Phosphinic Acid → (S)-5-tert-Butyl 6-methyl 5-azaspiro[2.4]heptane-5,6-dicarboxylate

Temperature

90 °C

To the solution of (6S)-5-tert-butyl 6-methyl 1,1-dibromo-5-azaspiro[2.4]heptane-5,6-dicarboxylate (69 mg, 0.167 mmol) in water (1 mL) and ACN (0.5 mL) were added the hypophosphorous acid (0.078 mL, 0.96 mmol), TEA (0.27 mL, 1.92 mmol) and V-50 (4.5 mg, 0.0167 mmol). The solution was degassed and was heated at 90° C. for 15 hours. After being cooled, the solution was diluted with H2O, extracted with EtOAc (×3) and was dried (Na2SO4), concentrated. The crude product was treated under the conditions above for another 15 hours. After cooled, the solution was diluted with H2O (10 mL) and tuned to pH 4 by adding aq HCl (4 N). The aqueous phase was extracted with EtOAc (×3), dried (Na2SO4). After concentrated under vacuum, the title compound was obtained as colorless oil (20 mg, 42%).

1. customThe solution was degassed
2. temperatureAfter being cooled
3. additionthe solution was diluted with H2O
4. extractionextracted with EtOAc (×3)
5. dry with materialwas dried (Na2SO4)
6. concentrationconcentrated
7. additionThe crude product was treated under the conditions above for another 15 hours
8. temperatureAfter cooled
9. additionthe solution was diluted with H2O (10 mL)
10. additionby adding aq HCl (4 N)
11. extractionThe aqueous phase was extracted with EtOAc (×3)
12. dry with materialdried (Na2SO4)
13. concentrationAfter concentrated under vacuum

ORD record

ord-4d66a287d1bb49f2a16dbd23d7dcae22

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08927739B2