Dimethylformamide → HCID 59593345, compound

HRID 1775148Notes

Reaction equation

HRID 1775148 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=2)=[N:6][CH:7]=1.C([Li])(C)(C)C.CN(C)[CH:24]=[O:25].[Cl-].[NH4+]>O1CCCC1>[Cl:16][C:13]1[CH:14]=[CH:15][C:10]([CH2:9][NH:8][C:5]2[N:6]=[CH:7][C:2]([CH:24]=[O:25])=[CH:3][CH:4]=2)=[CH:11][CH:12]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 975849HCID 975849, compoundHCID 178418306HCID 178418306, compound2×

Product 1

HCID 59593345HCID 59593345, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

(5-Bromo-pyridin-2-yl)-(4-chloro-benzyl)-amine (11, 3.81 g, 13 mmol) was dissolved in 150 mL of tetrahydrofuran at −78° C. under an atmosphere of nitrogen and tert-butyllithium (7.6 mL, 1.7 M in hexane) was added dropwise. After 30 minutes additional tert-butyllithium (16 mL, 1.7 M in hexane) was added dropwise and the reaction was stirred for 1.5 hours at −78° C. N,N-Dimethylformamide (2.4 mL, 31 mmol) was added and the mixture was stirred for 1.5 hours at −78° C., then allowed to warm up to room temperature for 1 hour. The reaction was poured into aqueous ammonium chloride and extracted with ethyl acetate. The organic portion was dried over anhydrous sodium sulfate and concentrated. The desired compound was crystallized from a mixture of ether in ethyl acetate. The remaining material was purified with silica gel chromatography eluting with ethyl acetate and hexane to provide additional compound (12, 2.7 g, 85%).

Workup

  1. stirringthe mixture was stirred for 1.5 hours at −78° C.
  2. temperatureto warm up to room temperature for 1 hour
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic portion was dried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customThe desired compound was crystallized from a mixture of ether in ethyl acetate
  7. customThe remaining material was purified with silica gel chromatography
  8. washeluting with ethyl acetate and hexane
  9. customto provide additional compound (12, 2.7 g, 85%)

Sources & evidence

ORD record
ord-6ab176a8b5f04e87a1f4644a5a95ca15
Source dataset
uspto-grants-2016_02
Patent number
US09260437B2

Reaction notes

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