Thiotepa → 8-Benzyloxy-2-methyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine

HRID 544464Notes

Reaction equation

HRID 544464 reaction equation
C1N(P(N2CC2)(N2CC2)=S)C1.[H-].[Na+].Cl.[OH:15][CH:16]1[CH2:21][CH2:20][CH2:19][N:18]2[CH:22]=[C:23]([CH3:25])[N:24]=[C:17]12.[CH2:26](Cl)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>CN(C=O)C>[CH2:26]([O:15][CH:16]1[CH2:21][CH2:20][CH2:19][N:18]2[CH:22]=[C:23]([CH3:25])[N:24]=[C:17]12)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

6

Reactant 4

HCID 5453ThiotepaHCID 7503Benzyl ChlorideHCID 24758Sodium hydrideHCID 139003388-Hydroxy-2-methyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine hydrochloride

Product 1

HCID 139003398-Benzyloxy-2-methyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

This reaction mixture (which contains the free base of the compound of StepA) was added stepwise to an ice cooled, stirred suspension of 1.02 g of 50%dispersion of sodium hydride. The resulting mixture is stirred 30 min. on an ice-water bath. To this cold suspension (which contains the alkoxide ofthe compound of Step A) there was added a solution of benzyl chloride (2.48g) in DMF. The resultant mixture was stirred in an ice bath for 5 min., at room temperature for 5 min., and then in a heating bath at 85°-90° C. for 1.5 hrs. The solvent was evaporated off at reduced pressure. To the residue there was added water and the mixture wasextracted three times with a 1:1 mixture of methylenechloride and ether. The combined extracts were washed with brine, dried over Na2SO4and the solvent evaporated at reduced pressure. The oily residue was chromatographed on silica gel, using a 1:1 mixture of acetone and methylene chloride as eluant. The title compound was obtained as a yellow oil with the following PMR spectrum (DMSO-d6): 2.08(3H,s); 1.7-2.2(4H,m); 3.65-4.1(2H,m); 4.42(IH, deformed triplet); 4.70(2H,s); 6.73(IH,s); 7.30(SH,s).

Workup

  1. temperaturecooled
  2. stirringThe resulting mixture is stirred 30 min. on an ice-water bath
  3. customThe solvent was evaporated off at reduced pressure
  4. additionTo the residue there was added water
  5. additionwith a 1:1 mixture of methylenechloride and ether
  6. washThe combined extracts were washed with brine
  7. customdried over Na2SO4and the solvent
  8. customevaporated at reduced pressure
  9. customThe oily residue was chromatographed on silica gel
  10. additiona 1:1 mixture of acetone and methylene chloride as eluant

Sources & evidence

ORD record
ord-3c053c13e5ca42cea76387c6c3d826bb
Source dataset
uspto-grants-1984_05
Patent number
US04450164

Reaction notes

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