Sodium hydride → HCID 23298202, compound

HRID 1953456Notes

Reaction equation

HRID 1953456 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([CH:12]([C:14]([F:17])([F:16])[F:15])[OH:13])=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.[H-].[Na+].[F:20][C:21]1[CH:22]=[N:23][C:24](S(C)(=O)=O)=[N:25][CH:26]=1>O1CCCC1>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([CH:12]([O:13][C:24]3[N:25]=[CH:26][C:21]([F:20])=[CH:22][N:23]=3)[C:14]([F:17])([F:15])[F:16])=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 5663795-Fluoro-2-methylsulfonylpyrimidineHCID 23298198HCID 23298198, compound

Product 1

HCID 23298202HCID 23298202, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

7-Chloro-α-(trifluoromethyl)-4-quinolinemethanol (0.25 g, 0.96 mmol) was dissolved in 5 ml of tetrahydrofuran in a oven dried, nitrogen swept 25 ml round bottomed flask and the resulting solution was cooled to 0° C. under nitrogen. With stirring, NaH (0.042 g, 1.1 mmol, 60% dispersion in mineral oil) was added all at once. After 15 minutes, 5-fluoro-2-(methylsulfonyl) pyrimidine (0.17 g, 0.96 mmol) was added dropwise via syringe as a solution in tetrahydrofuran (2.5 ml) over 5 minutes. An additional 2 ml of tetrahydrofuran was used to rinse the flask containing the sulfone and the syringe. The milky solution was allowed to warm to room temperature and stir for 15 hours by which time thin layer chromatography (hexanes:ethyl acetate/1:1) indicated complete consumption of the starting materials. The reaction mixture was partitioned between water and ethyl acetate, the layers separated and the aqueous layer extracted with an additional portion of ethyl acetate. The combined organic layers were dried (MgSO4) filtered and concentrated to dryness. Purification by flash silica gel chromatography (hexanes:ethyl acetate/2:1) provided 7-chloro-4-[2,2,2-trifluoro-1-[(5-fluoro-2-pyrimidinyl) oxy]ethyl]quinoline (0.32 g, 94%) as a white solid. An analytical sample was prepared by recrystallization from hexane. (mp 92° C.).

Workup

  1. customdried
  2. washto rinse the flask
  3. additioncontaining the sulfone
  4. temperatureto warm to room temperature
  5. stirringstir for 15 hours by which time thin layer chromatography (hexanes:ethyl acetate/1:1)
  6. customconsumption of the starting materials
  7. customThe reaction mixture was partitioned between water and ethyl acetate
  8. customthe layers separated
  9. extractionthe aqueous layer extracted with an additional portion of ethyl acetate
  10. dry with materialThe combined organic layers were dried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated to dryness
  13. customPurification by flash silica gel chromatography (hexanes:ethyl acetate/2:1)

Sources & evidence

ORD record
ord-0b8755ef4a7043e4a049f74d1e0cd446
Source dataset
uspto-grants-2000_09
Patent number
US06117884

Reaction notes

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