تفاعل #89660

معادلة التفاعل

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

N-BOC-piperidine-2-carboxaldehyde

sodium sulfate

acetic acid

sodium carbonate

sodium triacetoxyborohydride

→

(3R,4S)-3-amino-4-(3-boronopropyl)-1-(pyrrolidin-2-ylmethyl)pyrrolidine-3-carboxylic acid

المردود 96.3%

المذيبات

1,2-dichloroethane

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةcooled to room temperature
2. 2
   workup.STIRRINGstirred for 18 h
3. 3
   workup.STIRRINGthe mixture stirred for a few minutes
4. 4
   استخلاصextracted with ethyl acetate (30 mL
5. 5
   غسيلThe combined organic solution was washed with water and brine (20 mL each)
6. 6
   تجفيفdried (MgSO4)
7. 7
   تركيزconcentrated in vacuo
8. 8
   أخرىisolated

الإجراء التجريبي

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 N-BOC-piperidine-2-carboxaldehyde (0.15 g, 0.75 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 room temperature for 3 h, then cooled to room temperature and treated with sodium triacetoxyborohydride (212 mg, 1.0 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 brine (20 mL each), dried (MgSO4), and concentrated in vacuo. 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-(pyrrolidin-2-ylmethyl)pyrrolidine-3-carboxylic acid (144 mg, 70%) as a white foam. NMR (D2O) δ 3.85-4.05 (m, 3 H), 3.60-3.80 (m, 3 H), 3.40 (m, 1 H), 3.30 (m, 2 H), 2.55-2.70 (m, 1 H), 2.20-2.35 (m, 1 H), 1.85-2.10 (m, 2 H), 1.75 (m, 1 H), 1.60 (m, 1 H), 1.15-1.40 (m, 3 H), 0.63-0.73 (m, 2 H). MS (m+1): 300.1; MS (m−H2O+1): 282.1.

المصدر