2-Chloro-2-methylbutane preparation

The submitters purchased 2-chloro-2-methylbutane from Eastman Kodak Company. The checkers prepared the halide as follows. A separatory funnel was charged with 21.5 mL (0.2 mol) of 2-methyl-2-butanol and IQO mL of coned hydrochloric acid. The mixture was shaken vigorously with periodic venting for 10 min. The layers were separated and the 2-chloro-2-methylbutane layer (upper) was washed several times with equal volumes of cold water. The product was dried over calcium chloride and distilled, bp 85 C. 

This potent inhibitor of cholesterol biosynthesis has been synthesized178 by one-pot esterification of the alcohol 210 with the acid chloride of 2,2-dimethylbutanoic[l-14C] acid, obtained by carbonation of the Grignard reagent prepared from 2-chloro-2-methylbutane (equation 74). Desilylation of 211 afforded [14C]simvastatin 209 in 29% radiochemical yield from 14C-labelled C02. This 14C-labelled drug was needed for elucidation of its metabolic fate in experimental animals. 

Chlorohydnns, preparation from a-chloro acids, 66, 161 (S )-2-Chloro-3-methylbutan-l-ol, 66, 164... 

In a multistep synthesis, the overall percent yield is the product of the fractional yields in each step times 100 and decreases rapidly with the number of steps. For this reason, a low-yield step along the way can mean practical failure for the overall sequence. Usually, the best sequence will be the one with the fewest steps. Exceptions arise when the desired product is obtained as a component of a mixture that is difficult to separate. For example, one could prepare 2-chloro-2-methylbutane in one step by direct chlorination of 2-methyl-butane (Section 4-5A). But because the desired product is very difficult to separate from the other, isomeric monochlorinated products, it is desirable to use a longer sequence that may give a lower yield but avoids the separation problem. Similar separation problems would be encountered in a synthesis that gives a mixture of stereoisomers when only one isomer is desired. Again, the optimal synthesis may involve a longer sequence that would be stereospecific for the desired isomer. 

Cognate preparation. 2-ChIoro-2-methylbutane. Use 22 g (27 ml, 0.25 mol) of 2-methylbutan-2-ol (t-pentyl alcohol) and 65 ml of concentrated hydrochloric acid. Distil the chloride twice from a Claisen flask with fractionating side-arm or through a short column. Collect the 2-chloro-2-methylbutane at 83-85 °C the yield is 18 g (68%). Record the p.m.r. spectrum (CC14, TMS) and assign the signals which appear at 51.01 (t, 3H), 1.51 (s, 6H) and 1.73 (q, 2H) note the overlap of the latter two signals. 

Cognate preparations. The following alkyl chlorides may be prepared in similar yield by replacing the butan-l-ol in the above preparation by the appropriate quantity of the requisite alcohol 1 -chloropentane, b.p. 104-107 °C, from 22g of pentan-l-ol l-chloro-3-methylbutane, b.p. 98-100°C, from 22g of 3-methylbutan-l-ol (isopentyl alcohol) 2-chlorobutane, b.p. 67-69 °C, from 18.5 g of butan-2-ol. 

A freshly prepared solution of LDA [80 mmol, from i-PrjNH (8.88 g, 88 mmol) in THF (40 mL) and BuLi (2 M in hexane, 40 mL, 80 mmol) at 80 °C] in THF (40 mL) was treated rapidly with stirring and under Nj at 0 C with 3-chloro-3-methylbutan-2-one (4.82 g, 40 mmol). After the vigorous reaction had ceased, the mixture was magnetically stirred for an additional 1 h, then poured into H O (200 mL) and extracted with EtjO (3 x 70 mL). The combined extracts were dried (KjCOj) and evaporated in vacuo to afford an oil. After standing overnight, a white precipitate formed. The crystalline material was filtered, washed with pentane and dried in vacuo yield 1.7 g (47%) mp 110°C. 

Different reagents such as HX and PX3 may be used to prepare alkyl halides from primary and secondary alcohols. However, because elimination reactions predominate when tertiary alcohols are treated with phosphorous trihalides, preparing tertiary alkyl halides from tertiary alcohols proceeds with good yields only if concentrated hydrogen halides, HX, are used. The reaction of 2-methyl-2-butanol with hydrochloric acid to produce 2-chloro-2-methylbutane (Eq. 14.17) illustrates this transformation. 

Preparation by reaction of isoamyl chloride (l-chloro-3-methylbutane) with resbenzophenone (90%) [801]. 

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