Cesium carbonate → 4-Benzyloxy-1-[2-(4-hydroxymethyl-phenyl)-ethyl]-1H-pyridin-2-one

HRID 564040Notes

Reaction equation

HRID 564040 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][NH:12][C:11](=[O:15])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.I[CH2:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][OH:26])=[CH:21][CH:20]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([CH2:25][OH:26])=[CH:21][CH:20]=2)[C:11](=[O:15])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 36077244-Benzyloxy-2(1H)-pyridoneHCID 18402547[4-(2-Iodo-ethyl)-phenyl]-methanol

Product 1

HCID 670067844-Benzyloxy-1-[2-(4-hydroxymethyl-phenyl)-ethyl]-1H-pyridin-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 13.0 g (64.6 mmol) 4-benzyloxy-1H-pyridin-2-one, 23.7 g (90.4 mmol) [4-(2-iodoethyl)-phenyl]-methanol (preparation 1b) and 63.1 g (194 mmol) cesium carbonate in 55 mL of DMF is stirred overnight at RT. The reaction mixture is heated to 70° C., filtered through a pad of celite which is washed with hot DMF. The solvent is removed almost completely. After cooling to RT, MeOH is added, the precipitate is filtered, washed with EtOAc and water and is dried in vacuo at 40° C. (fraction A). MeOH is removed in vacuo, the residue is redissolved in DMF and purified by reverse HPLC (Zorbax stable bond, C18; water (0.1% formic acid)/acetonitrile 95:5 to 10:90) to give fraction B, which is combined with fraction A.

Workup

  1. temperatureThe reaction mixture is heated to 70° C.
  2. filtrationfiltered through a pad of celite which
  3. washis washed with hot DMF
  4. customThe solvent is removed almost completely
  5. temperatureAfter cooling to RT
  6. additionMeOH is added
  7. filtrationthe precipitate is filtered
  8. washwashed with EtOAc and water
  9. customis dried in vacuo at 40° C. (fraction A)
  10. customMeOH is removed in vacuo
  11. dissolutionthe residue is redissolved in DMF
  12. custompurified by reverse HPLC (Zorbax stable bond, C18; water (0.1% formic acid)/acetonitrile 95:5 to 10:90)
  13. customto give fraction B, which

Sources & evidence

ORD record
ord-512e6f3562e140c281b20eb1a76e1083
Source dataset
uspto-grants-2011_11
Patent number
US08067590B2

Reaction notes

Loading…