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(Diethylamino)sulfur trifluoride → 4-Chloro-6-(1-fluoroethyl)pyrimidine

HRID 2401191
Notes
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Reaction equation

HRID 2401191 reaction equation
C(N(S(F)(F)[F:7])CC)C.[Cl:10][C:11]1[N:16]=[CH:15][N:14]=[C:13]([CH:17](O)[CH3:18])[CH:12]=1>C(Cl)Cl>[Cl:10][C:11]1[CH:12]=[C:13]([CH:17]([F:7])[CH3:18])[N:14]=[CH:15][N:16]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 838541011-(6-Chloropyrimidin-4-yl)ethanol2×

Product 1

HCID 838541004-Chloro-6-(1-fluoroethyl)pyrimidineYield 37.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

(Diethylamino)sulphur trifluoride (0.337 mL, 2.55 mmol) was added to DCM (13 mL), cooled to −78° C. and treated dropwise with a solution of 1-(6-chloro-4-pyrimidinyl)ethanol (Intermediate 20, 328 mg, 2.068 mmol) in DCM (4 mL) under argon. The resulting mixture was allowed to warm to room temperature and stirred for 4 hours. The reaction was quenched by adding water (5 mL) and extracted with DCM (×2). The DCM layers were separated, combined, dried under magnesium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography (Biotage SP4) eluting with a gradient of 0-25% ethyl acetate and iso-hexane. Product containing fractions were combined and evaporated under reduced pressure to give the title compound as a colourless oil (125 mg);

Workup

  1. temperatureto warm to room temperature
  2. customThe reaction was quenched
  3. additionby adding water (5 mL)
  4. extractionextracted with DCM (×2)
  5. customThe DCM layers were separated
  6. customdried under magnesium sulfate
  7. customevaporated under reduced pressure
  8. customThe residue was purified by column chromatography (Biotage SP4)
  9. washeluting with a gradient of 0-25% ethyl acetate and iso-hexane
  10. additionProduct containing fractions
  11. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-f943ac1ae97049739ab8e741e84fc117
Source dataset
uspto-grants-2014_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08796283B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes