Ferr-butyl ether

Optically active octyn-3-ol was obtained by first converting the salt 42 to the ester acids 43 and then hydrolysis of the ester to compound 44. Optical purity and assignment of the absolute configuration as S was established by methods known from analogous compounds from the literature. Fried and his co-worker proved that preparation of the ferr.-butyl-ether derivatives and deprotection with trifiuoroacetic acid is possible without a trace of racemisation. This guarantees that the S (normal) or the R (epi) 15-hydroxyprostanoids can be synthesized by using the resolved fert.-butylethers in the alkylation reaction. 

O-tert-Butyl trichloroacetimidate, prepared in 70% yield by reacting potassium rerr-butoxide with trichloroacetonitrile, reacts with carboxylic acids and alcohols in the presence of a catalytic amount of boron trifluoride etherate at room temperature in cyclohexane-dichloromethane [Scheme 6.35], 7 The method also converts alcohols to ferr-butyl ethers (see section 4.3.2). A very similar reaction that allows /erf-butylation under essentially neutral conditions on a large scale involves reaction of a carboxylic acid with 3-4 equivalents of JV,N -di-isopropyl-Orerf-butylisourea88 [Scheme 6,36].56S9 The reaction proceeds via a tertiary carbocation ion intermediate and since capture of the cation is inefficient, excess isourea is required. The presence of alcohols is tolerated but not thiols or unhindered amines. The reaction conditions are compatible with a range of acid sensitive groups such as AMrityl derivatives and cydopentylidene acetals.90... 

ACN = acetonitrile BuOH = butanol MBE = methyl ferr-butyl ether MP = mobile phase SP = DEHPA = di-[2-ethylhexyl]phosphoric acid TEA = trifluoroacetic acid MP = mobile phase SP... 

The two possible combinations of alkyl bromide and alkoxide ion that might yield ferr-butyl methyl ether are... 

A soln. of ferr-butyl-N-crotonylideneamine in petroleum ether added at 0-5 during 2 hrs. to a stirred soln. of phosgene in dry petroleum ether, and kept 2 hrs. at 10-20 N-fcrf-butyl-N-(3-chlorobuten-l-yl)carbamyl chloride (Y 96%) heated 2 hrs. at 110° in vacuo until HCl-elimination is complete N-(l,3-buta-dien-l-yl)-N-tcrt-butylcarbamyl chloride (Y 94%). F. e., also reaction with satd. azomethines, s. H. IGefer, Synthesis 1972, 39. 

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