2- ethyl carbonate alcohol protection

Triphenylphosphonio)ethyl carbonates, to protect alcohols, 107 2-(Triphenylphosphonio)isopropyl carbamates, to protect amines, 326, 342 Triphenylsilyl ethers, to protect alcohols,... 

The reactivity of various steroid alcohols decreases in the order primary > secondary (equatorial) > secondary (axial) > tertiary. The only systematic investigation relating to the selective protection of steroidal hydroxyl functions has been carried out with the cathylate (ethyl carbonate) group. Since only equatorial hydroxyl groups form cathylates this ester has been used as a diagnostic tool to elucidate the configuration of secondary alcohols. 

The synthesis of key intermediate 12, in optically active form, commences with the resolution of racemic trans-2,3-epoxybutyric acid (27), a substance readily obtained by epoxidation of crotonic acid (26) (see Scheme 5). Treatment of racemic 27 with enantio-merically pure (S)-(-)-1 -a-napthylethylamine affords a 1 1 mixture of diastereomeric ammonium salts which can be resolved by recrystallization from absolute ethanol. Acidification of the resolved diastereomeric ammonium salts with methanesulfonic acid and extraction furnishes both epoxy acid enantiomers in eantiomerically pure form. Because the optical rotation and absolute configuration of one of the antipodes was known, the identity of enantiomerically pure epoxy acid, (+)-27, with the absolute configuration required for a synthesis of erythronolide B, could be confirmed. Sequential treatment of (+)-27 with ethyl chloroformate, excess sodium boro-hydride, and 2-methoxypropene with a trace of phosphorous oxychloride affords protected intermediate 28 in an overall yield of 76%. The action of ethyl chloroformate on carboxylic acid (+)-27 affords a mixed carbonic anhydride which is subsequently reduced by sodium borohydride to a primary alcohol. Protection of the primary hydroxyl group in the form of a mixed ketal is achieved easily with 2-methoxypropene and a catalytic amount of phosphorous oxychloride. 

Ethyl 5-oxohexanoate (51) was reduced with NaBH4 and the resulting alcohol protected with dihydropyran to give 52. Reduction of the ester moiety to a primary alcohol followed by conversion to the bromide 53 was achieved by conventional means. Alkylation of the dianion of ethyl acetoacetate with 53 afforded a 78% yield the p-keto ester 54, which possesses all the carbons required for the construction of the diplodialides. Protection of the ketone as the dithiane... 

Ethyl a-phenylacetoacetate can be prepared by the hydrolysis of a-phenylacetoacetonitrile in absolute alcohol with dry hydrogen chloride.1 The present method differs in specifying neutralization of the hydrogen chloride with sodium carbonate and hydrolysis of the imino ether in aqueous sulfuric acid, so that the product separates as fast as it forms, thus being protected from further decomposition, with a considerably increased yield as the result. 

Prepare 26 g. of molecular sodium in a 1500 ml. round-bottomed flask (Section II,50,d, Method 1). Cover the sodium with 625 ml. of sodium-dried A.R. benzene fit the flask with an efficient reflux condenser protected from the air by means of a calcium chloride (or cotton wool) guard tube. Add 151 5 g. of diethyl adipate (Sections 111,99 and 111,100) in one lot, followed by 1 6 ml. of absolute ethyl alcohol. Warm the flask on a water bath until, after a few minutes, a vigorous reaction sets in and a cake of the sodio compound commences to separate. Keep the flask well shaken by hand during the whole of the initial reaction. After the spontaneous reaction has subsided, reflux the mixture on a water bath overnight, and then cool in ice. Decompose the product with ice and dilute hydrochloric acid (1 1) add the acid until Congo red paper is turned blue. Separate the benzene layer, and extract the aqueous layer with 100 ml. of benzene. Wash the combined extracts with 100 ml. of 5 per cent, sodium carbonate solution and 160 ml. of water dry over a KWe anhydrous magnesium sulphate. Remove the benzene under atmospheric pressure (Fig. II, 13, 4, but with modified Claisen flask), and fractionate the residue under reduced pressure. Collect the 2-carbethoxy-epelopentanone at 108-111°/15 mm. (96 g.). Upon redistillation, the product boils at 102°/H mm. 

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