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

HRID 2388862Notes

Reaction equation

HRID 2388862 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-24eee75963e94f70b0303ad6d16ca532
Source dataset
uspto-grants-2012_09
Patent number
US08269002B2

Reaction notes

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