Sodium Carbonate → HCID 178508117, compound

HRID 61366Notes

Reaction equation

HRID 61366 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.S([O-])([O-])(=O)=O.[Na+].[Na+].[NH:36]1[CH:40]=[C:39]([CH:41]=O)[N:38]=[CH:37]1.C(O[BH-](OC(=O)C)OC(=O)C)(=[O:45])C.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>ClCCCl.C(O)(=O)C>[NH:36]1[CH:40]=[C:39]([CH2:41][N:7]2[CH2:8][C@H:9]([CH2:10][CH2:11][CH2:12][B:13]([OH:14])[OH:17])[C@:5]([NH2:4])([C:22]([OH:23])=[O:45])[CH2:6]2)[N:38]=[CH:37]1

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 24436Sodium SulfateHCID 764281H-Imidazole-4-carbaldehydeHCID 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 178508117HCID 178508117, compoundYield 25.7%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 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) in anhydrous 1,2-dichloroethane (5 mL) was treated with anhydrous sodium sulfate (1 g) and imidazole-4-carboxaldehyde (110 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 saturate 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)-1-((1H-imidazol-4-yl)methyl)-3-amino-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid (38 mg, 21%) as a pale yellow granular solid. NMR (D2O) 8.74 (s, 1 H), 7.71 (s, 1 H), 4.60-4.80 (m, 2 H), 3.96 (d, J=12.5 Hz, 1H), 3.80 (dd, J1=11 Hz, J2=8 Hz, 1 H), 3.71 (d, J=12.5 Hz, 1 H), 3.40 (t, J=11.5 Hz, 1 H), 2.50-2.65 (m, 1 H), 1.50-1.65 (m, 1 H), 1.15-1.35 (m, 3 H), 0.60-0.70 (m, 2 H). MS (m−H2O+1): 279.0; MS (m−2 H2O+1): 261.3.

Workup

  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
  5. concentrationsaturate aqueous sodium chloride (20 mL each)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customisolated

Sources & evidence

ORD record
ord-a156c32cd2444e0d9a9dc2ff376755ce
Source dataset
uspto-grants-2016_09
Patent number
US09440995B2

Reaction notes

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