Reaction #89640

Reaction equation

(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

N-boc-piperidine-4-carboxaldehyde

sodium triacetoxyborohydride

sodium carbonate

→

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

Yield 42.1%

Solvents

1,2-dichloroethane

Conditions

Workup

1. 1
   workup.STIRRINGstirred for 16 h
2. 2
   workup.STIRRINGthe mixture stirred for a few minutes
3. 3
   Extractionextracted with ethyl acetate (30 mL
4. 4
   WashThe combined organic solution was washed with water and saturated aqueous sodium chloride (20 mL each)
5. 5
   Dryingdried (MgSO4)
6. 6
   Concentrationconcentrated
7. 7
   Otherisolated

Procedure

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-boc-piperidine-4-carboxaldehyde (149 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 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-(piperidin-4-ylmethyl)pyrrolidine-3-carboxylic acid (66 mg, 31%) as a granular amber solid. NMR (D2O) δ 3.70-4.00 (m, 2 H), 3.30-3.45 (m, 4 H), 3.25 (d, J=7 Hz, 2 H), 2.92 (br t, J=13 Hz, 2 H), 2.50-2.65 (m, 1 H), 2.00-2.15 (m, 1 H), 1.85-2.00 (m, 2 H), 1.50-1.65 (m, 1 H), 1.35-1.50 (m, 2 H), 1.15-1.35 (m, 3 H), 0.65-0.75 (m, 2 H). MS (m−H2O+1): 296.3; MS (m−2 H2O+1): 278.1.

Source