Réaction #89654

Équation de réaction

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

4-carbethoxycyclohexanone

sodium sulfate

acetic acid

sodium carbonate

sodium triacetoxyborohydride

→

(3R,4S)-3-amino-4-(3-boronopropyl)-1-(4-carboxycyclohexyl)pyrrolidine-3-carboxylic acid

Rendement 78.9%

Solvants

1,2-dichloroethane

Conditions de réaction

Traitement

1. 1
   Températurecooled to room temperature
2. 2
   workup.STIRRINGstirred for 18 h
3. 3
   workup.STIRRINGthe mixture stirred for a few minutes
4. 4
   Extractionextracted with ethyl acetate (30 mL
5. 5
   LavageThe combined organic solution was washed with water and saturated aqueous sodium chloride (20 mL each)
6. 6
   Séchagedried (MgSO4)
7. 7
   Concentrationconcentrated
8. 8
   Autreisolated

Mode opératoire

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 4-carbethoxycyclohexanone (0.170 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 3 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 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-4-(3-boronopropyl)-1-(4-carboxycyclohexyl)pyrrolidine-3-carboxylic acid (135 mg, 65%) as a white solid. NMR (D2O) δ 3.97 (dd, J1=13 Hz, J2=7 Hz, 1 H), 3.75-3.90 (m, 2 H), 3.15-3.35 (m, 2 H), 2.20-2.70 (m, 2 H), 1.90-2.20 (m, 4 H), 1.50-1.65 (m, 3 H), 1.15-1.45 (m, 5 H), 0.60-0.70 (m, 2 H). MS (m+1): 343.1; MS (m−H2O+1): 325.0.

Source