Pivaloyl chloride → N-(4-Chloropyridin-2-yl)pivalamide

HRID 416691Notes

Reaction equation

HRID 416691 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][N:3]=1.[CH3:9][C:10]([CH3:15])([CH3:14])[C:11](Cl)=[O:12]>N1C=CC=CC=1>[Cl:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:11](=[O:12])[C:10]([CH3:15])([CH3:14])[CH3:9])[CH:7]=1

Participants

4

Reactant 2

HCID 62493Pivaloyl chlorideHCID 5818662-Amino-4-chloropyridine

Product 1

HCID 10656204N-(4-Chloropyridin-2-yl)pivalamideYield 74%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

This compound was prepared as reported by K. S. Gudmundsson et al, Synthetic Communications 1997, 27 (5), 861-870: To a stirred solution of 2-amino-4-chloropyridine (0.723 g, 5.62 mmol) in anhydrous pyridine (2.8 ml) was dropwise added trimethylacetyl chloride (1.02 g, 8.46 mmol). The reaction mixture was stirred at room temperature for 4.5 h under argon, then partitioned between ethyl acetate (70 ml) and water (50 ml). The aqueous layer was extracted with ethyl acetate (2×30 ml), and the combined organics were washed with saturated aqueous NaHCO3 (40 ml), brine (50 ml), dried (Na2SO4), and concentrated in vacuo. The residue was absorbed on silica gel and the free running powder was placed on a 50 g isolute silica column. Elution with 20% ethyl acetate in hexanes and 25% ethyl acetate in hexanes afforded the title compound as a white solid (0.880 g, 74%); 1H-NMR (250 Mz, DMSO-d6) 1.24 (s, 9H, C(CH3)3), 7.25 (dd, J=1.91 Hz, 5.36 Hz, 1H, 5-H), 8.17 (d, J=1.87 Hz, 1H, 3-H), 8.34 (d, J=5.35 Hz, 1H, 6-H), 10.09 (s, 1H, CONH); LC-MS (ESI, m/z) 6.91 min—213, 215 [(M+H)+, Cl isotopic pattern].

Workup

  1. customThis compound was prepared
  2. custompartitioned between ethyl acetate (70 ml) and water (50 ml)
  3. extractionThe aqueous layer was extracted with ethyl acetate (2×30 ml)
  4. washthe combined organics were washed with saturated aqueous NaHCO3 (40 ml), brine (50 ml)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was absorbed on silica gel
  8. washElution with 20% ethyl acetate in hexanes and 25% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-d498b3d1afab4c919d7e197d59a4d19d
Source dataset
uspto-grants-2012_01
Patent number
US08088761B2

Reaction notes

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