Sodium hydride → 4-[3-(4-Methyl-indol-1-yl)-propyl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 660025Notes

Reaction equation

HRID 660025 reaction equation
[CH3:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.[H-].[Na+].[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([CH2:26][CH2:27][CH2:28]OS(C)(=O)=O)[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14]>CN(C=O)C.C(Cl)(Cl)Cl>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([CH2:26][CH2:27][CH2:28][N:6]2[C:7]3[C:3](=[C:2]([CH3:1])[CH:10]=[CH:9][CH:8]=3)[CH:4]=[CH:5]2)[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 852824-MethylindoleHCID 21190098Tert-butyl 4-(3-((methylsulfonyl)oxy)propyl)piperidine-1-carboxylate

Product 1

HCID 688726324-[3-(4-Methyl-indol-1-yl)-propyl]-piperidine-1-carboxylic acid tert-butyl esterYield 55.2%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of 4-methyl-1H-indole (1.0 g, 7.62 mmol) in DMF (20 mL), cooled at 0° C., was added NaH (60% in mineral oil; 0.40 mg, 9.91 mmol). After 45 min at 0° C., a solution of 4-(3-methanesulfonyloxy-propyl)-piperidine-1-carboxylic acid tert-butyl ester (2.44 g, 7.62 mmol) in DMF (10 mL) was added dropwise. The mixture was warmed to rt and stirred for 18 h. The mixture was diluted with CHCl3 (100 mL) and washed with water (100 mL). The organic layer was dried and concentrated to obtain the crude residue which was purified by FCC (EtOAc/hexanes) to give 1.50 g (55%) of a colorless oil. 1H NMR (CD3OD): 7.17 (d, J=8.2, 1H), 7.13-7.09 (m, 1H), 7.07 (d, J=3.2, 1H), 6.90 (d, J=6.9, 1H), 6.49 (d, J=3.2, 1H), 4.09 (t, J=7.1, 1H), 2.68-2.57 (m, 2H), 2.55 (s, 3H), 1.90-1.79 (m, 2H), 1.64-1.55 (m, 2H), 1.44 (s, 9H), 1.40-1.21 (m, 3H), 1.13-0.98 (m, 1H).

Workup

  1. washwashed with water (100 mL)
  2. customThe organic layer was dried
  3. concentrationconcentrated
  4. customto obtain the crude residue which
  5. customwas purified by FCC (EtOAc/hexanes)

Sources & evidence

ORD record
ord-f4a5f2bf414b48ad8de1a4bad8e841c5
Source dataset
uspto-grants-2011_12
Patent number
US08084466B2

Reaction notes

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