Water → HCID 86721445, compound

HRID 869594Notes

Reaction equation

HRID 869594 reaction equation
[O:1]=[C:2]([CH2:9][CH2:10][CH3:11])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].[H-].[Na+].Br[CH2:15][C:16]1[CH:35]=[CH:34][C:19]2/[C:20](=[C:30](/[CH3:33])\[C:31]#[N:32])/[C:21]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:22]=3[O:23][CH2:24][C:18]=2[CH:17]=1.O>C1COCC1>[C:31](/[C:30](=[C:20]1/[C:21]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:22]=2[O:23][CH2:24][C:18]2[CH:17]=[C:16]([CH2:15][CH:3]([C:2](=[O:1])[CH2:9][CH2:10][CH3:11])[C:4]([O:6][CH2:7][CH3:8])=[O:5])[CH:35]=[CH:34][C:19]/1=2)/[CH3:33])#[N:32]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 238498Ethyl 3-oxohexanoateHCID 86721333(E)-2-[8-(bromomethyl)-3-fluorodibenzo[b,e]oxepin-11(6H)-ylidene]propanenitrile

Product 1

HCID 86721445HCID 86721445, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

[step 1] Ethyl 3-oxohexanoate (883 mg, 5.58 mmol) was dissolved in THF (9 mL), sodium hydride (60% w/w, 190 mg, 4.75 mmol) was added, and the mixture was stirred at room temperature for 30 min. To the mixture was added dropwise a solution (9 mL) of (E)-2-[8-(bromomethyl)-3-fluorodibenzo[b,e]oxepin-11(6H)-ylidene]propanenitrile (1.0 g, 2.79 mmol) obtained in Reference Example 1 in tetrahydrofuran, and the mixture was stirred at room temperature overnight. Water was added to the mixture, and the mixture was extracted 3 times with ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1 v/v) to give (E)-ethyl 2-{[11-(1-cyanoethylidene)-3-fluoro-6,11-dihydrodibenzo[b,e]oxepin-8-yl]methyl}-3-oxohexanoate (1.19 g, 98%).

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. extractionthe mixture was extracted 3 times with ethyl acetate
  3. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1 v/v)

Sources & evidence

ORD record
ord-30f307f5c15542bfa4c29ec06803e8bc
Source dataset
uspto-grants-2015_03
Patent number
US08969345B2

Reaction notes

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