Tributylphosphine → (5S)-3-(3-fluoro-4-imidazol-1-yl-phenyl)-5-[(isoxazol-3-ylamino)methyl]oxazolidin-2-one

HRID 1582333

Reaction equation

HRID 1582333 reaction equation
[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([N:12]3[CH2:16][C@H:15]([CH2:17]O)[O:14][C:13]3=[O:19])=[CH:8][C:7]=2[F:20])[CH:5]=[CH:4][N:3]=[CH:2]1.ClC(Cl)(Cl)COC([NH:27][C:28]1[CH:32]=[CH:31][O:30][N:29]=1)=O.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>O1CCCC1>[O:30]1[CH:31]=[CH:32][C:28]([NH:27][CH2:17][C@@H:15]2[O:14][C:13](=[O:19])[N:12]([C:9]3[CH:10]=[CH:11][C:6]([N:1]4[CH:5]=[CH:4][N:3]=[CH:2]4)=[C:7]([F:20])[CH:8]=3)[CH2:16]2)=[N:29]1

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 12114192,2,2-Trichloroethyl isoxazol-3-ylcarbamateHCID 104927643-(3-Fluoro-4-(imidazol-1-yl)phenyl)-5(R)-hydroxymethyloxazolidin-2-one

Product 1

HCID 497417(5S)-3-(3-fluoro-4-imidazol-1-yl-phenyl)-5-[(isoxazol-3-ylamino)methyl]oxazolidin-2-oneYield 158.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

3-(4-Imidazol-1-yl-3-fluorophenyl)-5(R)-hydroxymethyloxazolidin-2-one (693 mg, 2.5 mM, see WO 96-23788) and 3-(2,2,2-trichloroethyloxycarbonylamino)isoxazole (649 mg, 2.5 mM) were suspended by stirring in dry tetrahydrofuran (25 ml) under nitrogen in an ice-bath. Tributylphosphine (808 mg, 4 mM) was added followed by 1,1′-(azodicarbonyl)dipiperidine (945 mg, 3.75 mM) dissolved in tetrahydrofuran (10 ml) over 10 minutes. The mixture was then stirred 18 hours, allowing the temperature to rise to ambient, then filtered, and the filter cake washed with tetrahydrofuran. The combined filtrates were evaporated and the residue purified by chromatography on a 20 g silica Mega Bond Elut® column, eluting with a gradient increasing in polarity from 0 to 5% methanol in dichloromethane. Relevant fractions were combined, evaporated, and the residue triturated with diethyl ether to give the desired product (1.36 g), contaminated with tributylphosphine oxide. NMR (DMSO-d6) δ: 3.95 (dd, 1H); 4.16 (dd, 1H); 4.26 (t, 1H); 4.41 (dd, 1H); 4.99 (dd, 1H); 5.08 (dd overlapping m, 2H); 6.89 (d, 1H); 7.10 (t, 1H); 7.44 (dd, 1H); 7.52 (d, 1H); 7.66 (t, 1H); 7.71 (dd, 1H); 7.98 (m, 1H); 8.90 (d, 1H). MS (ESP): 518 (MH+) for C19H15Cl3FN5O5

Workup

  1. filtrationthen filtered
  2. washthe filter cake washed with tetrahydrofuran
  3. customThe combined filtrates were evaporated
  4. customthe residue purified by chromatography on a 20 g silica Mega Bond Elut® column
  5. washeluting with
  6. temperaturea gradient increasing in polarity from 0 to 5% methanol in dichloromethane
  7. customevaporated
  8. customthe residue triturated with diethyl ether

Sources & evidence

ORD record
ord-30764d64bdad4abf86987b3e50f34368
Source dataset
uspto-grants-2004_05
Patent number
US06734200B1

Linked notes

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