Reaktion #89649

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

ethyl 5-bromonicotinate

rac-binap

cesium carbonate

→

5-((3R,4S)-3-amino-4-(3-boronopropyl)-3-carboxypyrrolidin-1-yl)nicotinic acid

Ausbeute 48.6%

Lösungsmittel

toluene

methylene chloride

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturcooled to room temperature
2. 2
   Filtrationfiltered through Celite®
3. 3
   Einengenthe filtrate concentrated
4. 4
   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) and ethyl 5-bromonicotinate (138 mg, 0.60 mmol) in anhydrous toluene (2.5 mL) was degassed under nitrogen for 15 min, then treated with palladium diacetate (14 mg, 0.06 mmol), rac-binap (75 mg, 0.12 mmol), and cesium carbonate (0.65 g, 2 mmol). The mixture was heated to 80° C. for 18 h, cooled to room temperature, diluted with methylene chloride (20 mL), filtered through Celite® and the filtrate concentrated. The crude material was deprotected and isolated using the method described for example 8, step 5 to afford 5-((3R,4S)-3-amino-4-(3-boronopropyl)-3-carboxypyrrolidin-1-yl)nicotinic acid (82 mg, 40%) as a yellow solid. NMR (D2O) δ 8.37 (s, 1 H), 8.00 (s, 2 H), 3.99 (d, J=11 Hz, 1H), 3.88 (t, J=10 Hz, 1 H), 3.68 (d, J=11 Hz, 1 H), 3.26 (t, J=10 Hz, 1 H), 2.60-2.75 (m, 1 H), 1.60 (m, 1 H), 1.20-1.50 (m, 3 H), 0.65-0.75 (m, 2 H). MS (m+1): 338.2; MS (m−H2O+1): 320.1.

Quelle