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

Temperature

-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 hand a solution of 4-but-2-ynyloxy benzenesulfonyl fluoride (2.5 g, 11.0 mmol) in THF (25 mL) was added into it. After sting 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, 2), 4.74 (m, 2H), 7.09 (d, 2H, J=7.2 Hz), 7.71 (d, 2H, J=7.2 Hz).

1. additionwas added into it
2. waitAfter sting 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 record

ord-fe96f968373249428a8455c8b487bf06

Source dataset

uspto-grants-2004_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06753337B2