Septum-sealed reaction vials

In 2002, Alterman and coworkers exploited this concept and developed a micro-wave-promoted carbamoylation protocol using DM F as the in situ carbon monoxide liberator in septum-sealed reaction vials [40]. It was discovered that aryl dimethyl amides were accessible from the corresponding bromides in the presence of KOt-Bu and the nucleophilic catalyst, imidazole (Scheme 4.27). Moreover, tertiary benza-mides other than dimethylamides were prepared by adding 3 equiv. of an external primary or secondary amine. This in situ carbon monoxide generation methodology... 

To a thick-walled, septum-sealed glass vial, equipped with a magnetic stir-bar was added 5-butylnorbornene (7.57 g, 50.4 mmol), triethoxysilylnorbornene (0.68 g, 2.6 mmol), toluene (8mL), palladium ethyl hexanoate (2.6 pmol), tricyclo-hexylphosphine (2.6 pmol), tris(pentafluorophenyl)boron (23.4 pmol) and triethyl-aluminum (26 pmol) (ratio of monomers to palladium 20000 1). The resulting stirred solution was placed in a heated oil bath at 65 °C. Within 30 s the reaction exothermed violently resulting in a solid mass that no longer stirred within 45 s. 

MAT 311A instrument operating at 70 eV [electron impact (El) mode] and reported as m/z and relative intensity (%). Field desorption (FD) mass measurements were carried out on a ZAB 2-SE-FDP instrument. Microwave-assisted synthesis was performed using a CEM-Discovery monomode microwave system utilizing an IR temperature sensor and magnetic stirrer in sealed 10 -mL glass vials with aluminum caps and a septum. All reactions were monitored and controlled using a personal computer. 

STEP1/WAIT2 implied the addition of 8.25a or 8.25b (0.04 mL, stock solution) to septum-sealed 1.8-mL vials followed by the monomer set Mi (0.026 mL, stock solution). The reactions were left standing for 10 min at room temperature WAIT2). 

Only resublimed DNA-grade tetrazole should be used this is available from Sigma in septum-sealed, argon-filled vials containing 300 mg of material, sufficient for carrying out a 0.1-mmol-scale reaction. Dibenzyl-Af,N-diisopropylphosphoramidite is available in argon-filled one-shot vials from Novabiochem. 

In 2003, the microwave-assisted coupUng of aryl hahdes with acetylenes using a palladium catalyst were carried out employing a modified Smith Process vial [49]. These vessels, equipped with a polypropylene frit and screw cap at the bottom, and sealed with an aluminum crimp cap fitted with a silicon septum at the top (Fig. 8), faciUtated the processing of approximately 1 g of solid support. Notably, they are compatible with stirring of the reaction mixture and monitoring of the temperature and pressure. 

When capped, the vial is a sealed system, consequently this set-up is only useful for small scale reactions at room temperature that do not involve an increase or decrease in pressure inside the reaction vessel. For reactions at low temperature, or those requiring a positive pressure of an inert gas atmosphere, it is often more convenient to use a Pyrex test tube fitted with a septum (Fig. 12.3). 

A 4-mL vial was charged with bromobenzene (63 mg, 0.40 mmol), Pdtdbaii (11.5 mg, 0.0200 mmol), Ph5FcP-(Z-Bu)2 (14.2 mg, 0.0200 mmol), and sodium zcrt-butoxide (47 mg, 0.48 mmol). Anhydrous toluene (2 mL) was added, and the vial was sealed with a cap containing a PILE septum and removed from the dry box. The reaction mixture was stirred at room temperature for 23 h. The reaction solution was then adsorbed onto silica gel, and the product was isolated by eluting with EtOAc/hexanes (0 to 10% gradient) to give the ether (58 mg, 97%). 

A microwave process vial was charged with a stir bar. To this vessel were added DHPM (69.1 mg, 0.25 mmol), 45.7 mg PhB(OH)2 (0.375 mmol), 142.9 mg Cu(I) thiophene-2-carboxylate (CuTC) (0.75 mmol), and 8.7 mg Pd(PPhs)4 (3.0 mol %). The reaction vessel was flushed with argon and sealed. Through the septum was added 5 mL anhydrous THF, and the reaction vessel was irradiated at 100°C for 25 min. After cooling, the mixture was transferred to a round-bottomed flask and was adsorbed on silica gel. The residue was purified by flash chromatography on silica gel (hexanes/EtOAc, 3 1) to yield 81% dihydropyrimidine as a semisolid. 

Reaction Working at the hood, transfer 0.2 mL of thionyl chloride into the vial using a graduated pipet. Seal the joint of the straight portion of the adapter with a rubber septum. The apparatus may now be moved to your desk if desired. Heat the mixture under gentle reflux for 15 min. The bubbling that is initially observed should slow during the reflux period and the reaction mixture should become clear. 

To a screw-capped vial containing the NHC precursor (Scheme 8.56) (0.005 mmol), Pd(dba)2 (0.005 mmol), and LiHMDS (2.3 mmol) are added 2-bromo-l,3,5-trimethylbenzene (1.0 mmol) and tert-butyl acetate (1.1 mmol) followed by toluene (2.5 ml) [101]. The vial is sealed with a cap containing a PTFE septum and removed from the drybox. The heterogeneous reaction mixture is stirred at room temperature for 12 h. The crude reaction is diluted with EtjO and quenched with aqueous NH Cl. The organic phase is washed with a saturated aqueous... 

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