5-Bromo-2-chlorobenzaldehyde → (5-Bromo-2-chloro-phenyl)-[6-(2,4-difluoro-phenylamino)-pyridin-3-yl]-methanol

HRID 896090Notes

Reaction equation

HRID 896090 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=2[F:16])=[N:6][CH:7]=1.[Li]CCCC.[Br:22][C:23]1[CH:24]=[CH:25][C:26]([Cl:31])=[C:27]([CH:30]=1)[CH:28]=[O:29]>C1COCC1.CCCCCC>[Br:22][C:23]1[CH:24]=[CH:25][C:26]([Cl:31])=[C:27]([CH:28]([C:2]2[CH:7]=[N:6][C:5]([NH:8][C:9]3[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=3[F:16])=[CH:4][CH:3]=2)[OH:29])[CH:30]=1

Participants

6

Reactant 3

HCID 106089255-Bromo-2-chlorobenzaldehydeHCID 22349574(5-Bromo-pyridin-2-yl)-(2,4-difluoro-phenyl)-amineHCID 178418339Butyllithium

Product 1

HCID 22349578(5-Bromo-2-chloro-phenyl)-[6-(2,4-difluoro-phenylamino)-pyridin-3-yl]-methanol

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

(5-Bromo-pyridin-2-yl)-(2,4-difluoro-phenyl)-amine (3 g; 10.5 mmol) is dissolved in THF (70 ml) and cooled to −78 C. nBuLi (14.5 ml of a 1.5M solution in hexane; 23 mmol) is added dropwise and the resulting yellow suspension stirred or 20 min. 5-Bromo-2-chlorobenzaldehyde in THF (6 ml) is added at −78 C. After 5 min at −78 C, the reaction mixture is warmed to −50 C, poured on water and extracted with TBME twice. The combined organic phases are dried over Na2SO4 and evaporated to dryness. Purification via chromatography (SiO2; acetone/hexanes 6/94>12/88) yields the title compound as orange viscuous oil, (2.58 g; 58%) which is used in the next step. b) (5-Bromo-2-chloro-phenyl)-[6-(2,4-difluoro-phenylamino)-pyridin-3-yl]-methanone

Workup

  1. temperaturecooled to −78 C
  2. addition23 mmol) is added dropwise
  3. waitAfter 5 min at −78 C
  4. temperaturethe reaction mixture is warmed to −50 C
  5. additionpoured on water
  6. extractionextracted with TBME twice
  7. dry with materialThe combined organic phases are dried over Na2SO4
  8. customevaporated to dryness
  9. customPurification via chromatography (SiO2; acetone/hexanes 6/94>12/88)

Sources & evidence

ORD record
ord-e0baec73d29840bfbd8462f3aa5cdda8
Source dataset
uspto-grants-2005_07
Patent number
US06919336B2

Reaction notes

Loading…