80141-24-8

Upstream product

• 10416-59-8 N,O-bis-(trimethylsilyl)-acetamide 
• 4712-55-4 diphenyl hydrogen phosphite 
• 25561-30-2 N,O-Bis(trimethylsilyl)trifluoroacetamide 
• 75-77-4 chloro-trimethyl-silane 

Downstream Products

• 146399-35-1 2-Phenoxy-2-oxo-(3,5-di-tert-butyl)benzo-1,3,2-dioxaphospholin 
• 147608-44-4 <(1-Trimethylsiloxy-2,2-diphenyl)ethenyl>phosphonsaeure-diphenylester 
• 403-65-6 diphenyl phosphorofluoridate 
• 146399-45-3 Phosphorsaeure-diphenyl-9-(10-trimethylsiloxy)-phenanthrylester 
• 14156-07-1 O,O′-diphenyl S-hydrogen phosphorothioate 
• 622867-98-5 diphenyl benzyloxymethylphosphonate 
• 1412911-86-4 Benzyloxymethylphosphonic Acid, Monophenyl Ester, Monosodium Salt 
• 1412911-87-5 C₁₉H₂₄NO₅P 
• 52364-31-5 diphenyl hydroxymethylphosphonate 

Relevant academic research and scientific papers

On the sulfurization of h-phosphonate diesters and phosphite triesters using elemental sulfur

Sulfurization of tetracoordinate and tricoordinate P(III) derivatives, namely, H-phosphonate diesters, H-phosphonothioate diesters, and phosphite triesters with elemental sulfur under various experimental conditions, was investigated.

Synthesis of Rovafovir Etalafenamide (Part III): Evolution of the Synthetic Process to the Phosphonamidate Fragment

Phosphonamidate 1 is a key fragment in the assembly of rovafovir etalafenamide, a novel nucleotide reverse transcriptase inhibitor under development at Gilead Sciences for the treatment of HIV infection. An early manufacturing route, relying on simulated moving bed (SMB) chromatography for the separation of phosphorus diastereomers, was executed on scale to produce multiple batches of 1. However, developing alternative synthetic conditions became desirable in consideration of the high production cost, long lead time, and high process mass intensity (PMI) associated with SMB. Several strategies to improve these factors are described herein, including epimerization and recycling of the undesired (R)-phosphorus diastereomer, design of stereoselective approaches to establish the desired (S)-configuration at phosphorus, and identification of conditions or derivatives to allow for selective crystallization. Ultimately, a second-generation route to 1 was developed and demonstrated on scale. The new route achieves the separation of phosphorus diastereomers by means of selective crystallization, does not require SMB, and offers lower PMI, cost, and lead time.

Arylation of Axially Chiral Phosphorothioate Salts by Dinuclear PdI Catalysis

S-aryl phosphorothioates are privileged motifs in pharmaceuticals, agrochemicals, and catalysts; yet, the challenge of devising a straightforward synthetic route to enantioenriched S-aryl phosphorothioates has remained unsolved to date. We demonstrate herein the first direct C?SP(=O)(OR′)(OR′′) coupling of diverse and chiral phosphorothioate salts with aryl iodides, enabled by an air- and moisture-stable PdI dimer. Our mechanistic and computational data suggest distinct dinuclear PdI catalysis to be operative, which allows for operationally simple couplings with broad scope and full retention of stereochemistry.

Photoinduced Cyclization of (o-Alkylbenzoyl)phosphonates to Benzocyclobutenols

(o-Alkylbenzoyl)phosphonates readily cyclize to highly strained benzocyclobutenols simply upon irradiation with UV light. The remarkable efficiency is ascribed to the electron-accepting character of the phosphonate substituent, which facilitates thermal ring closing of the o-quinodimethane intermediate and suppresses reversion to the starting carbonyl compound.

PROCESSES AND INTERMEDIATES FOR PREPARING ANTI-HIV AGENTS

The invention provides synthetic processes and synthetic intermediates that can be used to prepare compounds having useful anti-HIV properties.