Triethylamine → N-(6-chloro-4-methylpyridin-2-yl)pivalamide

HRID 2188905Notes

Reaction equation

HRID 2188905 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][N+:5]([O-])=[C:4]([NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12])[CH:3]=1.CCN(CC)CC.O=P(Cl)(Cl)[Cl:25]>>[Cl:25][C:6]1[N:5]=[C:4]([NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12])[CH:3]=[C:2]([CH3:1])[CH:7]=1

Participants

4

Reactant 3

HCID 8471TriethylamineHCID 24813Phosphorus oxychlorideHCID 178428734HCID 178428734, compound

Product 1

HCID 59165851N-(6-chloro-4-methylpyridin-2-yl)pivalamideYield 16%

Conditions

Temperature
100 °C

Procedure

To a solution of 4-methyl-2-pivalamidopyridine 1-oxide (3.0 g, 14 mmol) in POCl3 (30 mL) was added Et3N (6.0 mL, 43 mmol) drop-wise at 0° C. Then mixture was stirred at 100° C. for 3 days. The mixture was quenched with water, treated with aqueous NaOH to pH 8-9, and extracted with ethyl acetate (50 mL×3). The combined organic extracts were dried over anhydrous Na2SO4, evaporated under vacuum and purified by chromatography on silica gel (15% ethyl acetate in petroleum ether) to afford N-(6-chloro-4-methylpyridin-2-yl)pivalamide (520 mg, 16%). 1H NMR (CDCl3, 300 MHz) δ 8.03 (s, 1H), 7.93 (br s, 1H), 6.87 (s, 1H), 2.33 (s, 3H), 1.29 (s, 9H).

Workup

  1. customThe mixture was quenched with water
  2. additiontreated with aqueous NaOH to pH 8-9
  3. extractionextracted with ethyl acetate (50 mL×3)
  4. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  5. customevaporated under vacuum
  6. custompurified by chromatography on silica gel (15% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-3316a3b4466f42a386a740d3a51cedf0
Source dataset
uspto-grants-2012_12
Patent number
US08324207B2

Reaction notes

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