18-Crown-6 → HCID 59369326, compound

HRID 1689791Notes

Reaction equation

HRID 1689791 reaction equation
[CH2:1]([O:3][C:4](=[O:19])[C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:17][CH2:16][CH2:15][CH:14]([OH:18])[CH2:13][CH2:12]2)=[CH:7][CH:6]=1)[CH3:2].C1OCCOCCOCCOCCOCCOC1.[K].Br[CH2:40][C:41]1[C:42]([C:49]2[C:54]([Cl:55])=[CH:53][CH:52]=[CH:51][C:50]=2[Cl:56])=[N:43][O:44][C:45]=1[CH:46]1[CH2:48][CH2:47]1>C(O)(C)(C)C.O1CCCC1>[CH2:1]([O:3][C:4](=[O:19])[C:5]1[CH:6]=[CH:7][C:8]([N:11]2[CH2:17][CH2:16][CH2:15][CH:14]([O:18][CH2:40][C:41]3[C:42]([C:49]4[C:50]([Cl:56])=[CH:51][CH:52]=[CH:53][C:54]=4[Cl:55])=[N:43][O:44][C:45]=3[CH:46]3[CH2:48][CH2:47]3)[CH2:13][CH2:12]2)=[CH:9][CH:10]=1)[CH3:2]

Participants

7

Reactant 4

HCID 2855718-Crown-6HCID 5462222PotassiumHCID 593693284-(Bromomethyl)-5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazoleHCID 669062524-(4-Hydroxy-azepan-1-yl)-benzoic acid ethyl ester

Product 1

HCID 59369326HCID 59369326, compound

Reagents, catalysts & solvents 2

HCID 6386tert-ButanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Anhydrous tetrahydrofuran (5 mL) is added at room temperature to a mixture of 4-(4-hydroxy-azepan-1-yl)-benzoic acid ethyl ester (364 mg, 1.38 mmol), 18-crown-6 (407 mg, 1.52 mmol) and tert-butyl alcohol, potassium derivative (178 mg, 1.52 mmol). The mixture is stirred for 5 minutes and then 4-bromomethyl-5-cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazole (480 mg, 1.38 mmol) is added. After 1.5 h, the solvent is removed and water is added. The aqueous phase is extracted with ethyl acetate. The organic layers are combined, dried over anhydrous sodium sulfate, filtered, and the solvent is removed under reduced pressure. The residue is purified via flash chromatography (40 g silica) eluting with a gradient of ethyl acetate/hexane (0% to 30%) to provide the title compound as a colorless waxy solid (203 mg, 28%). ES/MS m/z 529.0 (M+1).

Workup

  1. waitAfter 1.5 h
  2. customthe solvent is removed
  3. additionwater is added
  4. extractionThe aqueous phase is extracted with ethyl acetate
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customthe solvent is removed under reduced pressure
  8. customThe residue is purified via flash chromatography (40 g silica)
  9. washeluting with a gradient of ethyl acetate/hexane (0% to 30%)

Sources & evidence

ORD record
ord-c7eab4bc2f9d4f3aa4c0919cb2ffbe4e
Source dataset
uspto-grants-2012_04
Patent number
US08153624B2

Reaction notes

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