Sodium Carbonate → HCID 57331397, Verbindung

HRID 61364Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 61364
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.S([O-])([O-])(=O)=O.[Na+].[Na+].C([N:43]1[CH2:48][CH2:47][CH2:46][CH:45]([CH:49]=O)[CH2:44]1)(OC(C)(C)C)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=[O:53])C.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>ClCCCl.C(O)(=O)C>[NH2:4][C@:5]1([C:22]([OH:23])=[O:53])[C@@H:9]([CH2:10][CH2:11][CH2:12][B:13]([OH:14])[OH:17])[CH2:8][N:7]([CH2:49][CH:45]2[CH2:46][CH2:47][CH2:48][NH:43][CH2:44]2)[CH2:6]1

Komponenten

8

Edukt 5

HCID 10340Sodium CarbonateHCID 24436Sodium SulfateHCID 5049666Sodium triacetoxyborohydrideHCID 99644481-Boc-piperidine-3-carboxaldehydeHCID 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

Produkt 1

HCID 57331397HCID 57331397, VerbindungAusbeute 39,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidKatalysatorHCID 111,2-DichloroethaneLösungsmittel

Versuchsvorschrift

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-3-carboxaldehyde (145 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-3-ylmethyl)pyrrolidine-3-carboxylic acid (62 mg, 29%) as a granular pale amber solid. NMR (D2O) δ 3.70-4.00 (m, 2 H), 3.20-3.45 (m, 5 H), 2.65-2.90 (m, 2 H), 2.50-2.65 (m, 2 H), 2.15-2.30 (m, 1 H), 1.75-2.00 (m, 2 H), 1.50-1.75 (m, 2 H), 1.10-1.40 (m, 4 H), 0.65-0.75 (m, 2 H). MS (m−H2O+1): 296.3; MS (m−2 H2O+1): 278.1.

Aufarbeitung

  1. stirringstirred for 16 h
  2. stirringthe mixture stirred for a few minutes
  3. extractionextracted with ethyl acetate (30 mL
  4. washThe combined organic solution was washed with water and saturated aqueous sodium chloride (20 mL each)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customisolated

Quellen und Nachweise

ORD-Eintrag
ord-d56a12cf7ebb478f8ffe34b8cb7555eb
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09440995B2

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