Trifluoroacetic acid → (S)-3-Amino-1-(2-hydroxy-ethyl)-pyrrolidin-2-one

NaBH4 (85 mg, 2.24 mmol) was added to a solution of 40b (160 mg, 0.56 mmol) in ter-butyl alcohol (5 mL). The temperature was brought to 80° C., and MeOH (0.6 mL) was added slowly. The resulting mixture was kept under reflux for 2 h. After cooling under an ice bath, H2O (20 mL) was added and the alcohols were evaporated under vacuum. The aqueous phase was extracted with EA for several times. The organic layer was dried over anhydrous MgSO4 and concentrated. The residue was purified by Prep TLC to provide 41a (38 mg). To a solution of compound 41a (38 mg, 0.156 mmol) in 5 mL of DCM, was added TFA (0.18 mL, 2.34 mmol). The resulting mixture was stirred at r.t. for about 1 h and evaporated. The residue was added to a solution of A4 (36 mg, 0.086=101) and DIEA (0.08 mL, 0.43 mmol) in 20mL of DMF. The reaction Mixture was stirred at room temperature for several hours. LC/MS detection was applied to determine completion of the reaction. DMF was evaporated under reduced pressure and the residue was precipitated with 5% diethylamine/methanol (5 mL) The precipitate was collected by filtration, washed with ethanol and dried in vacuo to give an orange solid (29 mg, 79.2% yield): 1H NMR (300 MHz, DMSO-d6): δ=13.69 (s, 1H), 10.91 (s, 1H), 7.72-7.85 (m, 3H), 6.82-6.96 (m, 2H), 4.58-4.74 (m, 2H), 3.37-3.54 (m, 4H), 3.12-3.20 (m, 1H), 1.87-2.45 (m, 8H), 1.23-1.97 (m, 1H). LC/MS: 427.0 [M+H]+.

1. customevaporated
2. stirringThe reaction Mixture was stirred at room temperature for several hours
3. customcompletion of the reaction
4. customDMF was evaporated under reduced pressure
5. customthe residue was precipitated with 5% diethylamine/methanol (5 mL) The precipitate
6. filtrationwas collected by filtration
7. washwashed with ethanol
8. customdried in vacuo

ORD record

ord-328c3111fd414d749b3f27c437aad649

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08524709B2