Sulfuric acid magnesium salt (1:1) → tert-butyl(2S,3S)-3-methyl-2-{3-[(2-methyl-3-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}pentanoate

HRID 1174151Notes

Reaction equation

HRID 1174151 reaction equation
[NH2:1][CH2:2][CH2:3][NH:4][C@@H:5]([C@@H:13]([CH3:16])[CH2:14][CH3:15])[C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].[CH3:17][C:18]1[N:25]=[CH:24][CH:23]=[CH:22][C:19]=1[CH:20]=O.[O-]S([O-])(=O)=O.[Mg+2].[BH4-].[Na+].[C:34](=O)(OC1C=CC([N+]([O-])=O)=CC=1)[O:35]C1C=CC([N+]([O-])=O)=CC=1>ClCCl.CO.ClCCCl>[CH3:16][C@@H:13]([CH2:14][CH3:15])[C@H:5]([N:4]1[CH2:3][CH2:2][N:1]([CH2:20][C:19]2[C:18]([CH3:17])=[N:25][CH:24]=[CH:23][CH:22]=2)[C:34]1=[O:35])[C:6]([O:8][C:9]([CH3:10])([CH3:11])[CH3:12])=[O:7]

Participants

9

Reactant 5

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 78756Bis(4-nitrophenyl) carbonateHCID 4311764Sodium borohydrideHCID 110838812-Methylpyridine-3-carbaldehydeHCID 86598803tert-butyl(2S,3S)-2-[(2-aminoethyl)amino]-3-methylpentanoate

Product 1

HCID 67406934tert-butyl(2S,3S)-3-methyl-2-{3-[(2-methyl-3-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}pentanoateYield 61.3%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A solution containing the product from Example 3G (2.4 g, 10.43 mmol) in dichloromethane (24 mL) was treated with the product from Example 15A (1.3 g, 10.74 mmol) and MgSO4 (4.6 g, 38.21 mmol), stirred at 25° C. for 2.5 hours, filtered and concentrated. A solution of the residue in methanol (24 mL) at 0° C. was treated with sodium borohydride (0.5 g, 13.2 mmol), and stirred at 25° C. for 3 hours. The solvent was concentrated and the reaction was partitioned between ethyl acetate and saturated NaHCO3, and the organic phase was washed with brine and dried over MgSO4, filtered and concentrated. A solution of the residue (3.4 g) in 1,2 dichloroethane (30 mL was treated with bis(4-nitrophenyl) carbonate (3.8 g, 12.5 mmol), heated at 60° C. for 16 hours, and partitioned between ethyl acetate and saturated NaHCO3. The organic phase was washed with brine, dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel eluting with ethyl acetate to give the title compound (2.31 g, 60% yield).

Workup

  1. filtrationfiltered
  2. concentrationconcentrated
  3. stirringstirred at 25° C. for 3 hours
  4. concentrationThe solvent was concentrated
  5. customthe reaction was partitioned between ethyl acetate and saturated NaHCO3
  6. washthe organic phase was washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. temperatureheated at 60° C. for 16 hours
  11. custompartitioned between ethyl acetate and saturated NaHCO3
  12. washThe organic phase was washed with brine
  13. dry with materialdried over MgSO4
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customThe residue was chromatographed on silica gel eluting with ethyl acetate

Sources & evidence

ORD record
ord-6a7523324d8a4d6bb9a207442cb79a6a
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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