Cesium carbonate → N-(6-Methoxypyridin-2-yl)pivalamide

HRID 1943147Notes

Reaction equation

HRID 1943147 reaction equation
[CH3:1][C:2]([CH3:7])([CH3:6])[C:3]([NH2:5])=[O:4].C([O-])([O-])=O.[Cs+].[Cs+].Cl[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[N:16]=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CO.C(Cl)Cl>[CH3:1][C:2]([CH3:7])([CH3:6])[C:3]([NH:5][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[N:16]=1)=[O:4]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 12957TrimethylacetamideHCID 870092-Chloro-6-methoxypyridine

Product 1

HCID 17750200N-(6-Methoxypyridin-2-yl)pivalamideYield 75%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 21226129Dichloromethane methanolSolvent

Procedure

A suspension of trimethylacetamide (18.08 g, 178.744 mmol), Cs2CO3 (68.823 g, 211.242 mmol), Pd2(dba)3 (1.488 g, 1.625 mmol) and Xantphos (4,5-bis-(diphenylphosphino)-9,9-dimethylxanthene) (1.880 g, 3.249 mmol) in dry, degassed 1,4-dioxane (800 ml) under argon was sonicated for 0.25 h and then treated with 2-chloro-6-(methyloxy)pyridine (19.32 ml, 162.494 mmol). The mixture was then heated at reflux for 24 h. The mixture was evaporated, treated with water (1 L) and extracted 3×DCM (1 L and then 2×500 ml). The organic extracts were dried (MgSO4), evaporated and chromatographed (50-100% DCM/40-60 Petroleum ether then 0-5% methanol/DCM) to give title compound as a yellow solid (25.191 g, 121.111 mmol, 75%). Impure fractions were recolumed (eluting as above) to give more product (4.990 g, 23.990 mmol, 15%). Total yield of 90%.

Workup

  1. customin dry
  2. customdegassed 1,4-dioxane (800 ml) under argon
  3. customwas sonicated for 0.25 h
  4. temperatureThe mixture was then heated
  5. temperatureat reflux for 24 h
  6. customThe mixture was evaporated
  7. additiontreated with water (1 L)
  8. extractionextracted 3×DCM (1 L
  9. dry with materialThe organic extracts were dried (MgSO4)
  10. customevaporated
  11. customchromatographed (50-100% DCM/40-60 Petroleum ether

Sources & evidence

ORD record
ord-22dc20153bd54010842c5f7f3f86e5c6
Source dataset
uspto-grants-2013_03
Patent number
US08389524B2

Reaction notes

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