Lithium diisopropylamide → 3-Cyclopentyl-2-[4-(4-methyl-piperazine-1-sulfonyl)phenyl]propionic acid ethyl ester

温度

-78 °C

A solution of the title C compound, [4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-acetic acid ethyl ester (15 g, 0.046 mol) in a mixture of THF (60 mL) and DMTP (10 mL) is cooled to −78° C. under nitrogen. The resulting solution is stirred at −78° C. for 45 min and to this is added LDA (25.6 mL, 6.40 g, 0.059 mol, 25% solution in THF/Hexane). A solution of iodomethylcyclopentane (11.60 g, 0.055 mol) in a mixture of DMTP (12 mL) and THF (20 mL) is added over a period of 15 min at −78° C. and reaction mixture stirred at −78° C. for 3 h further, followed by stirring at 25° C. for 12 h. The reaction mixture is then quenched by the dropwise addition of saturated aqueous ammonium chloride solution (50 mL) and is concentrated in vacuo. The residue is diluted with water (50 mL) and extracted with ethyl acetate (3×100 mL). The organic solution is washed with a saturated aqueous sodium chloride (2×150 mL), dried over sodium sulfate, filtered and concentrated in vacuo. Column chromatography over silica gel (60-120 mesh), using 50% ethyl acetate in hexane as an eluent to afford 3-cyclopentyl-2-[4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-propionic acid ethyl ester as a white solid: 1H NMR (400 MHz, CDCl3) δ 0.9-2.1 (m, 11H), 1.2 (t, J=7.1, 3H), 2.3 (s, 3H), 2.5 (br s, 4H), 3.0 (br s, 4H), 3.6 (m, 1H), 4.1 (q, J=7.1, 2H), 7.5 (d, J=8.3, 2H), 7.7 (d, J=8.3, 2H); MS 409 [M+1]+.

1. additionis added over a period of 15 min at −78° C.
2. customreaction mixture
3. stirringstirred at −78° C. for 3 h further
4. stirringby stirring at 25° C. for 12 h
5. customThe reaction mixture is then quenched by the dropwise addition of saturated aqueous ammonium chloride solution (50 mL)
6. concentrationis concentrated in vacuo
7. additionThe residue is diluted with water (50 mL)
8. extractionextracted with ethyl acetate (3×100 mL)
9. washThe organic solution is washed with a saturated aqueous sodium chloride (2×150 mL)
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated in vacuo

ORDレコード

ord-0ed93869943b407d8e19809bdf691d26

出典データセット

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07750020B2