Acetic Acid → (3R,4S)-3-amino-1-(2-aminocyclohexyl)-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid

Temperature

40 °C

A stirred solution of (3R,4S)-3-acetamido-N-tert-butyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-3-carboxamide (Example 8, step 4) (198 mg, 0.5 mmol) and 2-(N—BOC-amino)cyclohexane-1-one (0.213 g, 1.0 mmol) in anhydrous 1,2-dichloroethane (5 mL) was treated with anhydrous sodium sulfate (1 g) and glacial acetic acid (30 mg, 0.5 mmol), stirred at 40° C. for 1 h, then cooled to room temperature and treated with sodium triacetoxyborohydride (276 mg, 1.3 mmol) and stirred for 18 h. Aqueous sodium carbonate (10%, 5 mL) was added and the mixture stirred for a few minutes and extracted with ethyl acetate (30 mL, then 2×10 mL). The combined organic solution was washed with water and brine (20 mL each), dried (MgSO4), and concentrated in vacuo. The crude material was deprotected and isolated using the method described for example 8, step 5 to afford (3R,4S)-3-amino-1-(2-aminocyclohexyl)-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid (156 mg, 74%) as a white powder. NMR (D2O) δ 3.65-4.05 (m, 3 H), 3.05-3.60 (m, 3 H), 2.90-3.10 (m, 1 H), 1.95-2.10 (m, 2 H), 1.45-1.75 (m, 5 H), 1.15-1.40 (m, 5 H), 0.62-0.72 (m, 2 H). MS (m+1): 314.1; MS (m−H2O+1): 296.1.

1. temperaturecooled to room temperature
2. stirringstirred for 18 h
3. stirringthe mixture stirred for a few minutes
4. extractionextracted with ethyl acetate (30 mL
5. washThe combined organic solution was washed with water and brine (20 mL each)
6. dry with materialdried (MgSO4)
7. concentrationconcentrated in vacuo
8. customisolated

ORD record

ord-5576ae31feda4794adc4210d0c715df7

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09233985B2