Sodium Iodide → HCID 56599142, compound

HRID 1750121Notes

Reaction equation

HRID 1750121 reaction equation
BrC[CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]2[S:14][CH:13]=[N:12][C:11]=2[CH:15]=1.[Na+].[I-].[Cl:18][C:19]1[C:24]([Cl:25])=[CH:23][CH:22]=[CH:21][C:20]=1[CH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.C([O-])([O-])=O.[K+].[K+]>CC#N>[Cl:18][C:19]1[C:24]([Cl:25])=[CH:23][CH:22]=[CH:21][C:20]=1[CH:26]1[CH2:31][CH2:30][N:29]([CH2:3][CH2:4][CH2:5][O:6][C:7]2[CH:8]=[CH:9][C:10]3[S:14][CH:13]=[N:12][C:11]=3[CH:15]=2)[CH2:28][CH2:27]1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 17895683HCID 17895683, compoundHCID 68630196HCID 68630196, compound

Product 1

HCID 56599142HCID 56599142, compoundYield 62.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of intermediate 26 (218 mg, 0.8 mmol) and NaI (240 mg, 1.6 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 47 (320 mg, 1.2 mmol) and anhydrous K2CO3 (442 mg, 3.8 mmol) were added to the mixture. The resulting mixture was heated to reflux and stirred overnight. Precipitated crystals were filtered off and the filtrate was evaporated under reduced pressure. The residue was extracted with EtOAc. The combined EtOAc layers were washed with brine, dried over anhydrous Na2SO4, concentrated in vacuo and purified by flash chromatography on silica gel column (elution with DCM/MeOH=30:1) to give 5-(3-(4-(2,3-dichlorophenyl)piperidin-1-yl)propoxy)benzo[d]thiazole (compound 22) (211 mg, 56%). 1H NMR (300 MHz, CDCl3): δ 8.98 (s, 1H), 7.80 (d, J=8.7 Hz, 1H), 7.62 (d, J=3.0 Hz, 1H), 7.34-7.31 (m, 1H), 7.24-7.18 (m, 3H), 7.15-7.09 (m, 1H), 4.15 (t, J=5.7 Hz, 2H), 3.18-3.12 (m, 3H), 2.70-2.66 (m, 2H), 2.27-2.19 (m, 2H), 2.17-2.10 (m, 2H), 1.92-1.81 (m, 4H). HPLC: 99%, RT 2.622 min. MS (ESI) m/z 421.1 [M+H]+. mp: 114-116° C.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 30 min
  3. temperatureThe resulting mixture was heated
  4. temperatureto reflux
  5. customPrecipitated crystals
  6. filtrationwere filtered off
  7. customthe filtrate was evaporated under reduced pressure
  8. extractionThe residue was extracted with EtOAc
  9. washThe combined EtOAc layers were washed with brine
  10. dry with materialdried over anhydrous Na2SO4
  11. concentrationconcentrated in vacuo
  12. custompurified by flash chromatography on silica gel column (elution with DCM/MeOH=30:1)

Sources & evidence

ORD record
ord-9252cdc46f7046deae7afb74d81aadce
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

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