(2S)-1-((tert-butoxy)carbonyl)piperidine-2-carboxylic acid → 1-[(Tert-butoxy)carbonyl]piperidine-2-carboxylic acid

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Reaction Steps

N-Boc-L-pipecolic acid (0.280 g, 1.22 mmol) was esterified with 1-phenyl-7-(3'-pyridyl)-heptan-4-ol (0.394 g, 1.46 mmol) employing EDC hydrochloride (0.350 g, 1.83 mmol) and 4-dimethylaminopyridine (0.081 g, 0.663 mmol) in acetonitrile (25 mL). Purification by silica gel chromatography, eluting with chloroform/methanol (100:0 to 99:1), gave the pure 1-phenyl-7-(3'-pyridyl)-heptan-4-ol ester of N-Boc-pipecolic acid in 85% yield (0.498 g) as a colorless oil. MS: M+H=481. LC-MS: System 2 (4 min gradient), tR =3.8 min. A portion of this N-Boc ester (0.369 g, 0.768 mmol) was deprotected as described in example 1 with trifluoroacetic acid. The crude product was then coupled with α,α-difluoro-3,4,5-trimethoxyphenylacetic acid (0.241 g, 0.921 mmol), using EDC hydrochloride (0.220 g, 1.15 mmol) and 4-dimethylaminopyridine (0.101 g, 0.826 mmol) in acetonitrile (25 mL). After extractive work up as described in example 1, the product was purified by silica gel chromatography, eluting with hexane/ethyl acetate (4:1 to 1:1), to give the title compound (0.624 g, 1.05 mmol, 78%) as a pale yellow oil. MS: M+H=625. 1H-NMR: 8.38-8.34 (m, 2H), 7.75-7.00 (m, 7H), 6.76-6.63 (m & s, 2H), 5.25-4.10 (4×m, 2H), 3.80-3.50 (m, 1OH), 3.00-2.85 (m, 1H), 2.52 (m, 2H), 2.25-1.00 (4×m, 16H). LC-MS: System 2 (4 min gradient), tR, for the diastereomers=3.6 and 3.8 min. Anal. C35H42N2O6F2, C=67.40, H=6.85, N=4.23, F=5.86 (found) C=67.29, H=6.78, N=4.48, F=6.08 (calcd.).

Provenance & Evidence