Acetic Acid → methyl 1-{4-[(5E)-5-(5,6-difluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-2,2-dimethyl-2,5-dihydrofuran-3-yl]benzyl}piperidine-4-carboxylate

HRID 2196151노트

반응식

HRID 2196151 반응식
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[NH:7][C:6](=[O:12])/[C:5]/2=[C:13]1\[CH:14]=[C:15]([C:20]2[CH:27]=[CH:26][C:23]([CH:24]=O)=[CH:22][CH:21]=2)[C:16]([CH3:19])([CH3:18])[O:17]\1.[NH:28]1[CH2:37][CH2:36][CH:31]([C:32]([O:34][CH3:35])=[O:33])[CH2:30][CH2:29]1.C(O)(=O)C.C([BH3-])#N.[Na+].C1COCC1>CN(C=O)C.CO.O>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[NH:7][C:6](=[O:12])/[C:5]/2=[C:13]1\[CH:14]=[C:15]([C:20]2[CH:27]=[CH:26][C:23]([CH2:24][N:28]3[CH2:37][CH2:36][CH:31]([C:32]([O:34][CH3:35])=[O:33])[CH2:30][CH2:29]3)=[CH:22][CH:21]=2)[C:16]([CH3:18])([CH3:19])[O:17]\1

참가 물질

8

반응물 4

HCID 176Acetic AcidHCID 424914Methyl isonipecotateHCID 589263884-[(5E)-5-(5,6-difluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-2,2-dimethyl-2,5-dihydrofuran-3-yl]benzaldehydeHCID 131730117sodium cyanoborohydride THF

생성물 1

HCID 58926253methyl 1-{4-[(5E)-5-(5,6-difluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-2,2-dimethyl-2,5-dihydrofuran-3-yl]benzyl}piperidine-4-carboxylate

시약·촉매·용매 3

HCID 887Methanol용매HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

A mixture of 4-[(5E)-5-(5,6-difluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-2,2-dimethyl-2,5-dihydrofuran-3-yl]benzaldehyde (60 mg, 0.16 mmol), methyl isonipecotate (50 mg, 0.35 mmol), and 100 mg of 4 Å molecular sieves in 5 mL of anhydrous DMF was stirred under nitrogen for 16 hours. Acetic acid (20 mg) and 1M sodium cyanoborohydride/THF solution (0.35 mL, 0.35 mmol) were then added. The mixture was diluted with 5 mL of anhydrous methanol, stirred at room temperature for 1 hour, and poured into 100 mL of water with stirring. The resulting precipitates were filtered, washed with water, and dried in vacuo to give the crude product, which was purified through silica gel column with 1-5% MeOH/CHCl3 to give methyl 1-{4-[(5E)-5-(5,6-difluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-2,2-dimethyl-2,5-dihydrofuran-3-yl]benzyl}piperidine-4-carboxylate as yellow solid. Yield: 50 mg, 62%.

후처리

  1. stirringstirred at room temperature for 1 hour
  2. stirringwith stirring
  3. customThe resulting precipitates
  4. filtrationwere filtered
  5. washwashed with water
  6. customdried in vacuo
  7. customto give the crude product, which
  8. customwas purified through silica gel column with 1-5% MeOH/CHCl3

출처 및 근거

ORD 기록
ord-c041b6894ee343e78cf65886347195ad
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08338415B2

반응 노트

불러오는 중…