Ammonium Chloride → HCID 86601403, compound

HRID 750794Notes

Reaction equation

HRID 750794 reaction equation
CS([C:5]1[N:10]=[C:9]([O:11][CH3:12])[C:8]([S:13]([C:16]([F:19])([F:18])[F:17])(=[O:15])=[O:14])=[C:7]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=2[Cl:27])[N:6]=1)(=O)=O.C([Li])CCC.[F:33][C:34]1[CH:35]=[C:36]([OH:41])[CH:37]=[CH:38][C:39]=1[F:40].[Cl-].[NH4+]>C1COCC1.C(Cl)Cl>[F:33][C:34]1[CH:35]=[C:36]([CH:37]=[CH:38][C:39]=1[F:40])[O:41][C:5]1[N:10]=[C:9]([O:11][CH3:12])[C:8]([S:13]([C:16]([F:19])([F:18])[F:17])(=[O:15])=[O:14])=[C:7]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=2[Cl:27])[N:6]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 759273,4-DifluorophenolHCID 69199317HCID 69199317, compoundHCID 178418339Butyllithium

Product 1

HCID 86601403HCID 86601403, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

2-Methylsulfonyl-4-methoxy-5-trifluoromethansulfonyl-6-[2,4-dichlorophenyl]pyrimidine (93 mg, 0.19 mmol), prepared as described in Reference Example 16, was suspended in THF (500 μL) in a vial fitted with a magnetic stir bar and rubber septum. The reaction mixture was cooled to −78° and 3,4-difluorolithium phenoxide, prepared by adding n-butyl lithium (100 μL, 2M solution) to 3,4-difluorophenol (26 mg, 0.19 mmol) in 500 μL THF at 0° C., was added by syringe. The mixture was brought to room temperature, stirred for 1 h and worked up by adding 2 mL DCM and 1 mL saturated ammonium chloride. The organic layer was separated, dried over MgSO4, filtered and the solvent removed under reduced pressure. HPLC analysis showed the product to be 95% pure and it was used in the next step without further purification. Rt=4.51 min. 1H-NMR 500 MHz (CDCl3): δ 4.12 (s, 3H), 7.02 (m, 1H), 7.15 (m, 1H), 7.20-7.45 (m, 3H), 7.54 (d, J=2 Hz).

Workup

  1. customa vial fitted with a magnetic stir bar
  2. temperatureThe reaction mixture was cooled to −78°
  3. additionwas added by syringe
  4. customwas brought to room temperature
  5. customThe organic layer was separated
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customthe solvent removed under reduced pressure
  9. customit was used in the next step without further purification

Sources & evidence

ORD record
ord-25888c783c434eaca43ed3f2e26ee883
Source dataset
uspto-grants-2008_07
Patent number
US07405221B2

Reaction notes

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