Dimethyl Sulfoxide → HCID 20641344, compound

Participants

Reaction Steps

To a solution of oxalyl chloride (0.31 mL, 3.58 mmol) in CH2Cl2 (22 mL) at −78° was added dropwise a solution of DMSO (0.48 mL, 6.83 mmol) in CH2Cl2 (1.4 mL). After 15 min, a solution of 1-(tert-butyldimethylsilyl)-4(R)-(hydroxymethyl)azetidin-2-one (700 mg, 3.25 mmol) in CH2Cl2 (3.3 mL) was added and the reaction was stirred an extra 45 min. Finally, DIEA (2.8 mL, 16.25 mmol) was added and the reaction was stirred at room temperature for 2 h. The resulting mixture was diluted with H2O and extracted with CH2Cl2. The organic phase was washed with aqueous HCl (10%), saturated NaHCO3 and brine, dried (MgSO4), filtered and concentrated. The crude aldehyde was immediately used in the next step. To the crude aldehyde dissolved in THF (29 mL) was added dropwise MeMgBr (3M/Et2O, 2.7 mL, 8.18 mmol) The reaction mixture was stirred 1 h at 0° and 1 h at room temperature, followed by the addition of aqueous saturated NH4Cl solution. After extraction with EtOAc, the organic phase was washed with HCl (10%), saturated aqueous NaHCO3 and brine, dried (MgSO4), filtered and evaporated. The resulting mixture was purified by flash chromatography (SiO2, 40% EtOAc-hexane) to give 1-(tert-butyldimethylsilyl)-4(R)-(1-hydroxyethyl)azetidin-2-one (580 mg, 77% yield for two steps) as a mixture of isomers. 1H NMR (400 MHz, CDCl3) δ 4.02-3.96 (m, 1H), 3.81 (q, J=6.5 Hz, 1H), 4.33-4.27 (m, 1H), 3.50-3.43 (m,2H), 3.01 (dd, J=15.6, 5.6 Hz, 1H), 2.95 (dd, J=15.3, 2.9 Hz, 1H), 2.84 (dd, J=15.1, 5.6 Hz, 1H), 2.58 (dd, J=15.6, 2.9 Hz, 1H), 1.14 (d, J=6.4 Hz, 3H), 1.07 (d, J=6.7 Hz, 3H), 0.92-0,91 (m, 18H), 0.22-0.11 (m, 6H)

Provenance & Evidence