A New Synthesis of Roxatidine Acetate

Phenoxypropylamines: Synthesis and Antiulcer Evaluation

“…N -{3-[3-(1-Piperidinymethyl)phenoxy]propyl}chloroacetamide ( 3 ) was synthesized by a three-step reaction from m -hydroxybenzaldehyde. The hydrochloric acid salt of roxatidine acetic ester 4 was prepared in 28.8% yield by the reaction of 3 with AcOK [ 2 ]. Six phenoxypropylamine derivatives were then synthesized by the reaction of 3 with primary amines, followed by oxalic acid to obtain their corresponding salts 6 .…”

“…136-138°C. IR (KBr): 2900, 3400 cm -1 ; MS m/z (%): 191 (M + , 18), 107 (49), 84 (100); 1 H-NMR: 1.41-1.42 (d, 2H, J = 5), 1.56-1.59 (m, 4H, J =7), 2.43 (s, 4H), 3.41 (s, 2H), 6.44 (bs, 1H), 6.66-6.70 (d,2H, J = 8 ), 6.75-6.77 (d,1H, J = 8), 7.08-7.13 (t,1H, J =8) [ 2 ].…”

“…This solution contains 12.04 g (97%) of 2 and is directly used in the next step without isolation. Oily substance; IR (film): 2925, 3300 cm -1 ; MS m/z (%): 248 (M+, 7.46), 190 (2.81), 165 (10.49), 107 (8.84), 98 (24.76), 84 (100); 1 H-NMR δ: 1.36 (bs, 2H, J =5), 1.41-1.43 (d, 2H, J =5), 1.53-1.60 (m, 4H, J =5), 1.87-1.96 (m, 2H, J =7), 2.36 (s, 4 H ), 2.89-2.92 (t, 2H, J =7), 3.43 (s, 2H), 4.02-4.06 (t, 2H, J =7), 6.75-6.79 (dd, 1H, J =8), 6.87-6.89 (d, 2H, J =8), 7.17-7.22 (t, 1H, J =8) [ 2 ].…”

“…The solvent is evaporated and the residue dried in vacuo to give 13.04 g (98.0%) of 3 as a colorless, partially crystallized oily substance. IR (film): 1670, 2940, 3000, 3400 cm -1 ; MS m/z (%): 324 (M+, 10), 240 (1.74), 190 (5.25), 134 (74.6), 84 (100); 1 H-NMR: 1.41-1.43 (d, 2H, J =5), 1.53-1.60 (m, 4H, J =5), 1.90 (s, 1H), 2.01-2.09 (m, 2H, J =7), 2.37 (s, 4 H), 3.44 (s, 2H), 3.51-3.57 (m, 2H, J =7), 4.06 (s, 2H), 4.07-4.11 (t, 2H, J =7), 6.77-6.80 (dd, 1H, J =8), 6.90-6.92 (d, 2H, J =8), 7.19-7.24 (t, 1H, J = 8) [ 2 ].…”

“…In this paper we describe the preparation and antiulcer activity of compounds 6a -6f . Roxatidine acetate ( 4 ) was synthesized by a series of reaction including Leukart reductive amination, acylation and substitution [ 2 ]. On the basis of the bioisosterism principle phenoxypropylamines were prepared from compound 3 using primary amines [ 3 ].…”