Propanoic acid, 2-bromo-2-methyl-, ethyl ester → HCID 59253182, compound

A solution of 5.41 g (0.02 mmol) of 4-acetylsulfanyl-piperidine-1-carboxylic acid tert-butyl ester in ethanol (50 mL) is degassed with nitrogen over 0.5 h and 2.34 g (0.04 mol) of KOH are added, followed by 8.14 g (0.04 mol) of ethyl α-bromoisobutyrate. The reaction is stirred for 18 h at room temperature under a nitrogen atmosphere. The reaction mixture is concentrated under reduced pressure. The residue is partitioned between DCM (100 mL) and water (100 mL). The organic layer is washed with water (50 mL), brine (250 mL), dried over Na2SO4 and filtered. The filtrate is concentrated under reduced pressure and purified by column chromatography (silica, eluent heptanes, 50% ethyl acetate) to afford 6.05 g of 4-(1-ethoxycarbonyl-1-methyl-ethylsulfanyl)-piperidine-1-carboxylic acid tert-butyl ester as a brown oil. Yield: 87%; ES-MS: m/z 354 [M+Na], 232 [M+H—C5H9O2]; 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 1.25-1.35 (3 H, m), 1.46 (9 H, s), 1.48-1.53 (2 H, m), 1.55 (6 H, s), 1.88 (2 H, dd, J=13.31, 3.47 Hz), 2.94-3.04 (3 H, m), 3.81-3.92 (2 H, m), 4.19 (2 H, q, J=7.10 Hz)

1. concentrationThe reaction mixture is concentrated under reduced pressure
2. customThe residue is partitioned between DCM (100 mL) and water (100 mL)
3. washThe organic layer is washed with water (50 mL), brine (250 mL)
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationThe filtrate is concentrated under reduced pressure
7. custompurified by column chromatography (silica, eluent heptanes, 50% ethyl acetate)

ORD record

ord-f5aa8460bb414ab29bb92769823049dc

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08349871B2