Bis(2-oxo-3-oxazolidinyl)phosphinic chloride → (3S)-ethyl 1-(2-hydroxy-2-(4-(5-(3-(pyridin-2-yl)-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylate

HRID 1948485Notes

Reaction equation

HRID 1948485 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[C:11]([C:12]([F:15])([F:14])[F:13])=[C:10]([C:16]([OH:18])=O)[O:9][N:8]=1.[OH:19][CH:20]([C:33]1[CH:38]=[CH:37][C:36](/[C:39](=[N:41]\O)/[NH2:40])=[CH:35][CH:34]=1)[CH2:21][N:22]1[CH2:27][CH2:26][CH2:25][C@H:24]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:23]1.C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>CN(C=O)C.C(OCC)(=O)C>[OH:19][CH:20]([C:33]1[CH:38]=[CH:37][C:36]([C:39]2[N:41]=[C:16]([C:10]3[O:9][N:8]=[C:7]([C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=4)[C:11]=3[C:12]([F:13])([F:14])[F:15])[O:18][N:40]=2)=[CH:35][CH:34]=1)[CH2:21][N:22]1[CH2:27][CH2:26][CH2:25][C@H:24]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:23]1

Participants

7

Reactant 4

HCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 2724141Tetrabutylammonium FluorideHCID 583741783-(Pyridin-2-yl)-4-(trifluoromethyl)isoxazole-5-carboxylic acidHCID 178472508HCID 178472508, compound

Product 1

HCID 86656388(3S)-ethyl 1-(2-hydroxy-2-(4-(5-(3-(pyridin-2-yl)-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 3-(pyridin-2-yl)-4-(trifluoromethyl)isoxazole-5-carboxylic acid, Int-IV (45 mg, 0.174 mmol), (3S)-ethyl 1-(2-hydroxy-2-(4-((E)-N′-hydroxycarbamimidoyl)phenyl)ethyl)piperidine-3-carboxylate (70 mg, 0.209 mmol), and BOP-Cl (53 mg, 0.208 mmol) in DMF (5 mL) was added TEA (0.073 mL, 0.523 mmol). The reaction mixture was stirred at room temperature for 2 hr then TBAF (0.174 mL, 0.174 mmol) was added. Next, the reaction mixture was stirred for 3 days. The reaction mixture was diluted with ethyl acetate and washed with saturated NaCl. The organic layer was dried with MgSO4, filtered, and concentrated. The crude residue was purified by a silica gel cartridge using an EtOAc/hexanes gradient to yield 37 mg of (3S)-ethyl 1-(2-hydroxy-2-(4-(5-(3-(pyridin-2-yl)-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylate.

Workup

  1. stirringNext, the reaction mixture was stirred for 3 days
  2. washwashed with saturated NaCl
  3. dry with materialThe organic layer was dried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified by a silica gel cartridge

Sources & evidence

ORD record
ord-5525815ff9664e28ab42ac12f433fa44
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

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