2,6-Lutidine → (E)-2-[8-(bromomethyl)-3-fluorodibenzo[b,e]oxepin-11(6H)-ylidene]propanenitrile

HRID 869620Notes

Reaction equation

HRID 869620 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2=[C:6]([CH:22]=1)[O:7][CH2:8][C:9]1[CH:19]=[C:18]([CH2:20]O)[CH:17]=[CH:16][C:10]=1/[C:11]/2=[C:12](/[CH3:15])\[C:13]#[N:14].CS(OS(C)(=O)=O)(=O)=O.[Br-:32].[Li+].N1C(C)=CC=CC=1C>C1COCC1.O>[Br:32][CH2:20][C:18]1[CH:17]=[CH:16][C:10]2/[C:11](=[C:12](/[CH3:15])\[C:13]#[N:14])/[C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:22][C:6]=3[O:7][CH2:8][C:9]=2[CH:19]=1

Participants

7

Reactant 4

HCID 79372,6-LutidineHCID 81560Methanesulfonic anhydrideHCID 82050Lithium BromideHCID 86721376HCID 86721376, compound

Product 1

HCID 86721333(E)-2-[8-(bromomethyl)-3-fluorodibenzo[b,e]oxepin-11(6H)-ylidene]propanenitrileYield 83.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

[step 6] (E)-2-[3-fluoro-8-(hydroxymethyl)dibenzo[b,e]oxepin-11(6H)-ylidene]propanenitrile (13.3 g, 45.0 mmol) obtained in step 5 was dissolved in THF (450 mL), methanesulfonic anhydride (19.6 g, 112.6 mmol), lithium bromide (23.5 g, 270.2 mmol) and 2,6-lutidine (31.5 mL, 270.2 mmol) were added, and the mixture was stirred at room temperature for 13 hr. To the mixture was added water (200 mL), and the mixture was extracted 3 times with ethyl acetate. The combined organic layers were washed with 1 mol/L hydrochloric acid (100 mL), saturated aqueous sodium hydrogen carbonate solution (100 mL) and saturated brine (100 mL), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol=100/0 v/v-97/3 v/v) to give the title compound (13.4 g, 83%).

Workup

  1. extractionthe mixture was extracted 3 times with ethyl acetate
  2. washThe combined organic layers were washed with 1 mol/L hydrochloric acid (100 mL), saturated aqueous sodium hydrogen carbonate solution (100 mL) and saturated brine (100 mL)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (chloroform/methanol=100/0 v/v-97/3 v/v)

Sources & evidence

ORD record
ord-d3207515a7074932860656d4d010e2b8
Source dataset
uspto-grants-2015_03
Patent number
US08969345B2

Reaction notes

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