Sodium Carbonate → (3R,4S)-3-amino-1-(2-aminoethyl)-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid

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) in anhydrous 1,2-dichloroethane (5 mL) was treated with anhydrous sodium sulfate (1 g) and N-bocaminoacetaldehyde (111 mg, 0.7 mmol), stirred for 3 h, then treated with sodium triacetoxyborohydride (212 mg, 1.0 mmol) and glacial acetic acid (2 drops) 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 saturated aqueous sodium chloride (20 mL each), dried (MgSO4), and concentrated. The crude material was deprotected and isolated using the method described for example 8, step 5 to afford (3R,4S)-3-amino-1-(2-aminoethyl)-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid (64 mg, 35%) as a yellow solid. NMR (D2O) δ 3.60-4.00 (m, 4 H), 3.15-3.50 (m, 4 H), 2.60 (m, 1 H), 1.40-1.65 (m, 1 H), 1.10-1.35 (m, 3 H), 0.63-0.73 (m, 2 H). MS (m+1): 260.2; MS (m−H2O+1): 242.3.

1. stirringstirred for 18 h
2. stirringthe mixture stirred for a few minutes
3. extractionextracted with ethyl acetate (30 mL
4. washThe combined organic solution was washed with water and saturated aqueous sodium chloride (20 mL each)
5. dry with materialdried (MgSO4)
6. concentrationconcentrated
7. customisolated

ORD-Eintrag

ord-2f29f5b36d374ec089bf8c2c0e331cb7

Quelldatensatz

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09440995B2