Methyl morpholine oxide → HCID 55298156, compound

A solution of 4-(benzyloxy)-2-(2-chloroethyl)tetrahydrofuran (2.47 g, 10.26 mmol) in ethyl acetate (50 mL) was deoxygenated for 5 min by bubbling N2 through. 10% Pd/C (0.145 g, 1.363 mmol) was added the flask evacuated then placed under 1 atm H2 for 4 h. The reaction was filtered and concentrated to give a colorless oil (1.74 g) which was used in the next step without purification. A solution of 4-methylmorpholine N-oxide (1.803 g, 15.39 mmol) in CH2Cl2 (50 mL), intermediate 5-(2-chloroethyl)tetrahydrofuran-3-ol and 4 Å powdered molecular sieves (4 g) was stirred for 30 min. To this mixture was added tetrapropylammonium perruthenate (0.036 g, 0.103 mmol) and stirring continued for 24 h at room temperature. The reaction was concentrated, then diluted with Et2O (100 mL) and filtered through a plug of CELITE®. The filtrate was concentrated to afford 5-(2-chloroethyl)dihydrofuran-3(2H)-one as viscous colorless oil. To a stirred mixture of 5-(2-chloroethyl)dihydrofuran-3(2H)-one, aqueous ammonia (5 mL) and 1N HCl (10 mL) in methanol 20 mL was added NaCN (0.43 g, 8.77 mmol) at room temperature. The yellow solution was stirred for 42 h and concentrated. The solution was made basic with sat. Na2CO3 (20 mL) and extracted with CH2Cl2 (3×25 mL). To the combined CH2Cl2 extracts was added sat. Na2CO3 (10 mL), and the mixture cooled to 0° C. with an ice bath and treated with benzyl chloroformate (1.465 mL, 10.26 mmol). After 1 h, the ice bath was removed and the reaction was stirred at room temperature for 4 h. The organic layer was separated, dried (Na2SO4), filtered, concentrated and purified by flash column chromatography on silica gel column using 10, 20, 30 and 40% ethyl acetate/hexane to afford the title compound benzyl 5-(2-chloroethyl)-3-cyanotetrahydrofuran-3-ylcarbamate (0.863 g, 2.80 mmol, 27% yield), viscous pale yellow oil. 1H NMR (500 MHz, CDCl3) δ: 7.12-7.42 (5 H, m), 5.16 (2 H, s), 4.40 (0.2 H, d, J=9.8 Hz), 4.25-4.33 (0.8 H, m), 4.10-4.19 (1 H, m), 3.95 (0.2 H, d, J=9.8 Hz), 3.56-3.68 (1.8 H, m), 2.86 (1 H, dd, J=13.4, 7.0 Hz), 2.53-2.62 (1 H, m), 2.27 (1 H, dd, J=13.4, 8.9 Hz), 1.94-2.17 (2 H, m). LCMS (M+H) calcd for C15H18ClN2O3: 309.10; found: 309.10.

1. customwas used in the next step without purification
2. stirringstirring
3. waitcontinued for 24 h at room temperature
4. concentrationThe reaction was concentrated
5. additiondiluted with Et2O (100 mL)
6. filtrationfiltered through a plug of CELITE®
7. concentrationThe filtrate was concentrated

ORD record

ord-0e7d027e85a342e3879e47bf82177ce9

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08129398B2