References
- McMurry , T. J. PCT Publication WO 96/23526
- Sajiki , H. 1996 . Synth. Comm. , 26 ( 13 ) : 2511
- Deutsch , J. German Patent . #3806795 . 1988 .
- Deutsch , J. European Patent . #305320 . 1988 .
- Deutsch , J. PCT Publication WO 88/08422
- Compound 2 was isolated as a solution in heptane and used directly in a phosphorylation sequence. The phosphorylation chemistry will be published elsewhere
- McNulty , J. and Still , I. W. J. 1992 . Synth. Commun. , 22 ( 7 ) : 979 Toluene provides a suitable azeotrope with ethylenediamine under the solvent ratios described in the experimental section
- This operation removed the remaining ethylenediamine and furnished a filterable solid
- No change in purity was observed for 3a over a period of one year at room temperature, whereas 3b decomposes at room temperature overnight
- The production of diethyl ether from BF3-etherate creates a safety hazard due to its flash point (-40 °C)
- The severe exotherm was identified using Differential Scanning Calorimetry (DSC)
- Impurity 6. if carried on in >2.0% quantities, contaminated the compound 2 solution, prohibiting acceptable drug substance based on purity (see reference 3)
- No severe exotherms were identified using Differential Scanning Calorimetry (DSC)
- When the aqueous layer was more acidic than pH=4.5 tert-butyl ester hydrolysis was observed
- The typical weight range of the crude 2 solution was 150–250 g. The purity based on a standard (purified 2, weight %) depends on the quantity of heptane. Compound 2 as a solution in this range provided similar results in the phosphorylation sequence (see reference 3)