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 333381Notes

Reaction equation

HRID 333381 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-e578c49b1c4a450c8d1d19745cdd7384
Source dataset
uspto-grants-2014_11
Patent number
US08877923B2

Reaction notes

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