Acetic Acid → (3R,4S)-3-amino-4-(3-boronopropyl)-1-(piperidin-3-yl)pyrrolidine-3-carboxylic acid

HRID 590718노트

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HRID 590718 반응식
C([NH:4][C@:5]1([C:22](NC(C)(C)C)=[O:23])[C@@H:9]([CH2:10][CH2:11][CH2:12][B:13]2[O:17]C(C)(C)C(C)(C)[O:14]2)[CH2:8][NH:7][CH2:6]1)(=O)C.C([N:36]1[CH2:41][CH2:40][CH2:39][C:38](=O)[CH2:37]1)(OC(C)(C)C)=O.S([O-])([O-])(=O)=[O:44].[Na+].[Na+].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>ClCCCl>[NH2:4][C@:5]1([C:22]([OH:23])=[O:44])[C@@H:9]([CH2:10][CH2:11][CH2:12][B:13]([OH:14])[OH:17])[CH2:8][N:7]([CH:38]2[CH2:39][CH2:40][CH2:41][NH:36][CH2:37]2)[CH2:6]1

참가 물질

8

반응물 6

HCID 176Acetic AcidHCID 10340Sodium CarbonateHCID 24436Sodium SulfateHCID 2756825Tert-butyl 3-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 67516451(3R,4S)-3-acetamido-N-tert-butyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-3-carboxamide

생성물 1

HCID 57331441(3R,4S)-3-amino-4-(3-boronopropyl)-1-(piperidin-3-yl)pyrrolidine-3-carboxylic acid수율 92.3%

시약·촉매·용매 1

HCID 111,2-Dichloroethane용매

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온도
40 °C

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) and N—BOC-piperidine-3-one (0.199 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-(piperidin-3-yl)pyrrolidine-3-carboxylic acid (138 mg, 68%) as an amber solid. NMR (D2O) δ 3.80-4.10 (m, 2 H), 3.60-3.80 (m, 2 H), 3.30-3.50 (m, 2 H), 3.00-3.15 (m, 1 H), 2.80-2.95 (m, 1 H), 2.45-2.60 (m, 1 H), 2.30 (m, 1 H), 1.95-2.10 (m, 1 H), 1.50-1.85 (m, 4 H), 1.10-1.40 (m, 3 H), 0.60-0.70 (m, 2 H). MS (m+1): 300.1; MS (m−H2O+1): 282.1.

후처리

  1. temperaturecooled to room temperature
  2. stirringstirred for 18 h
  3. stirringthe mixture stirred for a few minutes
  4. extractionextracted with ethyl acetate (30 mL
  5. washThe combined organic solution was washed with water and saturated aqueous sodium chloride (20 mL each)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customisolated

출처 및 근거

ORD 기록
ord-6c25cff544d84bda97ccc687f7246a05
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09233985B2

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