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

HRID 883763

반응식

HRID 883763 반응식
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]

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매

반응 조건

온도
105 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-4e5ca6ee04e14a3b96269a27e5975d9d
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08236953B2

연결된 노트

불러오는 중…