Hydrochloric Acid → 1-(1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-4-yl)ethanone

HRID 475109Notes

Reaction equation

HRID 475109 reaction equation
Br[C:2]1[C:10]2[N:9]=[CH:8][N:7]([CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][O:12]3)[C:6]=2[CH:5]=[CH:4][CH:3]=1.C([Sn](CCCC)(CCCC)[C:22]([O:24]CC)=[CH2:23])CCC.[O-]P([O-])([O-])=O.[K+].[K+].[K+].Cl>CN1C(=O)CCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[O:12]1[CH2:13][CH2:14][CH2:15][CH2:16][CH:11]1[N:7]1[C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([C:22](=[O:24])[CH3:23])[C:10]=2[N:9]=[CH:8]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 62657Potassium Phosphate, TribasicHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 712721864-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole

Product 1

HCID 712723901-(1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-4-yl)ethanoneYield 59%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole (1.6 g, 6 mmol), tributyl(1-ethoxyvinyl)stannane (2.4 g, 6 mmol), Pd(PPh3)4 (0.7 g, 0.6 mmol), K3PO4 (2.5 g, 12 mmol) in NMP (10 mL) was heated at 80° C. for 6 h. The mixture was cooled to RT, water was added and the mixture was extracted with EtOAc (50 mL×3). HCl (1.0 eq) was added to the combined extract and the resulting mixture was stirred for 30 min. The pH of the mixture was adjusted to ˜8 by addition of aqueous NH4OH solution (35%). The aqueous phase was extracted with EtOAc (50 mL×3). The combined extracts were dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by SiO2 chromatography eluting with petroleum ether:EtOAc (10:1) to afford 1-(1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-4-yl)ethanone as a gray solid (0.8 g, 59%). MS (ESI): m/z=245.1 [M+1]+.

Workup

  1. temperatureThe mixture was cooled to RT
  2. extractionthe mixture was extracted with EtOAc (50 mL×3)
  3. extractioncombined extract
  4. additionThe pH of the mixture was adjusted to ˜8 by addition of aqueous NH4OH solution (35%)
  5. extractionThe aqueous phase was extracted with EtOAc (50 mL×3)
  6. dry with materialThe combined extracts were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by SiO2 chromatography
  10. washeluting with petroleum ether:EtOAc (10:1)

Sources & evidence

ORD record
ord-a679443a53bd4f8ea40430724526d1c0
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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