(Dimethyl sulfide)trihydroboron → Ethyl 5-oxa-6-azaspiro[3.4]octane-7-carboxylate

To a solution of crude 5-oxa-6-aza-spiro[3.4]oct-6-ene-7-carboxylic acid ethyl ester (7.5 g, <40.9 mmol) in tetrahydrofuran (270 mL) at 0° C. was slowly added a solution of borane-dimethyl sulfide complex (10 M in THF, 16.4 mL, 164 mmol). The reaction was allowed to warm to room temperature overnight then recooled to 0° C., and quenched by the careful addition of water. The mixture was diluted with ethyl acetate, washed with water and brine, dried (MgSO4), and concentrated to yield a large amount of white solids. These solids were thoroughly triturated three times with dichloromethane (150 mL). The combined dichloromethane washings were concentrated and the resulting oil was purified by flash chromatography to yield 5-oxa-6-aza-spiro[3.4]octane-7-carboxylic acid ethyl ester (1.08 g, 29% over 2 steps). 1H-NMR: 400 MHz, (CDCl3) δ: 8.01-7.95 (br, 1H), 4.39-4.28 (m, 2H), 4.18-4.10 (m, 1H), 2.80-2.75 (m, 1H), 2.62-2.49 (m, 2H), 2.37-2.29 (m, 1H), 2.25-2.17 (m, 1H), 2.13-1.95 (m, 1H), 1.88-1.79 (m, 1H), 1.68-1.56 (m, 1H), 1.34 (t, J=7.1 Hz, 3H) ppm.

1. customthen recooled to 0° C.
2. customquenched by the careful addition of water
3. additionThe mixture was diluted with ethyl acetate
4. washwashed with water and brine
5. dry with materialdried (MgSO4)
6. concentrationconcentrated
7. customto yield a large amount of white solids
8. customThese solids were thoroughly triturated three times with dichloromethane (150 mL)
9. concentrationThe combined dichloromethane washings were concentrated
10. customthe resulting oil was purified by flash chromatography

ORDレコード

ord-1d532bace8a64ce49db4c847de4d6ada

出典データセット

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08841278B2