18-Crown-6 → HCID 178491286, compound

HRID 1689779Notes

Reaction equation

HRID 1689779 reaction equation
[CH3:1][O:2][C:3]1[CH:23]=[CH:22][C:6]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([CH:15]3[CH2:20][CH2:19][CH:18]([OH:21])[CH2:17][CH2:16]3)=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.C1OCCOCCOCCOCCOCCOC1.[K].Br[CH2:44][C:45]1[C:46]([C:53]2[C:58]([Cl:59])=[CH:57][CH:56]=[CH:55][C:54]=2[Cl:60])=[N:47][O:48][C:49]=1[CH:50]1[CH2:52][CH2:51]1>O1CCCC1.C(O)(C)(C)C>[CH:50]1([C:49]2[O:48][N:47]=[C:46]([C:53]3[C:58]([Cl:59])=[CH:57][CH:56]=[CH:55][C:54]=3[Cl:60])[C:45]=2[CH2:44][O:21][C@H:18]2[CH2:19][CH2:20][C@H:15]([C:12]3[CH:13]=[CH:14][C:9]([O:8][CH2:7][C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:23][CH:22]=4)=[CH:10][CH:11]=3)[CH2:16][CH2:17]2)[CH2:52][CH2:51]1

Participants

7

Reactant 4

HCID 2855718-Crown-6HCID 5462222PotassiumHCID 593693284-(Bromomethyl)-5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazoleHCID 669059354-[4-(4-Methoxy-benzyloxy)-phenyl]-cyclohexanol

Product 1

HCID 178491286HCID 178491286, compoundYield 74.1%

Reagents, catalysts & solvents 2

HCID 6386tert-ButanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

4-[4-(4-Methoxy-benzyloxy)-phenyl]-cyclohexanol (2.24 mmol, 700.00 mg) and 18-crown-6 (2.69 mmol, 710.70 mg) in tetrahydrofuran (10 mL) is treated with tert-butyl alcohol, potassium derivative (2.69 mmol, 2.69 mL; 1M in THF). The mixture is stirred for 30 minutes and 4-bromomethyl-5-cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazole (3.36 mmol, 1.17 g) is added. The mixture is stirred at room temperature for 5 minutes and heated to 40° C. for 1.5 h. Silica gel is added and the reaction mixture is concentrated under reduced pressure. The crude mixture is purified by silica gel flash chromatography eluting with a gradient of 10-60% EtOAc in hexanes. A second chromatography is performed on silica gel eluting with 0.5% EtOAc in DCM to yield the title compound (960 mg, 74%). MS m/z 577.9 (M+1).

Workup

  1. stirringThe mixture is stirred at room temperature for 5 minutes
  2. additionSilica gel is added
  3. concentrationthe reaction mixture is concentrated under reduced pressure
  4. customThe crude mixture is purified by silica gel flash chromatography
  5. washeluting with a gradient of 10-60% EtOAc in hexanes

Sources & evidence

ORD record
ord-bd1e5a668bed4016a0f96bf30bb36341
Source dataset
uspto-grants-2012_04
Patent number
US08153624B2

Reaction notes

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