1645-58-5

Upstream product

• 64-17-5 ethanol 
• 1993-81-3 ethyl-1,3-dibromo-3,3-difluoropropyl ether 
• 75-61-6 dibromodifluoromethane 
• 109-92-2 ethyl vinyl ether 

Downstream Products

• 407-35-2 ethyl β,β-difluoroacrylate 
• 105304-62-9 ethyl (2Z)-3-fluoro-3-phenylprop-2-enoate 
• 70260-27-4 ethyl (E)-3-phenyl-3-fluoro-2-propenoate 
• 108221-68-7 ethyl 2-bromo-3,3,3-trifluoropropanoate 
• 352-23-8 ethyl 3,3,3-trifluoropropanoate 

Relevant academic research and scientific papers

Diethyl 3-bromo-3,3-difluoropropyl acetal: Preparation and SnCl4-promoted cross-coupling reaction with trimethylsilyl enol ethers

The radical addition of dibromodifluoromethane to ethyl vinyl ether in ethanol under Na2S2O4 initiation affords diethyl 3-bromo-3,3-difluoropropyl acetal (1) in high yield. SnCl4-promoted cross-coupling reaction of 1 with trimethylsilyl enol ethers (2) yield γ-bromodifluoromethyl-β-ethoxy ketones (3).

HOT MELT EXTRUDED SOLID DISPERSIONS CONTAINING A BCL2 INHIBITOR

A pro-apoptotic solid dispersion comprises, a Bcl -2 family protein inhibitory compound of Formula A as defined herein, dispersed in a solid matrix that comprises (a) a pharmaceutically acceptable water-soluble polymeric carrier, and (b) a pharmaceutically acceptable surfactant. A process for preparing such a solid dispersion comprises subjecting to elevated temperature the compound of Formula A, the water-soluble polymeric carrier, and the surfactant to provide an extrudable semi-solid mixture; extruding the semi-solid mixture; and cooling the resulting extrudate to provide a solid matrix comprising the polymeric carrier, and the surfactant and having the compound dispersed in essentially non-crystalline form therein. The solid dispersion is suitable for oral administration to a subject in need thereof for treatment of a disease characterized by overexpression of one or more anti-apoptotic Bcl -2 family proteins, for example cancer or an immune or autoimmune disease.

CONDENSED HETEROCYCLES AS BCL-2 INHIBITORS

The disclosure includes compounds of Formula (A) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11, h, j, m, n, k, v, s, g, V, W, L, Z1 Q1, Q2, Q3, Q4, Q5, Q6, and Q7, are defined herein. Also disclosed is a method for treating a neoplastic disease, an autoimmune disease, or a neorodegenerative disease with these compounds.

Palladium(0)/copper(I)-cocatalyzed cross-coupling of the zinc reagent of ethyl 3-bromo-3,3-difluoropropionate with aryl (alkenyl) halides: An efficient stereoselective synthesis of β-fluoro-α,β-unsaturated esters

Ethyl 3-bromo-3, 3-difluoropropionate was prepared in an overall yield of 75% from the radical addition of dibromodifluoromethane to ethyl vinyl ether under Na2S2O4 initiation, followed by oxidation of the acetal with Caro acid. The treatment of 1 with active zinc dust in anhydrous DMF at room temperature produced the zinc reagent ZnBrCF2CH2CO2C2H5 (2). The cross coupling of the zinc reagent 2 with aryl (alkenyl) halides (R-X) in DMF using Pd(0)-Cu(I) as cocatalyst stereoselectively provided the β-fluoro-α,β- unsaturated esters (RCF=CHCO2C2H5 4) directly and in moderate yields. An E/Z ratio ranging from 3:2 to 1:0 was observed. This is the first example that Cu(I) can improve the selectivity of the cross-coupling reaction. Mechanistic studies revealed that zinc reagent 2 underwent stereoselective elimination to produce (Z)-1-fluoro-2-(ethoxycarbonyl)ethenylzinc reagent 6, and then the cross-coupling of 6 with aryl(alkenyl) halides under palladium(O) catalysis afforded the β-fluoro-α,β-unsaturated esters 4.

A convenient synthesis of ethyl 3,3,3,-trifluoropropanoate and its 2-bromo derivative

Ethyl 3,3,3-trifluoropropanoate and ethyl 2-bromo-3,3,3-trifluoropropanoate have been synthesized. A common intermediate ethyl 3-chloro (or 3-bromo)-3,3-difluoropropanoate is involved in the two syntheses. These esters are obtained by oxidation of the corresponding acetals resulting from the radical addition of CF2BrCl or CF2Br2 to ethyl vinyl ether.