Potassium Carbonate → 1-{2-[6-(Benzothiazol-2-yloxy)-benzofuran-3-yl]-ethyl}-piperidine-4-carboxylic acid ethyl ester

HRID 1947531Notes

Reaction equation

HRID 1947531 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[O:10][C:11]1[CH:26]=[CH:25][C:14]2[C:15]([CH2:18][CH2:19]OS(C)(=O)=O)=[CH:16][O:17][C:13]=2[CH:12]=1.C([O-])([O-])=O.[K+].[K+].[NH:33]1[CH2:43][CH2:42][CH:36]([C:37]([O:39][CH2:40][CH3:41])=[O:38])[CH2:35][CH2:34]1>CC#N>[CH2:40]([O:39][C:37]([CH:36]1[CH2:42][CH2:43][N:33]([CH2:19][CH2:18][C:15]2[C:14]3[CH:25]=[CH:26][C:11]([O:10][C:2]4[S:1][C:5]5[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=5[N:3]=4)=[CH:12][C:13]=3[O:17][CH:16]=2)[CH2:34][CH2:35]1)=[O:38])[CH3:41]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 70770Ethyl 4-piperidinecarboxylateHCID 59577553Methanesulfonic acid 2-[6-(benzothiazol-2-yloxy)-benzofuran-3-yl]-ethyl ester

Product 1

HCID 498340941-{2-[6-(Benzothiazol-2-yloxy)-benzofuran-3-yl]-ethyl}-piperidine-4-carboxylic acid ethyl esterYield 47.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

To a suspension of methanesulfonic acid 2-[6-(benzothiazol-2-yloxy)-benzofuran-3-yl]-ethyl ester (200 mg, 0.5 mmol) and K2CO3 (78 mg, 0.6 mmol) in MeCN (5.2 mL) was added ethyl isonipecotate (0.08 mL, 0.5 mmol) and the reaction mixture was heated (70° C., 48 h). The reaction mixture was filtered, concentrated in vacuo and the resulting residue was partitioned between EtOAc and brine (20 mL each). The organic layer was dried, filtered and concentrated in vacuo. The resulting residue was purified by silica gel flash chromatography using EtOAc:hexane (20-80%) to provide the title compound as a clear oil (108 mg, 47%). MS (ESI): mass calcd. for C25H26N2O4S, 450.6; m/z found, 451.2 [M+H]+. 1H NMR (500 MHz, CDCl3): 7.43 (d, J=8.5, 1H), 7.65 (d, J=8.0, 1H), 7.58 (d, J=8.5, 1H), 7.54 (s, 1H), 7.51 (d, J=1.5, 1H), 7.39-7.36 (m, 1H), 7.27-7.24 (m, 2H), 4.14 (q, J=7.0, 2H), 2.98 (d, J=11.5, 2H), 2.89-2.85 (m, 2H), 2.69-2.66 (m, 2H), 2.34-2.29 (m, 1H), 2.14-2.10 (m, 2H), 1.96-2.94 (m, 2H), 1.85-1.77 (m, 2H), 1.26 (t, J=7.0, 3H).

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationconcentrated in vacuo
  3. customthe resulting residue was partitioned between EtOAc and brine (20 mL each)
  4. customThe organic layer was dried
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-c62e552c64ae41afb74ae3e2f9ead455
Source dataset
uspto-grants-2013_03
Patent number
US08399465B2

Reaction notes

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