2,5-Dibromopyridine → HCID 59643333, compound

HRID 2251524Notes

Reaction equation

HRID 2251524 reaction equation
[CH3:1][C:2]([O:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][CH2:17][NH:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=2)=[CH:12][CH:11]=1)([CH3:8])[C:3]([O:5][CH2:6][CH3:7])=[O:4].Br[C:31]1[CH:36]=[CH:35][C:34]([Br:37])=[CH:33][N:32]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[Br:37][C:34]1[CH:35]=[CH:36][C:31]([N:18]([CH2:19][C:20]2[CH:21]=[CH:22][C:23]([C:26]([F:27])([F:28])[F:29])=[CH:24][CH:25]=2)[CH2:17][CH2:16][C:13]2[CH:14]=[CH:15][C:10]([O:9][C:2]([CH3:1])([CH3:8])[C:3]([O:5][CH2:6][CH3:7])=[O:4])=[CH:11][CH:12]=2)=[N:32][CH:33]=1

Participants

5

Reactant 3

HCID 693532,5-DibromopyridineHCID 81531Diisopropylethylamine2×HCID 59643115HCID 59643115, compound

Product 1

HCID 59643333HCID 59643333, compoundYield 18.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of ethyl 2-methyl-2-[4-(2-{[4-(trifluoromethyl)benzyl]amino}ethyl)phenoxy]propanoate (3 g; 7.3 mmol) in 7 ml of dioxane was treated under nitrogen with 2,5-dibromopyridine (1.9 g; 8.1 mmol) and DIEA (1.4 ml; 8.1 mmol) and heated in a pressure tube for 2 days at 210C. Upon cooling, additional DIEA (1.4 ml) was added and heated 2 more days. Upon cooling, the reaction mixture was partitioned between ethyl acetate and 0.5N HCl. The organic phase was washed with 0.5N HCl and saturated brine, dried over sodium sulfate and concentrated. Purification by silica gel chromatography using an ethyl acetate-hexane gradient (5–60%) afforded the title compound (0.75 g; 18% yield).

Workup

  1. temperatureUpon cooling
  2. temperatureheated 2 more days
  3. temperatureUpon cooling
  4. customthe reaction mixture was partitioned between ethyl acetate and 0.5N HCl
  5. washThe organic phase was washed with 0.5N HCl and saturated brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-a7b334ceef544331852cb738416c0d21
Source dataset
uspto-grants-2008_01
Patent number
US07319104B2

Reaction notes

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