P,P-Diphenylphosphinic azide → 3-[5-(1-Azido-ethyl)-4-methyl-thiophen-2-yl]-5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazole

HRID 2045952Notes

Reaction equation

HRID 2045952 reaction equation
C1(P([N:15]=[N+:16]=[N-:17])(C2C=CC=CC=2)=O)C=CC=CC=1.N12CCCC=C1CCCCN2.[Cl:29][C:30]1[CH:31]=[C:32]([C:37]2([C:51]([F:54])([F:53])[F:52])[O:41][N:40]=[C:39]([C:42]3[S:46][C:45]([CH:47](O)[CH3:48])=[C:44]([CH3:50])[CH:43]=3)[CH2:38]2)[CH:33]=[C:34]([Cl:36])[CH:35]=1>C1(C)C=CC=CC=1>[N:15]([CH:47]([C:45]1[S:46][C:42]([C:39]2[CH2:38][C:37]([C:32]3[CH:31]=[C:30]([Cl:29])[CH:35]=[C:34]([Cl:36])[CH:33]=3)([C:51]([F:54])([F:53])[F:52])[O:41][N:40]=2)=[CH:43][C:44]=1[CH3:50])[CH3:48])=[N+:16]=[N-:17]

Participants

5

Reactant 3

HCID 199401P,P-Diphenylphosphinic azideHCID 9834010Diazabicyclo[5.4.0]undec-7-eneHCID 665872011-{5-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophen-2-yl}-ethanol

Product 1

HCID 866812913-[5-(1-Azido-ethyl)-4-methyl-thiophen-2-yl]-5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazole

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Diphenylphosphoryl azide (0.53 ml) and diazabicyclo-[5.4.0]-undec-7-ene (DBU, 0.40 ml) is added to a solution of 1-{5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophen-2-yl}-ethanol (0.87 g) in toluene (9 ml). After 19 hours at room temperature, the reaction is quenched with a saturated aqueous solution of NH4Cl in water. The reaction mixture is extracted three times with ethyl acetate. The organic phases are combined, dried over MgSO4 and concentrated in vacuo. The crude product is purified on a semi-preparative HPLC to yield 3-[5-(1-azido-ethyl)-4-methyl-thiophen-2-yl]-5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazole (0.64 g) as a yellow oil. MS (HPLC/MS): 449 (MH+). Retention time: 2.45 min.

Workup

  1. customthe reaction is quenched with a saturated aqueous solution of NH4Cl in water
  2. extractionThe reaction mixture is extracted three times with ethyl acetate
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe crude product is purified on a semi-preparative HPLC

Sources & evidence

ORD record
ord-110771fc591b4c11be586642b342b5ab
Source dataset
uspto-grants-2013_11
Patent number
US08592418B2

Reaction notes

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