Tributylphosphine → 3-(4-(3-t-Butyldimethylsilyloxy-1-azetidinyl)-3-fluorophenyl)-5(R)-(isoxazol-3-yl-oxymethyl)oxazolidin-2-one

HRID 1167431Notes

Reaction equation

HRID 1167431 reaction equation
[Si:1]([O:8][CH:9]1[CH2:12][N:11]([C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:23][C@H:22]([CH2:24][OH:25])[O:21][C:20]3=[O:26])=[CH:15][C:14]=2[F:27])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].O[C:29]1[CH:33]=[CH:32][O:31][N:30]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>O1CCCC1>[Si:1]([O:8][CH:9]1[CH2:10][N:11]([C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:23][C@H:22]([CH2:24][O:25][C:29]4[CH:33]=[CH:32][O:31][N:30]=4)[O:21][C:20]3=[O:26])=[CH:15][C:14]=2[F:27])[CH2:12]1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 213565963-(4-(3-t-Butyldimethylsilyloxy-1-azetidinyl)-3-fluorophenyl)-5(R)-hydroxymethyloxazolidin-2-oneHCID 178516613HCID 178516613, compound

Product 1

HCID 699815973-(4-(3-t-Butyldimethylsilyloxy-1-azetidinyl)-3-fluorophenyl)-5(R)-(isoxazol-3-yl-oxymethyl)oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-(4-(3-t-Butyldimethylsilyloxy-1-azetidinyl)-3-fluorophenyl)-5(R)-hydroxymethyloxazolidin-2-one (WO 96/13502; 2.47 g, 6.25 mmol), 3-hydroxyisoxazole (580 mg, 6.86 mmol), and tributylphosphine (1.58 g, 7.8 mmol) were dissolved by stirring in dry tetrahydrofuran (100 ml) under nitrogen. The mixture was cooled in an ice-bath, and 1,1′-(azodicarbonyl)dipiperidine (1.96 g, 7.8 mmol) added dropwise over 10 minutes. The solution was stirred 18 hours, allowing the temperature to rise to ambient. Reduced azo compound was filtered off, and the solution evaporated to dryness and the residue triturated with ether. The residue was purified by chromatography on a silica flash column, eluting with a gradient from 50 to 75% EtOAc in isohexane. Relevant fractions were combined and evaporated to the product as an oil (1.31 g).

Workup

  1. temperatureThe mixture was cooled in an ice-bath
  2. filtrationReduced azo compound was filtered off
  3. customthe solution evaporated to dryness
  4. customthe residue triturated with ether
  5. customThe residue was purified by chromatography on a silica flash column
  6. washeluting with a gradient from 50 to 75% EtOAc in isohexane
  7. customevaporated to the product as an oil (1.31 g)

Sources & evidence

ORD record
ord-f888938a6a9e4456a370a053d7a26fed
Source dataset
uspto-grants-2003_09
Patent number
US06617339B1

Reaction notes

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