Cyclohexyl acetate, hydrolysis

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) ... 

The kinetics of the hydrolysis reactions of 4-amino-2-phenethyl- (354 R = PhCH2CH2) and 4-amino-2-cyclohexyl-2,3-dihydro-3-oxo-l,2,5-thiadiazole 1,1-dioxide (354 R = CeHii) have been investigated in the pH range 1-10 at 24-73 °C. The products are the corresponding new compounds 2-anuno-2-[(A -substituted-sulfamoyl)imino]acetic acid salts (355 R = PhCH2CH2 or CeHn) which hydrolyse further, in a slow reaction, to the sulfamide and oxalic acid derivatives. ... 

Fig. 19- The efficiency, q, of the Amberlite IR-120 ion exchanger catalyst in ester hydrolysis as a function of the entropy, S, of the parent hydrocarbon RH or R H of the substituents, (a) Hydrolysis (at 25—45°C) of methyl esters RCOOCH3 [366] 1, acetate 2, chloroacetate 3, benzoate 4, cyclopentanecarboxylate 5, phenylacetate 6, a-naphthylacetate 7, 1-octanoate. (b) Hydrolysis (at 35°C) of acetates CH3COOR [480] 1, methyl 2, ethyl 3, cyclopentyl 4, cyclohexyl 5, 1-butyl 6, 2-pentyl 7, 1 -pentyl 8, 1 -hexyl 9, 1 -octyl,...

Another example using a prochiral acetate and asymmetric hydrolysis was described by the Bristol-Myers Squibb group for an intermediate in the synthesis of Monopril (fosinopril sodium) (41), an ACE inhibitor (Scheme 19.23). The prochiral substrate 42 was hydrolyzed both when R = phenyl or cyclohexyl to the corresponding (S)-(-)-monoacetate 43. The reaction was carried out in a 10% toluene biphasic system with either PPL or Chromobacterium viscosum lipase. The cyclohexyl monoacetate was obtained in 90% yield with an optical purity of 99.8%.107 195... 

Danishefsky and coworkers have demonstrated the conversion of lactones to carbocycles by the 3,3-sigmatropic shift of silylketene acetals. Jq the total synthesis of the Fusarium toxin equisetin, for example, keto lactone (138) was converted to its bissilyl derivative (139) by reaction with 2 equiv. of LDA and an excess of TMS-Cl. In situ thermolysis of ketene acetal (1 ) led to a very smooth transformation into ester (140), which was carried on to equisetin (Scheme 26). This methodology was also applied by Schreiber and Smith in the preparation of the cyclohexyl moiety of the immunosuppressive agent FK-506. Ireland-Claisen rearrangement of silylketene acetal (142), prepared by treatment with TBDMS-OTf and triethylamine at low temperature, provided, after hydrolysis of the silyl ester, the carboxylic acid (143) in 71% overall yield (Scheme 27). The strict translation of configuration via a boatlike transition state is typical for this permutation. 

Piperazine-2,3,5-trione has been prepared from aminoacetamide and diethyl oxalate in methanolic sodium methoxide (365b). Oxanilic acid (PhNHCOCOOH) refluxed with thionyl chloride gave 1,4-diphenylpiperazinetetraone (identical with authentic material obtained by chromic acid oxidation of 1,4-diphenylpiperazine-2,5-dione) (1640). Hydrolysis of 3,3,5,5,6,6-hexachloro-4-cyclohexyl-I-phenyl-piperazin-2-one by heating at 100° with aqueous acetic acid gave l-cyclohexyl-4-phenylpiperazinetetraone (probably) (853). 

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)-... 

COCH3 - Preparation by reaction of acetic acid with 4-cyclohexyl-resorcinol in the presence of boron trifluoride etherate at 105-108° for 15 min, followed by hydrolysis of the obtained boron difluoride chelate (m.p. 207-208°) with boiling aqueous ethanol for 15-20 min (89%) [3548]. 

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