반응 #89644

반응 방정식

(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

수율 25.7%

용매

1,2-dichloroethane

반응 조건

후처리

1. 1
   workup.STIRRINGstirred for 16 h
2. 2
   workup.STIRRINGthe mixture stirred for a few minutes
3. 3
   추출extracted with ethyl acetate (30 mL
4. 4
   세척The combined organic solution was washed with water
5. 5
   농축saturate aqueous sodium chloride (20 mL each)
6. 6
   건조dried (MgSO4)
7. 7
   농축concentrated
8. 8
   기타isolated

실험 절차

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.

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