methyl (2S)-2-amino-3-hydroxypropanoate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (S)-N-isobutylserine methyl ester HCl salt was made from (L)-serine methyl ester as described in Method B3a. The ester was reacted with SOCl2, followed by 2-methyl-4-nitrophenyl isothiocyanate according to Method C2a to afford (4R)-2-(2-methyl-4-nitrophenylimino)-4-(methoxycarbonyl)-3-isobutyl-1,3-thiazolidine HCl salt.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (S)-N-isobutylserine methyl ester HCl salt was made from (L)-serine methyl ester as described in Method B3a. The ester was reacted with SOCl2, followed by 2-methyl-4-nitrophenyl isothiocyanate according to Method C2a to afford (4R)-2-(2-methyl-4-nitrophenylimino)-4-(methoxycarbonyl)-3-isobutyl-1,3-thiazolidine HCl salt.

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of benzyloxycarbonylglycyl-glycine (13.31 g, 50 mmoles), N-hydroxysuccinimide (5.75 g) and N, N'-dicyclohexylcarbodiimide (11.3 g) in dimethylformamide (180 ml) is stirred and cooled (-10° C.) for 1 hour. A precooled (-10° C.) solution of serine methyl ester, liberated from its hydrochloride (7.8 g, 50 mmoles) with N-ethylpiperidine (6.85 ml), in the same solvent (50 ml) is added, and the reaction mixture is stirred for 3 hours at 0° C. and allowed to stand for 8 hours at room temperature; the N, N'-dicyclohexylurea precipitate is filtered off and the filtrate is admixed with 100% hydrazine hydrate (15 ml). After 3 days of standing at room temperature, the formed hydrazide is separated, washed with ethanol and crystallized from aqueous ethanol. Yield 15.2 g (83%), m.p. 172-175 (unchanged after recrystallization). Composition: C15H21N5O6. is added to stand for 8 hours at room temperature the N, N'-dicyclohexylurea precipitate is filtered off After 3 days of standing at room temperature the formed hydrazide is separated washed with ethanol crystallized from aqueous ethanol Yield 15.2 g (83%), m.p. 172-175 (unchanged after recrystallization)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Serine methyl ester (1.0 moles, 0.119 g), diisopropylethylamine (1.0 mmoles, 0.206 g), 2-[5-[2-(2H-tetrazol-5-yl)phenyl]-1H-benzimidazol-1-yl]octanoic acid (1.0 mmoles, 0.405 g), hydroxybenzotriazole (1.0 mole, 0.135 g), and dicyclohexylcarbodiimide (1.0 moles, 0.206 g) were reacted as in Example 37. The resulting ester (0.19 moles, 0.097 g) was hydrolyzed as in Example 37 to yield 0.052 g of N-[1-oxo-2-[5-[2-(2H-tetrazol-5-yl]phenyl]-1H-benzimidazol-1-yl]octyl]-L-serine (MS).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Serine methyl ester (1.0 moles, 0.119 g), diisopropylethylamine (1.0 mmoles, 0.206 g), 2-[5-[2-(2H-tetrazol-5-yl)phenyl]-1H-benzimidazol-1-yl]octanoic acid (1.0 mmoles, 0.405 g), hydroxybenzotriazole (1.0 mole, 0.135 g), and dicyclohexylcarbodiimide (1.0 moles, 0.206 g) were reacted as in Example 37. The resulting ester (0.19 moles, 0.097 g) was hydrolyzed as in Example 37 to yield 0.052 g of N-[1-oxo-2-[5-[2-(2H-tetrazol-5-yl]phenyl]-1H-benzimidazol-1-yl]octyl]-L-serine (MS).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Serine methyl ester (1.0 mmoles, 0.119 g), diisopropylethylamine (1.0 mmoles, 0.206 g), 2-[5-[2-(2H-tetrazol-5-yl)phenyl]-1H-benzimidazol-1-yl]octanoic acid (1.0 mmoles, 0.405 g), hydroxybenzotriazole (1.0 mole, 0.135 g), and dicyclohexylcarbodiimide (1.0 moles, 0.206 g) were reacted as in Example 37. The resulting ester (0.19 moles, 0.097 g) was hydrolyzed as in Example 37 to yield 0.052 g of N-[1-oxo-2-[5-[2-(2H-tetrazol-5-yl]phenyl]-1H-benzimidazol-1-yl]octyl]-L-serine (MS).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Serine methyl ester (1.0 mmoles, 0.119 g), diisopropylethylamine (1.0 mmoles, 0.206 g), 2-[5-[2-(2H-tetrazol-5-yl)phenyl]-1H-benzimidazol-1-yl]octanoic acid (1.0 mmoles, 0.405 g), hydroxybenzotriazole (1.0 mole, 0.135 g), and dicyclohexylcarbodiimide (1.0 moles, 0.206 g) were reacted as in Example 37. The resulting ester (0.19 moles, 0.097 g) was hydrolyzed as in Example 37 to yield 0.052 g of N-[1-oxo-2-[5-[2-(2H-tetrazol-5-yl]phenyl]-1H-benzimidazol-1-yl]octyl]-L-serine (MS).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Oxazoles and Oxazolines Yokokawa (Synthetic Lett., 1992, 2, 153) has recently described the preparation and cyclization of N-acylserine ester derivatives to give 2-substituted-4,5-dihydrooxazole-4-carboxylate esters which, after oxidation, give the corresponding 2-substituted-oxazole-4-carboxylate esters. By inference, N-acylation of serine methyl ester with t-butoxyacetic acid, followed by cyclization, oxidation, deprotection and conversion to the chloride by standard methods should give methyl 2-(chloromethyl)oxazole-4-carboxylate, as outlined in Scheme XX below. Eliminiation of the oxidation step will give the corresponding oxazoline. ##STR52##

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Serine methyl ester (1.0 mmoles, 0.119 g ), diisopropylethylamine (1.0 mmoles, 0.206 g), 2-[5-[2-(2H-tetrazol-5-yl)phenyl]-1H-benzimidazol-1-yl]octanoic acid (1.0 mmoles, 0.405 g), hydroxybenzotriazole (1.0 mmole, 0.135 g), and dicyclohexylcarbodiimide (1.0 mmoles, 0.206 g) were reacted as in Example 37. The resulting ester 0.19 moles, 0.097 g) was hydrolyzed as in Example 37 to yield 0.052 g of N-[1-oxo-2-[5-[2-(2H-tetrazol-5-yl]phenyl]-1H-benzimidazol-1-yl]octyl]-L-serine (MS).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Serine methyl ester (1.0 mmoles, 0.119 g ), diisopropylethylamine (1.0 mmoles, 0.206 g), 2-[5-[2-(2H-tetrazol-5-yl)phenyl]-1H-benzimidazol-1-yl]octanoic acid (1.0 mmoles, 0.405 g), hydroxybenzotriazole (1.0 mmole, 0.135 g), and dicyclohexylcarbodiimide (1.0 mmoles, 0.206 g) were reacted as in Example 37. The resulting ester 0.19 moles, 0.097 g) was hydrolyzed as in Example 37 to yield 0.052 g of N-[1-oxo-2-[5-[2-(2H-tetrazol-5-yl]phenyl]-1H-benzimidazol-1-yl]octyl]-L-serine (MS).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Proceeding in a like manner but substituting the appropriate aldehyde of formula (6) as prepared in Preparation 4, or the appropriate ketone of formula (8) as prepared in either Preparation 6 or 9, and either L-serine methyl ester or a racemic mixture of D,L-serine methyl ester or similar ester, there are prepared the following exemplary compounds: as prepared in Preparation 4 are prepared the following exemplary compounds

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Proceeding in a like manner but substituting the appropriate aldehyde of formula (6) as prepared in Preparation 4, or the appropriate ketone of formula (8) as prepared in either Preparation 6 or 9, and either L-serine methyl ester or a racemic mixture of D,L-serine methyl ester or similar ester, there are prepared the following exemplary compounds: as prepared in Preparation 4 are prepared the following exemplary compounds