Dimethylformamide → 6-(2-Chloro-benzylamino)-2-fluoro-pyridine-3-carbaldehyde

HRID 1775151Notes

Reaction equation

HRID 1775151 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([NH:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[Cl:17])=[N:6][C:7]=1[F:8].C([Mg]Cl)(C)C.C([Li])(C)(C)C.CN(C)[CH:30]=[O:31]>O1CCCC1.O>[Cl:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[CH2:10][NH:9][C:5]1[N:6]=[C:7]([F:8])[C:2]([CH:30]=[O:31])=[CH:3][CH:4]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 57619357(5-Bromo-6-fluoro-pyridin-2-yl)-(2-chloro-benzyl)-amineHCID 178418306HCID 178418306, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 579631956-(2-Chloro-benzylamino)-2-fluoro-pyridine-3-carbaldehydeYield 93.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To (5-bromo-6-fluoro-pyridin-2-yl)-(2-chloro-benzyl)-amine (17, 1.85 g, 5.86 mmol) in 25.0 mL of tetrahydrofuran under an atmosphere of nitrogen at −78° C., isopropylmagnesium chloride (3.00 mL, 2.00 M in tetrahydrofuran, 6.00 mmol) was added over 10 minutes. After 50 minutes, tert-butyllithium (7.80 mL, 1.70 M in hexane, 13.3 mmol) was added over 5 minutes. After 20 minutes, N,N-dimethylformamide (1.09 mL, 14.0 mmol) was added and the reaction mixture stirred at −78° C. for 20 minutes, then brought to room temperature over 30 minutes. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography, eluting with 35% ethyl acetate in hexane. The appropriate fractions were combined and the solvents removed under vacuum to provide the desired compound (18, 1.45 g). MS (ESI) [M+H+]+=265.4.

Workup

  1. waitAfter 20 minutes
  2. waitbrought to room temperature over 30 minutes
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated under vacuum
  8. customThe resulting material was purified by silica gel column chromatography
  9. washeluting with 35% ethyl acetate in hexane
  10. customthe solvents removed under vacuum

Sources & evidence

ORD record
ord-075103f054cf4be98faf70e71c55d7fc
Source dataset
uspto-grants-2016_02
Patent number
US09260437B2

Reaction notes

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