2-Oxazolidinone → 2(R)-(4-thiazolylmethyl)butanedioic acid

4-{[1(S)-(Cyclohexylmethyl)-2(R),3(S)-dihydroxy-5-methylhexyl]amino}-4-oxo-3(R)-(4-thiazolylmethyl)butanoic Acid: The desired 2-oxazolidinone of the previous section (4.02 g, 10.5 mmol) was reacted with lithium hydroxide-hydrogen peroxide according to the procedure of section C(g) of this example to give the monoprotected dicarboxylic acid of formula 2, i.e. the 4-tertbutyl ester of 2(R)-(4-thiazolylmethyl)butanedioic acid. Subsequent coupling of the latter compound (2.83 g, 10.4 mmol) with 2(S)-amino-1-cyclohexyl-6-methyl-3(R),4(S)-heptanediol hydrochloride (3.21 g, 11.5 mmol) according to the coupling procedure section C(g) of this example gave the desired protected amido acid of formula 3 wherein W1 is tert-butoxy, R2 is 4-thiazolylmethyl and B is 1(S)-(cyclohexylmethyl)-2(R),3(S)-dihydroxy-5-methylhexyl, as a white solid (3.75 g, 72%); 1H NMR (CDCl3) δ8.70 (s, 1H), 7.10 (s,1H), 5.96 (d, J=8.3 Hz, 1H), 4.40-4.25 (m,2H), 3.40-2.70 (m,6H), 2.40 (dd, J=4.4 Hz,16.8 Hz, 1H), 1.95-1.10 (m, 17H), 1.40 (s,9H), 0.90 (d, J=6.6 Hz, 3H), 0.80 (d, J=6.4 Hz, 3H). The latter compound was deprotected as follows: The compound (3.7 g, 7.45 mmol) was dissolved in CH2Cl2 (30 mL). Under a N2 atmosphere at 0°, TFA (6 mL) was added to the solution. The reaction mixture was stirred for 5.5 h. At this point, another portion of TFA (6 mL) was added to the reaction mixture at 0°. The mixture was stirred at room temperature for 3 h. Thereafter, the mixture was diluted with Et2O and concentrated to dryness under reduced pressure to give the desired amido acid (4.70 g); FAB mass spectrum, m/z: 441 (M+H)+. The compound was used without further purification for ensuing coupling steps.

ORD 기록

ord-7a3fb0ed45244dcebf73b5e6750a04cf

출처 데이터셋

uspto-grants-1996_06

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US05523315