3-(4-(3(S)-(2-Methoxyethoxycarbonylamino)pyrrolidin-1-yl)-3-fluorophenyl)-5(R)-(N-(2,2,2-trichloroethyloxycarbonyl)isoxazol-3-ylaminomethyl)oxazolidin-2-one → 3-(4-(3(S)-(2-Methoxyethoxycarbonylamino)pyrrolidin-1-yl)-3-fluorophenyl)-5(S)-(isoxazol-3-ylaminomethyl)oxazolidin-2-one

HRID 8168Notes

Reaction equation

HRID 8168 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]([NH:8][C@H:9]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:24][C@H:23]([CH2:25][N:26]([C:35]4[CH:39]=[CH:38][O:37][N:36]=4)C(OCC(Cl)(Cl)Cl)=O)[O:22][C:21]3=[O:40])=[CH:16][C:15]=2[F:41])[CH2:10]1)=[O:7]>C(O)(=O)C.O.[Zn]>[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]([NH:8][C@H:9]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:24][C@H:23]([CH2:25][NH:26][C:35]4[CH:39]=[CH:38][O:37][N:36]=4)[O:22][C:21]3=[O:40])=[CH:16][C:15]=2[F:41])[CH2:10]1)=[O:7]

Participants

5

Reactant 1

HCID 695847543-(4-(3(S)-(2-Methoxyethoxycarbonylamino)pyrrolidin-1-yl)-3-fluorophenyl)-5(R)-(N-(2,2,2-trichloroethyloxycarbonyl)isoxazol-3-ylaminomethyl)oxazolidin-2-one

Product 1

HCID 695848763-(4-(3(S)-(2-Methoxyethoxycarbonylamino)pyrrolidin-1-yl)-3-fluorophenyl)-5(S)-(isoxazol-3-ylaminomethyl)oxazolidin-2-oneYield 48.6%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

3-(4-(3(S)-(2-Methoxyethoxycarbonylamino)pyrrolidin-1-yl)-3-fluorophenyl)-5(R)-(N-(2,2,2-trichloroethyloxycarbonyl)isoxazol-3-ylaminomethyl)oxazolidin-2-one (400 mg, 0.5 mM) was stirred in a mixture of acetic acid (10 ml) and water (2 ml). Zinc dust (203 mg, 3.1 mM) was added, and the mixture stirred 30 minutes at ambient temperature. The mixture was filtered through celite, and the residue after evaporation partitioned between ethyl acetate (10 ml) and aqueous sodium bicarbonate (15 ml). The organic phase was washed with sodium bicarbonate (2×15 ml), water (15 ml), dried (magnesium sulfate), and evaporated. The crude product was purified by chromatography on a 10 g Biotage silica column, eluting with a gradient from dichloromethane to ethyl acetate. Relevant fractions were combined to give the desired product (141 mg).

Workup

  1. filtrationThe mixture was filtered through celite
  2. customthe residue after evaporation
  3. custompartitioned between ethyl acetate (10 ml) and aqueous sodium bicarbonate (15 ml)
  4. washThe organic phase was washed with sodium bicarbonate (2×15 ml), water (15 ml)
  5. dry with materialdried (magnesium sulfate)
  6. customevaporated
  7. customThe crude product was purified by chromatography on a 10 g Biotage silica column
  8. washeluting with a gradient from dichloromethane to ethyl acetate

Sources & evidence

ORD record
ord-4d6e3d9e1bbd4dc7b675038819d674a7
Source dataset
uspto-grants-2006_08
Patent number
US07087629B2

Reaction notes

Loading…