Reacción #542467

Ecuación de reacción

DIPEA

EDC

HOBt

NH4Cl

1

3-tert-butyl 6-ethyl 3-azabicyclo[3.1.0]hexane-3,6-dicarboxylate

LiOH

→

2

Rendimiento 31.0%

3-tert-butyl 6-carbamoyl-3-azabicyclo[3.1.0]hexane-3-carboxylate

Rendimiento 31.0%

Disolventes

water

DMF

THF

MeOH

H2O

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe reaction was quenched upon addition of 0.5 N HCl (150 mL)
2. 2
   Extracciónextracted with EtOAc (2×200 ml)
3. 3
   SecadoThe combined organic extracts were dried over MgSO4
4. 4
   Concentraciónconcentrated under vacuum
5. 5
   Otroto afford the intermediate acid
6. 6
   OtroThe reaction was sealed
7. 7
   workup.STIRRINGstirred for 48 h
8. 8
   workup.ADDITIONDiluted
9. 9
   Extracciónextracted with EtOAc (2×250 mL)
10. 10
    LavadoThe combined organic extracts were washed with water (2×300 mL), brine (300 mL)
11. 11
    Secadodried over MgSO4
12. 12
    Concentraciónconcentrated under vacuum

Procedimiento

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].

Fuente