Cesium carbonate → 1,1-Dimethylethyl 4-[(3-cyanophenyl)amino]-1-piperidinecarboxylate

HRID 883763

反応式

HRID 883763 の反応式
C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:53][CH:54]1[CH2:59][CH2:58][N:57]([C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[CH2:56][CH2:55]1.Br[C:68]1[CH:69]=[C:70]([CH:73]=[CH:74][CH:75]=1)[C:71]#[N:72]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:71]([C:70]1[CH:69]=[C:68]([NH:53][CH:54]2[CH2:55][CH2:56][N:57]([C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[CH2:58][CH2:59]2)[CH:75]=[CH:74][CH:73]=1)#[N:72]

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 233813-BromobenzonitrileHCID 634876Binap, (A+-)-HCID 12682914-Amino-1-Boc-piperidine

生成物 1

HCID 252237961,1-Dimethylethyl 4-[(3-cyanophenyl)amino]-1-piperidinecarboxylate収率 82.4%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
105 °C

実験手順

A mixture of BINAP (560 mg, 0.9 mmol), palladium acetate (135 mg, 0.6 mmol) and cesium carbonate (2.932 g, 9 mmol) in 1,4-dioxane (10 ml) was sonicated for 50 minutes. 1,1-Dimethylethyl 4-amino-1-piperidinecarboxylate (1.2 g, 6 mmol) and 3-bromobenzonitrile (1.638 g, 9 mmol) were added and the mixture heated to 105° C. overnight under an argon atmosphere. On cooling, the solvent was removed in vacuo and the residue partitioned between water (100 ml) and EtOAc (100 ml). The organic layer was separated, dried and concentrated and the crude product purified by column chromatography. Elution with a 0-50% Et2O/petroleum ether gradient gave the title compound as a white solid (1.49 g). δH (CDCl3, 250 MHz) 7.22 (1H, t), 6.95 (1H, dd), 6.77 (2H, m), 4.07 (2H, m), 3.77 (1H, m), 3.41 (1H, m), 2.93 (2H, m), 2.03 (2H, m), 1.47 (9H, s), 1.34 (2H, m). MS (ES): MH+ 302.

後処理

  1. customwas sonicated for 50 minutes
  2. temperatureOn cooling
  3. customthe solvent was removed in vacuo
  4. customthe residue partitioned between water (100 ml) and EtOAc (100 ml)
  5. customThe organic layer was separated
  6. customdried
  7. concentrationconcentrated
  8. customthe crude product purified by column chromatography
  9. washElution with a 0-50% Et2O/petroleum ether gradient

出典と根拠

ORDレコード
ord-4e5ca6ee04e14a3b96269a27e5975d9d
出典データセット
uspto-grants-2012_08
特許番号
US08236953B2

関連ノート

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