Approaches to the synthesis of sterically hindered amines

wo routes to prepare sterically hindered amines were investigated. Route one involved oxidative cleavage of 2,2,6,6-tetramethyl-4-piperidone 41.;Potassium permanganate oxidation of 41 and by esterification afforded the ring cleaved diester, dimethyl-N-(2-carboxy-2-propyl)-3-amino-3,3-dimethylpropionate 46 and the ring contracted ;Hydrolysis of 58 afforded the sodium-2,2,5,5-tetramethyl-3-hydroxypyrrolidine-3-carboxylate 59. Decarboxylation of 59 afforded the known 2,2,5,5-tetramethyl-3-pyrrolidone 60. Reduction of 58 gave the diol 2,2,5,5-tetramethyl-3-hydroxy-3-hydroxymethylpyrrolidine 61. Hydrolysis of 46 afforded the known disodium-N-(2-carboxy-2-propyl)-3-amino-3,3-dimethylpropionate 62.;Permanganate cleavage of 4-piperidone monohydrate hydrochloride 63 afforded the known ring cleaved diester dimethyl-N-carboxymethyl-3-aminopropionate 64. Diester 64 could also be prepared by a Michael reaction of glycine methyl ester with methyl acrylate. Treatment of 64 with sodium hydroxide afforded the disodium-N-carboxymethyl-3-aminopropionate 67.;1,2,2,6,6-Pentamethyl-4-piperidone 68 was prepared by alkylating 41 in the presence of diisopropylethylamine. The 1,2,2,5,5-pentamethyl-3-hydroxy-3-carbomethoxypyrrolidine 69 was similarly prepared by N-alkylation of 58. Permanganate oxidation of 68 afforded again 58.;Treatment of 2,2,6,6-tetramethyl-piperidine-3,4-dione 82 with base and further reduction afforded the 4-hydroxy-2,2,6,6-tetramethyl-3-piperidione 86.;Treatment of 41 with bromine in acetic acid afforded the 3-bromo-2,2,6,6-tetramethyl-4-piperidone hydrobromide 91. Refluxing 91 in water afforded 5,5-dimethyl-2-isopropyl-1-pyrrolin-3-one 92. Heating a mixture of 91, sodium acetate and acetic anhydride to 95;Route two investigated the potential ring opening of...