Reaktion #89644

Reaktionsgleichung

(3R,4S)-3-acetamido-N-tert-butyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-3-carboxamide

sodium sulfate

imidazole-4-carboxaldehyde

sodium triacetoxyborohydride

sodium carbonate

→

(3R,4S)-1-((1H-imidazol-4-yl)methyl)-3-amino-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid

Ausbeute 25.7%

Lösungsmittel

1,2-dichloroethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGstirred for 16 h
2. 2
   workup.STIRRINGthe mixture stirred for a few minutes
3. 3
   Extraktionextracted with ethyl acetate (30 mL
4. 4
   WaschenThe combined organic solution was washed with water
5. 5
   Einengensaturate aqueous sodium chloride (20 mL each)
6. 6
   Trocknendried (MgSO4)
7. 7
   Einengenconcentrated
8. 8
   Sonstigeisolated

Vorschrift

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 imidazole-4-carboxaldehyde (110 mg, 0.7 mmol), stirred for 2 h, then treated with sodium triacetoxyborohydride (212 mg, 1.0 mmol) and glacial acetic acid (2 drops) and stirred for 16 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 saturate 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)-1-((1H-imidazol-4-yl)methyl)-3-amino-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid (38 mg, 21%) as a pale yellow granular solid. NMR (D2O) 8.74 (s, 1 H), 7.71 (s, 1 H), 4.60-4.80 (m, 2 H), 3.96 (d, J=12.5 Hz, 1H), 3.80 (dd, J1=11 Hz, J2=8 Hz, 1 H), 3.71 (d, J=12.5 Hz, 1 H), 3.40 (t, J=11.5 Hz, 1 H), 2.50-2.65 (m, 1 H), 1.50-1.65 (m, 1 H), 1.15-1.35 (m, 3 H), 0.60-0.70 (m, 2 H). MS (m−H2O+1): 279.0; MS (m−2 H2O+1): 261.3.

Quelle