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Sodium hydride → 4-Chloro-2-[(2,3-difluorophenyl)methylthio]-6-{(1R)-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethoxy}pyrimidine

HRID 1024905
Notes
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Reaction equation

HRID 1024905 reaction equation
[CH3:1][C:2]1([CH3:10])[O:6][C@@H:5]([C@H:7]([OH:9])[CH3:8])[CH2:4][O:3]1.[H-].[Na+].[Cl:13][C:14]1[CH:19]=[C:18](Cl)[N:17]=[C:16]([S:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:24]=2[F:30])[N:15]=1>C1COCC1>[Cl:13][C:14]1[CH:19]=[C:18]([O:9][C@@H:7]([C@H:5]2[CH2:4][O:3][C:2]([CH3:10])([CH3:1])[O:6]2)[CH3:8])[N:17]=[C:16]([S:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:24]=2[F:30])[N:15]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 12241285(1R)-1-[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]ethanol2×HCID 859280374,6-Dichloro-2-((2,3-difluorobenzyl)thio)pyrimidine

Product 1

HCID 866198804-Chloro-2-[(2,3-difluorophenyl)methylthio]-6-{(1R)-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethoxy}pyrimidine

Reagents, catalysts & solvents 1

HCID 8028
Tetrahydrofuran
Solvent

Procedure

To a solution of (1R)-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethanol (the product of step iv) (0.24 g) in dry THF (10 mL) at 0° C. was added in portions sodium hydride (91 mg as 60% dispersion in mineral oil) followed in portions by 4,6-dichloro-2-[(2,3-difluorobenzyl)thio]pyrimidine (the product of example 1 step ii) (0.50 g). The reaction mixture was stirred at room temperature for 48 h then quenched with saturated aqueous ammonium chloride (10 mL) and diluted with ethyl acetate. The layers were separated and the aqueous layer extracted with further ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography on silica gel using EtOAc/isohexane (1:19 to 1:9 gradient) as eluent to give the subtitle compound as a pale yellow solid. Yield: 0.42 g.

Workup

  1. customthen quenched with saturated aqueous ammonium chloride (10 mL)
  2. additiondiluted with ethyl acetate
  3. customThe layers were separated
  4. extractionthe aqueous layer extracted with further ethyl acetate
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-7fc14a4255c0434fa00b79ba11f9893f
Source dataset
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08722883B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes