4-Methylmorpholine → Ethyl(5r/s,6r/s)-6-(hydroxymethyl)spiro[2.4]heptane-5-carboxylate

Temperature

-78 °C

trans-6-(Ethoxycarbonyl)spiro[2.4]heptane-5-carboxylic acid (165 mg, 832 mmol) was placed in a 25 mL round bottom flask. After flushing the flask with nitrogen, tetrahydrofuran (1.6 mL) was added and the reaction mixture was cooled to −78° C. 4-Methylmorpholine (0.11 mL, 1.0 mmol) and isobutyl chloroformate (0.12 mL, 0.93 mmol) were added and the reaction mixture was allowed to warm to ambient temperature. After 15 min., the reaction mixture was recooled to −78° C. and sodium borohydride (60 mg, 1.6 mmol) was added. Methanol (1.3 mL) was added and the reaction mixture was warmed to ambient temperature over 2 h and then quenched with saturated aqueous ammonium chloride. The reaction mixture was diluted with saturated aqueous sodium chloride solution and the product was extracted with ethyl acetate. The combined organics were dried over anhydrous sodium sulfate and then concentrated on a rotary evaporator. Chromatography of the residue on silica gel using 35:65 ethyl acetate:hexanes as eluent provided ethyl(5R/S,6R/S)-6-(hydroxymethyl)spiro[2.4]heptane-5-carboxylate as a colorless oil.

1. customAfter flushing the flask with nitrogen, tetrahydrofuran (1.6 mL)
2. additionwas added
3. temperatureto warm to ambient temperature
4. customwas recooled to −78° C.
5. temperaturethe reaction mixture was warmed to ambient temperature over 2 h
6. customquenched with saturated aqueous ammonium chloride
7. additionThe reaction mixture was diluted with saturated aqueous sodium chloride solution
8. extractionthe product was extracted with ethyl acetate
9. dry with materialThe combined organics were dried over anhydrous sodium sulfate
10. concentrationconcentrated on a rotary evaporator

ORD record

ord-c11fbb4865a24749b7e71d21d19bc51b

Source dataset

uspto-grants-2008_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07371747B2