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 383500Notes

Reaction equation

HRID 383500 reaction equation
[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

Participants

8

Reactant 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

Product 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

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

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%.

Workup

  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

Sources & evidence

ORD record
ord-766c7ce011e14b13a85d868be924f60a
Source dataset
uspto-grants-2013_02
Patent number
US08367664B2

Reaction notes

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