Ethylene Glycol → 2-({6-Chloro-2-[(2,3-difluorobenzyl)thio]pyrimidin-4-yl)oxy}ethanol

HRID 1024988Notes

Reaction equation

HRID 1024988 reaction equation
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([S:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[C:12]=2[F:18])[N:3]=1.FC1C(F)=CC=CC=1CSC1N=C(NS(N2CCC2)(=O)=O)C=C([O:43][CH:44](CO)[CH2:45][OH:46])N=1.C(O)CO.[H-].[Na+]>C1COCC1>[Cl:8][C:6]1[N:5]=[C:4]([S:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[C:12]=2[F:18])[N:3]=[C:2]([O:43][CH2:44][CH2:45][OH:46])[CH:7]=1

Participants

6

Reactant 4

HCID 174Ethylene GlycolHCID 24758Sodium hydrideHCID 11698344N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-[2-hydroxy-1-(hydroxymethyl)ethoxy]-4-pyrimidinyl]-1-azetidinesulfonamideHCID 859280374,6-Dichloro-2-((2,3-difluorobenzyl)thio)pyrimidine

Product 1

HCID 866198902-({6-Chloro-2-[(2,3-difluorobenzyl)thio]pyrimidin-4-yl)oxy}ethanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4,6-dichloro-2-[(2,3-difluorobenzyl)thio]pyrimidine ((the product of example 1 step 5 g) and ethylene glycol (1.517 g) in THF (100 ml) was added NaH (1.3 g) slowly and the reaction was then allowed to stir overnight at RT. The reaction mixture was then partitioned between EtOAc (200 ml) and H2O (200 ml). The organics were separated and the aqueous layer was re-extracted with EtOAc (2×200 ml). Organics were combined, dried (MgSO4) and reduced in vacuo and the resulting residue was purified by column chromatography on silica gel 10% EtOAc/90% iso-Hex to give the subtitle compound as a clear oil. Yield: 2.4 g

Workup

  1. customThe reaction mixture was then partitioned between EtOAc (200 ml) and H2O (200 ml)
  2. customThe organics were separated
  3. extractionthe aqueous layer was re-extracted with EtOAc (2×200 ml)
  4. dry with materialdried (MgSO4)
  5. customthe resulting residue was purified by column chromatography on silica gel 10% EtOAc/90% iso-Hex

Sources & evidence

ORD record
ord-a69802f938ec46d2ac22f667d0313096
Source dataset
uspto-grants-2014_05
Patent number
US08722883B2

Reaction notes

Loading…