Chlorotrimethylsilane → 3-Oxo-3-[(pyridin-3-yl)amino]propanoic acid

HRID 2193673Notes

Reaction equation

HRID 2193673 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([NH2:7])[CH:2]=1.C[Si](Cl)(C)C.CC1(C)[O:19][C:18](=O)[CH2:17][C:16](=[O:21])[O:15]1>C(Cl)Cl>[O:19]=[C:18]([NH:7][C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1)[CH2:17][C:16]([OH:21])=[O:15]

Participants

5

Reactant 3

HCID 6397ChlorotrimethylsilaneHCID 100093-AminopyridineHCID 162492,2-Dimethyl-1,3-dioxane-4,6-dione

Product 1

HCID 219394713-Oxo-3-[(pyridin-3-yl)amino]propanoic acidYield 26.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of pyridine-3-amine (1 g, 10.6 mmol) in DCM (100 mL) was added TMSCl (1.3 mL, 10.6 mmol) at room temperature. The reaction mixture was stirred for 30 min. 2,2-Dimethyl-1,3-dioxane-4,6-dione (1.44 g, 10.6 mmol) was added and the combined mixture stirred overnight and concentrated under reduced pressure. The residue was dissolved in dilute NaHCO3 solution and washed with EtOAc. The aqueous phase was collected and acidified with cone. HCl to pH˜3 and extracted with EtOAc. The extract was dried over anhydrous Na2SO4, filtered and concentrated. The remaining solid was purified by flash chromatography (eluent CHCl3/MeOH/AcOH 8:1:0.1) to afford the title compound 39 as a white solid (0.5 g, 26% yield). 1H NMR (DMSO-d6) δ (ppm): 12.04 (bs, 1H), 9.67 (s, 1H), 8.18 (d, 1H), 8.01 (d, 1H), 7.29 (m, 1H), 2.97 (s, 2H). MS (m/z): 181.1 (M+H).

Workup

  1. stirringthe combined mixture stirred overnight
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe residue was dissolved in dilute NaHCO3 solution
  4. washwashed with EtOAc
  5. customThe aqueous phase was collected
  6. extractionHCl to pH˜3 and extracted with EtOAc
  7. dry with materialThe extract was dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe remaining solid was purified by flash chromatography (eluent CHCl3/MeOH/AcOH 8:1:0.1)

Sources & evidence

ORD record
ord-7add83cd16174b5eaa1d614bab68cf8b
Source dataset
uspto-grants-2012_12
Patent number
US08329726B2

Reaction notes

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