Potassium Carbonate → 1,1-Dimethylethyl 4-{[(benzothien-7-yl)methyl]-(2-methylpropyl)amino}-piperidine-1-carboxylate

HRID 2111887Notes

Reaction equation

HRID 2111887 reaction equation
Br[CH2:2][C:3]1[C:8]2[S:9][CH:10]=[CH:11][C:7]=2[CH:6]=[CH:5][CH:4]=1.[CH3:12][CH:13]([CH3:29])[CH2:14][NH:15][CH:16]1[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[S:9]1[C:8]2[C:3]([CH2:2][N:15]([CH2:14][CH:13]([CH3:29])[CH3:12])[CH:16]3[CH2:17][CH2:18][N:19]([C:22]([O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:23])[CH2:20][CH2:21]3)=[CH:4][CH:5]=[CH:6][C:7]=2[CH:11]=[CH:10]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 107517617-(Bromomethyl)-1-benzothiopheneHCID 15380699tert-Butyl 4-(isobutylamino)piperidine-1-carboxylate

Product 1

HCID 685752951,1-Dimethylethyl 4-{[(benzothien-7-yl)methyl]-(2-methylpropyl)amino}-piperidine-1-carboxylateYield 57.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 7-bromomethyl-benzo[b]thiophene (0.63 g, 2.8 mmol, 1 eq) and 1,1-dimethylethyl 4-[(2-methylpropyl)amino]piperidine-1-carboxylate (0.71 g, 2.8 mmol, 1 eq) in acetonitrile (25 ml) is added potassium carbonate (0.62 g, 4.4 mmol, 1.6 eq). The mixture is heated to reflux for 16 hours. The solution is filtered and the solvent removed in vacuo. The resulting oil is purified on a 40 g Redisep column using a gradient of 0-20% ethyl acetate/iso-hexane to give 1,1-dimethylethyl 4-{[(benzothien-7-yl)methyl]-(2-methylpropyl)amino}-piperidine-1-carboxylate as an oil (0.65 g, 40%); mass spectrum (LCMS): m/z=403.3 (M++1), Rt=4.40 (6 minute gradient); 1H NMR (300 MHz, CDCl3): δ=7.79-7.65 (1 H, m), 7.46-7.40 (1 H, m), 7.37-7.30 (3 H, m), 4.18-4.06 (4H, m), 3.90 (2 H, s), 2.67-2.44 (3 H, m), 2.32-2.22 (2 H, m), 1.87-1.37 (8 H, m), 144 (4H, s) and 0.92-0.83 (6 H, m).

Workup

  1. temperatureThe mixture is heated
  2. temperatureto reflux for 16 hours
  3. filtrationThe solution is filtered
  4. customthe solvent removed in vacuo
  5. customThe resulting oil is purified on a 40 g Redisep column

Sources & evidence

ORD record
ord-2ffad3118846454081341dadc667a0e8
Source dataset
uspto-grants-2009_04
Patent number
US07521462B2

Reaction notes

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