Dimethyl Sulfoxide → Tert-butyl (S)-4-benzyl-2-(2-oxoethyl)piperazine-1-carboxylate

Temperature

-78 °C

Add dichloromethane (3 mL) to a 50 mL dry schlenk flask, followed by oxalyl chloride (0.178 g, 1.4 mmol) and cool the solution to −78° C. and treat with dimethyl sulfoxide (0.171 g, 2.2 mmol) and triethylamine (0.505 g, 5.0 mmol). After 10 min, add a solution of (S)-4-benzyl-2-(2-hydroxy-ethyl)-piperazine-1-carboxylic acid tert-butyl ester (0.320 g, 1.0 mmol) in dichloromethane (5 mL) and stir the resulting mixture at −78° C. for 1 hour. Quench the reaction mixture by adding sat. NaHCO3, extract the aqueous solution with CH2Cl2, wash the organic solvent with brine, and dry over Na2SO4. Purification by silica gel chromatography of the crude product using MeOH/CH2Cl2 (5% to 10%) as eluent to give the title compound (160 g, 50%) as a light yellow oil: mass spectrum (Electrospray): m/z=319.2 (M+1); 1H NMR (400 MHz, CDCl3): δ9.74 (t, 1H, J=2.0 Hz), 7.33–7.21 (m, 5H), 4.57 (br, 1H), 3.88 (m, 2H), 33.52–3.40 (m, 21H), 3.15–3.05 (m, 1H), 2.83–2.66 (m, 4H), 2.22–2.18 (m, 1H), 2.03 (dt, 1H, J=3.4, 11.8 Hz), 1.44 (s, 9H).

1. customdry schlenk flask
2. customQuench the reaction mixture
3. additionby adding sat. NaHCO3
4. extractionextract the aqueous solution with CH2Cl2
5. washwash the organic solvent with brine
6. dry with materialdry over Na2SO4
7. customPurification by silica gel chromatography of the crude product

ORD record

ord-1183eca1e04842d289e21c2eb70854a9

Source dataset

uspto-grants-2007_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07214673B2