Chloromethyl pivalate

Another synthesis avoids the isolation of 6-APA and starts directly with penidllin G. Reaction with chloromethyl pivalate gives its pivaloyloxymethyl ester. This reacts with PCI5 to an imidoyl chloride which may be solvolyzed with propanol. The add chloride of (R)-... 

A) PivaloyloxymethylD(—j-Oi-azidobenzylpenicillinate Toa suspension ofpotassiumD(—)-a-azidobenzylpenicillinate (4.14g) and potassium dicarbonate (1.5 g) in acetone (100 ml) and 10% aqueous sodium iodide (2 ml), chloromethyl pivalate (2.7 ml) was added and the mixture refluxed for 2 hours. After cooling, the suspension was filtered and the filtrate evaporated to dryness in vacuo. The remaining residue was washed repeatedly by decantation with petroleum ether to remove unreacted chloromethyl pivalate. The oily residue was taken up in ethyl acetate (100 ml), and the resulting solution washed with aqueous sodium bicarbonate and water, dried and evaporated in vacuo to yield the desired compound as a yellowish gum, which crystallized from ether, melting point 114°C to 115°C. 

The esterification of 1,2,5-dithiazepine 68 with phenylphosphonic dichloride in benzene and subsequent hydrolysis gave 122, which upon further esterification with chloromethyl pivalate in MeOH afforded 0-(l,l,4,4-tetramethyl-2,3,5,6,9,10-hexahydroimidazo[2,, 2,5]dithiazepin-9-yl )cthy 10-pi valoyloxy methyl phenylphosphonate 123... 

Recently , several new bifunctional, carbon-11 labelled synthons have been prepared from the starting material, chloromethyl pivalate, in at least a 90% yield using the microwave technique (Scheme 4). The comparable reaction times using conventional heating methods are shown for comparison in Table 1. These labelled bifunctional molecules, which can be prepared and purified in minutes, expand markedly the number of molecules that can be prepared with carbon-11 cyanide. 

The alkylation of IcP by chloromethyl pivalate in the presence of K2CO3 in DMF provided a mixture of 1- and 3-pivaloyloxymethyl derivatives in 7.5 2.5 ratio in 88% overall yield (86T1511). 

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