Diiodomethane → (1S,3S,5S)-2-Tert-butyl 3-ethyl 2-azabicyclo[3.1.0]hexane-2,3-dicarboxylate

Temperature

0 °C

At 0° C. a solution of TFA (104 mmol, 2.0 eq) in DCM (50 mL) is added dropwise to a solution of diethylzinc (104 mmol, 2.0 eq) in hexane (104 mL) and DCM (100 mL). After 30 min a solution of diiodomethane (104 mmol, 2.0 eq) in DCM (50 mL) is added slowly to the white suspension. The mixture is stirred for 10 min and treated with a solution of (S)-2,3-dihydro-pyrrole-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester (52 mmol, 1.0 eq) in DCM (50 mL). After 5 min the mixture is allowed to reach RT, stirred for additional 2.5 h, cooled to 0° C. and treated slowly with TEA (18 mL). After 14 h a sat. aqueous NaHCO3 solution is added and the mixture is filtered through Celite. The residue is washed with DCM (100 mL) and the layers are separated. The organic layer is washed twice with water, dried over Na2SO4 and concentrated in vacuo. The residue is purified by flash chromatography (heptane/EtOAc 9/1) to give the desired product as a pale yellow oil. LC-MS (basic): tR=0.90 min; [M+H]+=256.3.

1. waitAfter 5 min the mixture is allowed
2. customto reach RT
3. stirringstirred for additional 2.5 h
4. filtrationthe mixture is filtered through Celite
5. washThe residue is washed with DCM (100 mL)
6. customthe layers are separated
7. washThe organic layer is washed twice with water
8. dry with materialdried over Na2SO4
9. concentrationconcentrated in vacuo
10. customThe residue is purified by flash chromatography (heptane/EtOAc 9/1)

ORD record

ord-9383804d62074fde804c1ba62710993e

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08288435B2