1,1'-(Azodicarbonyl)dipiperidine → 5-(4-(5-Cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy)-2-methyl-phenyl)-thiophene-2-carboxylic acid methyl ester

HRID 250284Notes

Reaction equation

HRID 250284 reaction equation
[CH:1]1([C:4]2[O:8][N:7]=[C:6]([C:9]3[C:14]([Cl:15])=[CH:13][CH:12]=[CH:11][C:10]=3[Cl:16])[C:5]=2[CH2:17][OH:18])[CH2:3][CH2:2]1.[CH3:19][O:20][C:21]([C:23]1[S:24][C:25]([C:28]2[CH:33]=[CH:32][C:31](O)=[CH:30][C:29]=2[CH3:35])=[CH:26][CH:27]=1)=[O:22].C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1>C1(C)C=CC=CC=1>[CH3:19][O:20][C:21]([C:23]1[S:24][C:25]([C:28]2[CH:33]=[CH:32][C:31]([O:18][CH2:17][C:5]3[C:6]([C:9]4[C:10]([Cl:16])=[CH:11][CH:12]=[CH:13][C:14]=4[Cl:15])=[N:7][O:8][C:4]=3[CH:1]3[CH2:3][CH2:2]3)=[CH:30][C:29]=2[CH3:35])=[CH:26][CH:27]=1)=[O:22]

Participants

5

Reactant 3

HCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 45790382(5-Cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methanolHCID 574432865-(4-Hydroxy-2-methyl-phenyl)-thiophene-2-carboxylic acid methyl ester

Product 1

HCID 580883565-(4-(5-Cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy)-2-methyl-phenyl)-thiophene-2-carboxylic acid methyl esterYield 45.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To a solution of (5-cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-yl)-methanol (0.188 g, 0.66 mmol), 5-(4-hydroxy-2-methyl-phenyl)-thiophene-2-carboxylic acid methyl ester (0.15 g, 0.60 mmol), and tri-N-butyl-phosphine (0.16 g, 0.79 mmol) in toluene (2 mL) is added a solution of ADDP (0.2 g, 0.79 mmol) in 1 mL of toluene. The reaction is stirred overnight. The reaction mixture is partitioned between ethyl acetate and water and the layers are separated. The organic layer is washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to yield a crude oil. The oil is chromatographed using a gradient of 10% ethyl acetate in hexanes to 40% ethyl acetate in hexanes to yield the title compound (0.14 g, 41%). ES/MS m/e 514.0 (M+1).

Workup

  1. customThe reaction mixture is partitioned between ethyl acetate and water
  2. customthe layers are separated
  3. washThe organic layer is washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto yield a crude oil
  8. customThe oil is chromatographed

Sources & evidence

ORD record
ord-11ec63371a9043fba1638f1c68e218c1
Source dataset
uspto-grants-2011_01
Patent number
US07863302B2

Reaction notes

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