/17121, 2015, A. Location in patent: Paragraph 0179-0181

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