1-Bromo-2-Chloroethane → 8-[3-(4-Methoxyphenyl)propyl]-5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-8-ol

HRID 656479Notes

Reaction equation

HRID 656479 reaction equation
[Mg].[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][CH2:12]Br)=[CH:6][CH:5]=1.BrCCCl.[CH:18]1[N:19]=[CH:20][N:21]2[CH2:26][CH2:25][CH2:24][C:23](=[O:27])[C:22]=12>C1COCC1>[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][CH2:12][C:23]2([OH:27])[CH2:24][CH2:25][CH2:26][N:21]3[CH:20]=[N:19][CH:18]=[C:22]23)=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 78491-Bromo-2-ChloroethaneHCID 5462224MagnesiumHCID 127769961-(3-Bromopropyl)-4-methoxybenzeneHCID 167520695H,6H,7H,8H-imidazo(1,5-a)pyridin-8-one

Product 1

HCID 669155018-[3-(4-Methoxyphenyl)propyl]-5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-8-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
70 °C

Procedure

A three-necked flask with dropping funnel and reflux condenser is charged with 285.000 mmol of magnesium turnings in 50 ml of THF. With stirring at an oil bath temperature of 70° C. a solution of 37.100 mmol of 3-(4-methoxyphenyl)bromopropane [57293-19-3] and 28.500 mmol 1-bromo-2-chloroethane in 40 ml of THF is added dropwise over 45 minutes. The mixture is subsequently stirred at 70° C. for 2 hours and then cooled to room temperature and the supernatant solution is transferred using a transfer cannula into a second three-necked flask, fitted with dropping funnel. The Grignard solution thus obtained is admixed dropwise, with ice-bath cooling, with 28.500 mmol of 6,7-dihydro-5H-imidazo[1,5-a]pyridin-8-one [426219-51-4] in solution in 50 ml of THF over 10 minutes. When addition is complete the reaction mixture is stirred at room temperature for 1 hour. It is quenched with 150 ml of 0.5M aqueous HCl and extracted with dichloromethane (3×). The combined organic phases are dried over sodium sulphate and evaporated. From the residue the title compound is obtained by means of flash chromatography (SiO2 60F) as an amber oil. Rf=0.08 (dichloromethane-ethanol=98:2); Rt=5.50.

Workup

  1. customA three-necked flask with dropping
  2. temperaturefunnel and reflux condenser
  3. additionis added dropwise over 45 minutes
  4. temperaturecooled to room temperature
  5. customfitted
  6. customThe Grignard solution thus obtained
  7. additionWhen addition
  8. stirringis stirred at room temperature for 1 hour
  9. customIt is quenched with 150 ml of 0.5M aqueous HCl
  10. extractionextracted with dichloromethane (3×)
  11. dry with materialThe combined organic phases are dried over sodium sulphate
  12. customevaporated

Sources & evidence

ORD record
ord-dc7f46a9f95b4b06a53fef6caf5e8863
Source dataset
uspto-grants-2011_12
Patent number
US08071774B2

Reaction notes

Loading…