Diisopropylamine → 4-(4-But-2-ynyloxybenzenesulfonyl)-piperidine-1,4-dicarboxylic Acid tert-butyl Ester Methyl Ester

Temperatur

-78 °C

To a solution of diisopropylamine (1.58 mL, 11.3 mmol) in THF (25 mL) at 0° C. was added 2.5M n-BuLi(4.68 mL, 11.7 mmol) and the resulting mixture was stirred for 15 min at that temperature. The reaction mixture was cooled to −78° C. and a solution of 1-(tert-butyl)-4-methyl 1,4-piperidinecarboxylate (prepared from example 30, step 1) (2.67 g, 11.0 mmol) in THF (40 mL) was added. The resulting mixture was stirred for 1 h and a solution of 4-but-2-ynyloxy benzenesulfonyl fluoride (2.5 g, 11.0 mmol) in THF (25 mL) was added into it. After stirring for 4 h at rt, the reaction was quenched with satd. aqueous NH4Cl solution and extracted with EtOAc, dried over anhydrous Na2SO4. The crude product was purified by silica gel chromatography to obtain 2.6 g(53%) of the product as a solid; 1H NMR(300 MHz, CDCl3) δ1.44(s, 9H), 1.87(m, 3H), 1.98(m, 2H), 2.32(m, 2H), 2.62(m, 2H), 3.74(s, 3H), 4.17(m, 2H), 4.74(m, 2H), 7.09(d, 2H, J=7.2 Hz), 7.71(d, 2H, J=7.2 Hz).

1. stirringThe resulting mixture was stirred for 1 h
2. stirringAfter stirring for 4 h at rt
3. customthe reaction was quenched with satd
4. extractionaqueous NH4Cl solution and extracted with EtOAc
5. dry with materialdried over anhydrous Na2SO4
6. customThe crude product was purified by silica gel chromatography

ORD-Eintrag

ord-76fdcec4bcd34f0da3c3c05fb56e81c4

Quelldatensatz

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06358980B1