2-(Di-tert-butylphosphino)biphenyl → (S)-2-sec-butylamino-6-methanesulfonylamino-isonicotinic acid methyl ester

HRID 732365ノート

反応式

HRID 732365 の反応式
[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8](Cl)[N:7]=[C:6]([NH:11][C@H:12]([CH2:14][CH3:15])[CH3:13])[CH:5]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[CH3:38][S:39]([NH2:42])(=[O:41])=[O:40].[Na]>C1(C)C=CC=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]>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8]([NH:42][S:39]([CH3:38])(=[O:41])=[O:40])[N:7]=[C:6]([NH:11][C@H:12]([CH2:14][CH3:15])[CH3:13])[CH:5]=1

参加物

6

反応物 3

HCID 27342152-(Di-tert-butylphosphino)biphenylHCID 86614996HCID 86614996、化合物HCID 86614997HCID 86614997、化合物

生成物 1

HCID 68814626(S)-2-sec-butylamino-6-methanesulfonylamino-isonicotinic acid methyl ester収率 46.4%

試薬・触媒・溶媒 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium触媒HCID 1140Toluene溶媒

反応条件

温度
99 °C

実験手順

Add to a 300 mL of autoclave reactor (s)-(+)-2-sec-butylamino-6-chloro-isonicotinic acid methyl ester (12.46 g, 0.05134 mol), bis(dibenzylideneacetone)-palladium (0) (2.35 g, 0.002567 mol), 2-di-tert-butylphosphino biphenyl (1.53 g, 0.005134 mol) and sodium methanesulfonamide (12.02 g, 0.1027 mol) in toluene (250 mL). Flush with nitrogen 3 times and heat to 99° C. for 24 h. Filter and dissolve the filter cake in water (400 mL). Extract the aqueous layer with chloroform (3×200 mL), dry (magnesium sulfate) and concentrate. Dissolve the crude product in dichloromethane (20 mL) and precipitate out by adding hexanes (400 mL) to give a solid (7.18 g, 46%). m.p. 118.6-123.0° C., 1H NMR (500 MHz, DMSO) δ 6.87 (s, 1H), 6.69 (s, 1H), 4.83 (br, 1H), 3.94 (s, 3H), 3.74 (m, 1H), 3.27 (s, 1H), 1.60 (m, 2H) 1.25 (d, J=7 Hz, 3H), 0.99 (t, J=7 Hz, 3H).

後処理

  1. customFlush with nitrogen 3 times
  2. filtrationFilter
  3. dissolutiondissolve the filter cake in water (400 mL)
  4. extractionExtract the aqueous layer with chloroform (3×200 mL)
  5. dry with materialdry (magnesium sulfate)
  6. concentrationconcentrate
  7. dissolutionDissolve the crude product in dichloromethane (20 mL)
  8. customprecipitate out
  9. additionby adding hexanes (400 mL)

出典と根拠

ORDレコード
ord-667f43aa396140229fc88d6a0f4ecf80
出典データセット
uspto-grants-2009_09
特許番号
US07585885B2

反応ノート

読み込み中…