Cesium carbonate → Tert-butyl 4-formyl-6-methylpyridin-2-ylcarbamate

HRID 1814016ノート

反応式

HRID 1814016 の反応式
Cl[C:2]1[CH:7]=[C:6]([CH:8]=[O:9])[CH:5]=[C:4]([CH3:10])[N:3]=1.C([NH:15][C:16](=[O:18])[O-:17])(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:25][C:26]1(C)[C:52]2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=C[C:27]1=2>O1CCOCC1.O.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]>[CH:8]([C:6]1[CH:5]=[C:4]([CH3:10])[N:3]=[C:2]([NH:15][C:16](=[O:18])[O:17][C:26]([CH3:52])([CH3:27])[CH3:25])[CH:7]=1)=[O:9]

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27629752-Chloro-6-methylpyridine-4-carbaldehydeHCID 21252905Tert-butylcarbamate

生成物 1

HCID 22504283Tert-butyl 4-formyl-6-methylpyridin-2-ylcarbamate

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

2-Chloro-6-methyl-pyridine-4-carbaldehyde (13-2, 0.609 g, 3.91 mmol), tert-butylcarbamate (0.550 g, 4.70 mmol), cesium carbonate (1.91 g, 5.87 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.036 g, 0.040 mmol) and Xantphos (0.068 g, 0.030 mmol) were stirred in 10 mL of anhydrous dioxane under N2. The reaction was heated to 80° C. and after 18 hours the reaction was cooled to room temperature. The mixture was diluted with water and extracted 3× with EtOAc. The extracts were dried over Na2SO4, filtered and concentrated. Purification by flash column chromatography afforded impure tert-butyl 4-formyl-6-methylpyridin-2-ylcarbamate. This aldehyde was dissolved in 2 mL of 1,2-dichloroethane. N-Acetylpiperazine (0.074 g, 0.58 mmol) was added followed by addition of 0.05 mL HOAc and NaBH(OAc)3 (0.122 g, 0.58 mmol). After 3 hours the reaction was quenched by the addition of half-saturated NaHCO3 (aq). The mixture was extracted 3× with DCM (dichloromethane) and the extracts were dried over Na2SO4, filtered and concentrated to afford the titled compound, 13-3. 1H NMR (CDCl3) δ 7.67 (s, 1H), 7.47 (s, 1H), 6.84 (s, 1H), 3.64 (t, 2H, J=4.9 Hz), 3.47 (m, 4H), 2.44 (m, 7H), 2.09 (s, 3H), 1.51 (s, 9H).

後処理

  1. temperaturewas cooled to room temperature
  2. extractionextracted 3× with EtOAc
  3. dry with materialThe extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by flash column chromatography

出典と根拠

ORDレコード
ord-1826ff4524a340659fde683f16c80777
出典データセット
uspto-grants-2005_04
特許番号
US06875767B2

反応ノート

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