Triethylamine → [(S)-3-(4-fluorobenzyl)-piperidin-1-yl]-[(3R,4S)-4-((R)-1-phenyl-ethylamino)-tetrahydrothiophen-3-yl]-methanone

A cloudy solution of (3R,4S)-4-[(R)-1-phenyl-ethylamino]-tetrahydrothiophene-3-carboxylic acid (containing sodium chloride; 928 mg, 2.54 mmol) in dichloromethane (20 mL) was treated with benzotriazol-1-yloxy-tripyrrolidinophosphonium hexafluorophosphate (1.59 g, 3.05 mmol) and triethylamine (814 μL, 5.84 mmol) and stirred for 5 minutes. A solution of the (S)-3-(4-fluorobenzyl)-piperidine prepared above in dichloromethane (5 mL) was added and the mixture was stirred at room temperature. After 21.5 h , the mixture was diluted with dichloromethane, washed with water and saturated NaHCO3, dried (Na2SO4) and concentrated. The residue was purified by flash column chromatography (55% ethyl acetate/hexanes) to provide the product as a gum (1.05 g, 94%). 1H NMR (300 mHz, CDCl3) δ7.32 (m, 4H), 7.27 (m, 1H), 7.10 (m, 2H), 6.99 (m, 2H), 4.47 (m, 1H), 3.9-3.6 (m, 3H), 3.2 (m, 1H), 2.95 (m, 2H), 2.8-2.4 (m, 6H), 1.9-1.6 (m, 4H), 1.4 (m, 1H), 1.37 (m, 3H), 1.2 (m, 1H), ESI MS: (M+H)+=427.4.

1. additionwas added
2. stirringthe mixture was stirred at room temperature
3. waitAfter 21.5 h
4. washwashed with water and saturated NaHCO3
5. dry with materialdried (Na2SO4)
6. concentrationconcentrated
7. customThe residue was purified by flash column chromatography (55% ethyl acetate/hexanes)

ORDレコード

ord-dbaee80b4ea7426682873c797c995d85

出典データセット

uspto-grants-2003_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06627629B2