4- Hydroxy-cyclohexyl-acetic acid

The j8-hydroxy esters obtained by Reformatzki syntheses are very readily dehydrated, so that water is often lost on distillation and hydrolysis then dehydration is completed by heating with acetic anhydride, acetyl chloride, potassium hydrogen sulfate, formic acid, or sulfuric acid. Depending on the nature of the substituents present on the /9-carbon atom, the products are oc,P- or /9,y-unsaturated acids or mixtures of both.43 In a few exceptional cases <%,/ - or /9,y-unsaturated acids can be obtained at will from /9-hydroxy acids by choice of a suitable dehydrating agent an example of this is (1-hydroxy-cyclohexyl)acetic acid (1) which, according to Wallach,44 is converted by potassium hydrogen sulfate or phosphorus(v) oxide into (1-cyclohexenyl)-acetic acid (2) but by acetic anhydride into the isomer, cyclohexylideneacetic acid (3) ... 

Acetic acid 2-hydroxy-3-oxo-3-cyclohexylpropylester + Acetic acid 3-cyclohexyl-3-hydroxy-2-oxo-propyl ester (2f , 3 5 )-3-Acetoxy-2-hydroxy cyclohexanone 17)3-Acetoxy-10-hyrdoxyestr-4-ene-3-one... 

The reaction mixture was then dissolved in methylene chloride, the amine was removed by shaking with dilute hydrochloric acid, the reaction product was extracted from the organic phase by means of dilute sodium hydroxide solution and the alkaline solution was acidified with acetic acid to a pH value of 6. The l-hydroxy-4-cnethyl-6-cyclohexyl-2-pyridone precipitated in crystalline form. It was filtered off with suction, washed with water and dried. The yield was 1.05 g (49% of theory) melting point 143 C. 

Hydroxycyclohexyl-1-acetic acid l,2-Bis(l-hydroxy-l-cyclohexyl)ethane (40%) 342)... 

Preparation by reaction of 65% nitric acid with cyclohexyl 4-hydroxy-3-methoxyphenyl ketone in acetic acid at r.t. (75%) [1084]. 

Preparation by demethylation of cyclohexyl (4-hydroxy-3-methoxy-5-nitrophenyl) ketone with 48% hydrobromic acid in refluxing acetic acid for 20 h (55%) [1084]. 

A mixture of 5-oxo-3-methyl-5-cyclohexylpentene-2 acid 1-methyl ester and 5-oxo-3-methyl-5-cyclohexylpentene-3 acid 1-methyl ester was obtained by condensation of hexahydrobenzoyl chloride with p,p-dimethylacrylic acid methyl ester. 11.2 g of this mixture and a solution of 4.6 g of sodium acetate and 4 g of hydroxylamine hydrochloride were shaken for 20 hours at 25°C with a mixture of 8 ml of water and 15 ml methanol. Subsequently, a solution of 4 g of sodium hydroxide in 8 ml of water was then added, while cooling, shaken for 1 hour at room temperature. The mixture was extracted by means of benzene and the aqueous phase was acidified to reach a pH of 6. 3.5 g of l-hydroxy-4-methyl-6-cyclohexyl-2-pyridone were obtained melting point 144°C. 

Hydroxy-4-phenyl-P-lactams. The lithium enolate of (silyloxy)acetates (2) couple with the N-(trimethylsilyl)imine 3 to give 3-hydroxy-4-aryl- -lactams (4). The stereoselectivity depends in part on the size of the silyloxy group but mainly on the ester group. Use of either (+)- or (—)-/ra/w-2-phenyl-l-cyclohexyl (I) as the chiral auxiliary results entirely in a cw-/3-lactam (4) in 80% yield and 96-98% ee. Use of (-)-menthyl or of Oppolzer s D-isobornyl auxiliary (12,103-104) results in lower yields and enantioselectivity. The cyclocondensation with the ester 2 from (-)-l results in (3R,4S)-4 in 96% ee. On desilylation and acid hydrolysis, this lactam provides (2R,3S)-... 

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