Acetic Acid → (S)-(1-(4-fluorobenzyl)-1H-indol-2-yl)(4-(((1-phenylethyl)amino)methyl)piperidin-1-yl)methanone

HRID 83665Notes

Reaction equation

HRID 83665 reaction equation
[F:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:9]=[C:8]2[C:16]([N:18]2[CH2:23][CH2:22][CH:21]([CH:24]=O)[CH2:20][CH2:19]2)=[O:17])=[CH:4][CH:3]=1.[CH3:28][C@H:29]([NH2:36])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C([BH3-])#N.[Na+].C(O)(=O)C>C1COCC1>[F:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:9]=[C:8]2[C:16]([N:18]2[CH2:23][CH2:22][CH:21]([CH2:24][NH:36][C@H:29]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH3:28])[CH2:20][CH2:19]2)=[O:17])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 758181-Phenethylamine, (-)-HCID 5003444Sodium cyanoborohydrideHCID 866718991-(1-(4-fluorobenzyl)-1H-indole-2-carbonyl)piperidine-4-carbaldehyde

Product 1

HCID 66571571(S)-(1-(4-fluorobenzyl)-1H-indol-2-yl)(4-(((1-phenylethyl)amino)methyl)piperidin-1-yl)methanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1-(1-(4-fluorobenzyl)-1H-indole-2-carbonyl)piperidine-4-carbaldehyde (35 mg, 0.096 mmol) was dissolved in THF (2 mL) and (S)-α-methylbenzylamine (0.013 mL, 0.115 mmol) was added. The solution was stirred at rt for 10 h, at which time the THF was removed in vacuo and the residue dissolved in EtOH (5 mL), and sodium cyanoborohydride (13 mg, 0.192 mmol) and a catalytic drop of glacial acetic acid were added. Stirring was permitted for 14 h, at which time the solvent was removed in vacuo, the residue was taken up in EtOAc. The organic phase was washed with 10% aq. sodium carbonate, dried over magnesium sulfate, and concentrated. Purification was accomplished via silica gel flash chromatography (30 g silica gel, 5:95 7M methanolic ammonia:ethyl acetate.) The title compound was obtained as a yellow oil. (Yield: 21 mg, 0.045 mmol, 47%) 1H NMR (400 MHz, CDCl3) 7.62, 7.39-7.23, 7.14, 7.09-7.02, 6.86, 6.57, 5.45, 4.59, 4.06, 3.76-3.63, 2.74, 2.39-2.15, 1.76-1.52, 1.33, 0.98, 0.63

Workup

  1. customwas removed in vacuo
  2. dissolutionthe residue dissolved in EtOH (5 mL)
  3. customthe solvent was removed in vacuo
  4. washThe organic phase was washed with 10% aq. sodium carbonate
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customPurification
  8. customwas obtained as a yellow oil

Sources & evidence

ORD record
ord-e258ba044a5c45cb94f688d6f9b18740
Source dataset
uspto-grants-2014_09
Patent number
US08846684B2

Reaction notes

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