1,4-Dioxa-8-azaspiro(4.5)decane → 1-(5-Cyano-2-methoxyphenyl)-4-piperidone ethylene ketal

HRID 1976152ノート

反応式

HRID 1976152 の反応式
[O:1]1[C:5]2([CH2:10][CH2:9][NH:8][CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Br[C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][C:29]=1[O:30][CH3:31])[C:25]#[N:26]>C1(C)C=CC=CC=1>[CH2:3]1[O:4][C:5]2([CH2:10][CH2:9][N:8]([C:22]3[CH:23]=[C:24]([C:25]#[N:26])[CH:27]=[CH:28][C:29]=3[O:30][CH3:31])[CH2:7][CH2:6]2)[O:1][CH2:2]1

参加物

5

反応物 3

HCID 674351,4-Dioxa-8-azaspiro(4.5)decaneHCID 7360493-Bromo-4-methoxybenzonitrileHCID 2724254Sodium bis(trimethylsilyl)amide

生成物 1

HCID 572003271-(5-Cyano-2-methoxyphenyl)-4-piperidone ethylene ketal収率 38.2%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

1,4-Dioxa-8-azaspiro[4.5]decane (1.47 g, 10.28 mmol), sodium bis(trimethylsilyl)amide (1 N in THF, 12 ml), and PdCl2(p(o-tolyl)3)2 [2 mol % catalyst prepared from bis(acetonitrile) Pd(II) chloride(53 mg, 0.206 mmol) and tri(o-tolyl)phosphine (125 mg, 0.52 mmol)] were added to a solution of 3-bromo-4-methoxybenzonitrile (1.82 g, 8.58 mmol) in toluene (40 ml). The reaction was stirred for 5 hours at 100° C. The reaction was concentrated in vacuo, diluted with water, and extracted with methylene chloride. The organic extract was concentrated in vacuo, and the residue purified by chromatography on silica gel using hexane/ethyl acetate (80/20) as the eluent to give 1-(5-cyano-2-methoxyphenyl)-4-piperidone ethylene ketal (900 mg, 38%). This ketal was dissolved in dioxane (15 ml) and HCl (6 N, 2.2 ml) and stirred at 100° C. for 2 h. The solution was cooled, quenched with saturated aqueous NaHCO3. The mixture was extracted with methylene chloride, concentrated in vacuo, and purified by chromatography on silica gel using hexane/ethyl acetate (80/20) as the eluent to give 1-(5-cyano-2-methoxyphenyl)-4-piperidone (125 mg, 19%).

後処理

  1. concentrationThe reaction was concentrated in vacuo
  2. additiondiluted with water
  3. extractionextracted with methylene chloride
  4. extractionThe organic extract
  5. concentrationwas concentrated in vacuo
  6. customthe residue purified by chromatography on silica gel

出典と根拠

ORDレコード
ord-38f4bfe42b794dafb365af318b2d0579
出典データセット
uspto-grants-2001_05
特許番号
US06225324B1

反応ノート

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