Process for preparing 4-amino-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-pentanoic acid compound
The invention provides processes for preparing intermediates useful for preparing compounds of the formula: or a tautomer or salt thereof, where R 1 -R 5 , a, b, X and P 2 , are as defined in the specification.
1. A compound of formula II:
where:
a is 0 or 1; R 4 is selected from halo, —CH 3 , —CF 3 , and —CN;
b is 0 or an integer from 1 to 3; and each R 5 is independently selected from halo, —OH, —CH 3 , —OCH 3 , and —CF 3 ;
T is H or P 2 , where P 2 is an alcohol protecting group; and
U is H or P 3 , where P 3 is an amino protecting group;
or a salt thereof.
2. The compound of claim 1 , where P 2 is selected from acetyl, benzoyl, benzyl, p-methoxybenzyl ether, β-methoxyethoxymethyl ether, methylthiomethyl ether, pivaloyl, silyl ethers, tetrahydropyranyl, triphenylmethyl, and trityl.
3. The compound of claim 2 , where T is H or tetrahydropyranyl.
4. The compound of claim 1 , where P 3 is selected from acetyl, adamantyl-oxycarbonyl, t-amyloxycarbonyl, benzothiophene sulfone-2-methoxycarbonyl, benzoyl, benzyl, benzyloxycarbonyl, 2-(p-biphenylyl)propyl-2-oxycarbonyl, t-butoxycarbonyl, 2-(t-butylsulfonyl)-2-propenyloxycarbonyl, 3,4-dimethoxybenzyl, 2,2-dimethyl-3,5-dimethyloxybenzyloxycarbonyl, dithiasuccinoyl, formyl, 9-fluorenylmethoxycarbonyl, 2-furanmethyloxycarbonyl, p-methoxybenzyl, p-methoxybenzyl carbonyl, 1-methylcyclobutyloxycarbonyl, o-nitrophenylsulfenyl, 2-phenylpropyl-2-oxycarbonyl, 2-(p-phenylazophenyl)propyl-2-oxycarbonyl, silyl ethers, tosyl, trifluoroacetyl, β-trimethylsilylethyloxycarbonyl, triphenylmethyl, and trityl.
5. The compound of claim 4 , where U is H or t-butoxycarbonyl.