Acetic Acid → (3R,4S)-3-amino-4-(3-boronopropyl)-1-((1-methyl-1H-imidazol-2-yl)methyl)pyrrolidine-3-carboxylic acid

HRID 61377

Reaction equation

HRID 61377 reaction equation
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.[CH3:29][N:30]1[CH:34]=[CH:33][N:32]=[C:31]1[CH:35]=O.S([O-])([O-])(=O)=[O:38].[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:38])[C@@H:9]([CH2:10][CH2:11][CH2:12][B:13]([OH:14])[OH:17])[CH2:8][N:7]([CH2:35][C:31]2[N:30]([CH3:29])[CH:34]=[CH:33][N:32]=2)[CH2:6]1

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 10340Sodium CarbonateHCID 24436Sodium SulfateHCID 1395751-Methyl-2-imidazolecarboxaldehydeHCID 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

Product 1

HCID 57331478(3R,4S)-3-amino-4-(3-boronopropyl)-1-((1-methyl-1H-imidazol-2-yl)methyl)pyrrolidine-3-carboxylic acidYield 90.3%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

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) and 1-methylimidazole-2-carboxaldehyde (83 mg, 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 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-((1-methyl-1H-imidazol-2-yl)methyl)pyrrolidine-3-carboxylic acid (140 mg, 67%) as a pale yellow solid. NMR (D2O) δ 7.37 (s, 2 H), 4.35-4.50 (m, 2 H), 3.80 (s, 3 H), 3.40-3.60 (m, 3 H), 2.75-2.85 (m, 1 H), 2.43 (m, 1 H), 1.48 (s, 1 H), 1.15-1.30 (3 H), 0.60-0.70 (m, 2 H). MS (m+1): 311.0; MS (m−H2O+1): 293.1.

Workup

  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

Sources & evidence

ORD record
ord-794447f200b74ca9b735308a43ce96c1
Source dataset
uspto-grants-2016_09
Patent number
US09440995B2

Linked notes

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