1-O-tert-butyl 2-O-ethyl (2S)-2,3-dihydropyrrole-1,2-dicarboxylate

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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. After 5 min the mixture is allowed to reach RT stirred for additional 2.5 h the mixture is filtered through Celite The residue is washed with DCM (100 mL) the layers are separated The organic layer is washed twice with water dried over Na2SO4 concentrated in vacuo The residue is purified by flash chromatography (heptane/EtOAc 9/1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At −50° C. a solution of lithium triethylborohydride in THF (1.0 M, 107 mL, 1.07 eq) is added dropwise to a solution of (S)-5-oxo-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester (100 mmol, 1.0 eq) in toluene (170 mL). After 45 min DIPEA (450 mmol, 4.5 eq) and powdered DMAP (1.31 mmol) are added slowly at −50° C. The mixture is treated with trifluoroacetic anhydride (120 mmol, 1.20 eq) while keeping the internal temperature below −45° C., allowed to reach RT within 90 min and stirred for additional 17 h. At 0° C. water (250 mL) is added slowly and the layers are separated. The organic layer is washed with ice-cold water (3×250 mL) and concentrated in vacuo to give the desired product as an orange liquid. LC-MS (acidic): tR=0.93 min; [M+H]+=242.2. the internal temperature below −45° C. the layers are separated The organic layer is washed with ice-cold water (3×250 mL) concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: POCl3 (7.59 mL, 83 mmol) was added in 25 min at 0° C. under N2 atmosphere to DMF (6.39 mL, 83 mmol) and the mixture was stirred at RT for 20 min. Dry CH2Cl2 (150 mL) was added at 0° C., followed by a solution of (S)-2,3-dihydro-pyrrole-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester (10 g, 41.4 mmol) in CH2Cl2 (50 mL). The mixture was stirred 30 min at RT until completion. The mixture was slowly poured into an ice cold aqueous solution of NaOH 10 N (150 mL) and extracted with CH2Cl2 (×3). The combined organic extracts were washed with brine (×2), with water, dried (Na2SO4), filtered and concentrated. The crude residue was purified by flash column chromatography on silica gel (c-hexane to c-hexane/EtOAc 9:1) to give the desired material as a yellow oil. Rf, TLC (c-hexane/EtOAc 4:1)=0.2; MS (UPLC-MS): 270 [M+H]+, 170 [M−Boc]−; tR (HPLC conditions f): 1.93 min. The mixture was stirred 30 min at RT until completion extracted with CH2Cl2 (×3) The combined organic extracts were washed with brine (×2), with water dried (Na2SO4) filtered concentrated The crude residue was purified by flash column chromatography on silica gel (c-hexane to c-hexane/EtOAc 9:1)