Acetic Acid → (3R,4S)-3-amino-4-(3-boronopropyl)-1-(pyridin-2-ylmethyl)pyrrolidine-3-carboxylic acid

HRID 61375Notes

Reaction equation

HRID 61375 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.[N:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=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:30]2[CH:31]=[CH:32][CH:33]=[CH:34][N:29]=2)[CH2:6]1

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 10340Sodium CarbonateHCID 142732-PyridinecarboxaldehydeHCID 24436Sodium SulfateHCID 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 57331477(3R,4S)-3-amino-4-(3-boronopropyl)-1-(pyridin-2-ylmethyl)pyrrolidine-3-carboxylic acidYield 91.8%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
40 °C

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 pyridine-2-carboxaldehyde (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-(pyridin-2-ylmethyl)pyrrolidine-3-carboxylic acid (141 mg, 74%) as a white solid. NMR (D2O) δ 8.63 (m, 1 H), 8.20 (m, 1 H), 7.65-7.85 (m, 2 H), 4.50-4.65 (m, 2 H), 3.86 (d, J=12.5 Hz, 1 H), 3.70 (m, 2H), 3.22 (t, J=11 Hz, 1H), 2.55 (m, 1 H), 1.55 (m, 1 H), 1.15-1.35 (m, 3 H), 0.60-0.70 (m, 2 H). MS (m+1): 308.0; MS (m−H2O+1): 290.2.

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-8219856641f949f38e25b15a732b0ac0
Source dataset
uspto-grants-2016_09
Patent number
US09440995B2

Reaction notes

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