1,2-Dichloroethane → tert-Butyl 6-carbamoyl-3-azabicyclo[3.1.0]hexane-3-carboxylate

To a solution of 1 (6.65 g, 26.2 mmol) in THF (100 mL) and MeOH (40 mL) was added a solution of LiOH (4.40 g, 104 mmol) in H2O (40 mL) and stirred for 2 h. The reaction was quenched upon addition of 0.5 N HCl (150 mL) and extracted with EtOAc (2×200 ml). The combined organic extracts were dried over MgSO4 and concentrated under vacuum to afford the intermediate acid. Dissolved in DMF (90 mL), added DIPEA (18.8 mL, 104 mmol), EDC (5.84 g, 31.4 mmol), HOBt (4.24 g, 31.4 mmol) and NH4Cl (4.16 g, 78.5 mmol). The reaction was sealed and stirred for 48 h. Diluted the reaction with water (350 mL) and extracted with EtOAc (2×250 mL). The combined organic extracts were washed with water (2×300 mL), brine (300 mL), dried over MgSO4 and concentrated under vacuum to afford 2 (1.84 g, 31%) as a white solid; 1H-nmr (400 MHz, CDCl3) δ 5.75 (s, 1H), 5.45 (s, 1H), 3.68 (d, J=7.0 Hz, 1H), 3.58 (d, J=11.0 Hz, 1H), 3.43 (d, J=11.0 Hz, 2H), 2.07 (s, 2H), 1.44 (s, 9H), 1.31-1.26 (m, 1H); LC-MS (214 nM) 2.15 min (>98%), m/z 171 [M-tBu].

1. customThe reaction was quenched upon addition of 0.5 N HCl (150 mL)
2. extractionextracted with EtOAc (2×200 ml)
3. dry with materialThe combined organic extracts were dried over MgSO4
4. concentrationconcentrated under vacuum
5. customto afford the intermediate acid
6. customThe reaction was sealed
7. stirringstirred for 48 h
8. additionDiluted
9. extractionextracted with EtOAc (2×250 mL)
10. washThe combined organic extracts were washed with water (2×300 mL), brine (300 mL)
11. dry with materialdried over MgSO4
12. concentrationconcentrated under vacuum

ORDレコード

ord-a8cafb4f00bb49a6b47afd19832a66de

出典データセット

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08497289B2