m-Chloroperbenzoic acid → Di-tert-butyl (5-{2-fluoro-4-[(5R)-2-oxo-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-3-yl]phenyl}isoxazol-3-yl)methyl phosphate

HRID 456788Notes

Reaction equation

HRID 456788 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:15]2[CH2:19][C@H:18]([CH2:20][N:21]3[CH:25]=[CH:24][N:23]=[N:22]3)[O:17][C:16]2=[O:26])[CH:5]=[CH:6][C:7]=1[C:8]1[O:12][N:11]=[C:10]([CH2:13][OH:14])[CH:9]=1.[C:27]([O:31][P:32](N(CC)CC)[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:30])([CH3:29])[CH3:28].N1C=NN=N1.ClC1C=CC=C(C(OO)=[O:56])C=1.S(=O)(O)[O-].[Na+]>ClCCl>[P:32]([O:14][CH2:13][C:10]1[CH:9]=[C:8]([C:7]2[CH:6]=[CH:5][C:4]([N:15]3[CH2:19][C@H:18]([CH2:20][N:21]4[CH:25]=[CH:24][N:23]=[N:22]4)[O:17][C:16]3=[O:26])=[CH:3][C:2]=2[F:1])[O:12][N:11]=1)([O:31][C:27]([CH3:28])([CH3:29])[CH3:30])([O:33][C:34]([CH3:35])([CH3:36])[CH3:37])=[O:56]

Participants

7

Reactant 5

HCID 70297m-Chloroperbenzoic acidHCID 4251849Di-tert-butyl diethylphosphoramiditeHCID 10066998(5R)-3-{3-Fluoro-4-[3-(hydroxymethyl)isoxazol-5-yl]phenyl}-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-oneHCID 23665763Sodium BisulfiteHCID 178418441HCID 178418441, compound

Product 1

HCID 71205223Di-tert-butyl (5-{2-fluoro-4-[(5R)-2-oxo-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-3-yl]phenyl}isoxazol-3-yl)methyl phosphateYield 55%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(5R)-3-{3-Fluoro-4-[3-(hydroxymethyl)isoxazol-5-yl]phenyl}-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-one (Example 3, 0.1 g, 0.3 mmol) was suspended in dichloromethane (3 ml), and di-tert-butyl-N,N-diethylphosphoramidite (93 μl, 0.3 mmol) and 1H-tetrazole (35 mg, 0.5 mmol) were added sequentially. The mixture was stirred under nitrogen at room temperature for 1.5 hours. Solution was cooled to 0° C. and m-chloroperbenzoic acid (≈70%, 0.1 g, 0.4 mmol) was added. The reaction was stirred at 0° C. under nitrogen for 2 hours. After warming to room temperature, saturated sodium bisulfite (3 ml) was added and the mixture stirred for 5 minutes followed by dilution with dichloromethane (10 ml). After the layers were separated, the aqueous phase was extracted with dichloromethane (3×10 ml); the combined organics were washed with saturated sodium bicarbonate, and brine, and dried over sodium sulfate. The crude material was purified by chromatography (using a Jones Flashmaster) using 0–5% methanol in dichloromethane as eluent. Relevant fractions were combined giving 91 mg of the desired product as a white solid.

Workup

  1. temperatureSolution was cooled to 0° C.
  2. stirringThe reaction was stirred at 0° C. under nitrogen for 2 hours
  3. temperatureAfter warming to room temperature
  4. stirringthe mixture stirred for 5 minutes
  5. customAfter the layers were separated
  6. extractionthe aqueous phase was extracted with dichloromethane (3×10 ml)
  7. washthe combined organics were washed with saturated sodium bicarbonate, and brine
  8. dry with materialdried over sodium sulfate
  9. customThe crude material was purified by chromatography (

Sources & evidence

ORD record
ord-9f5e8849a4e741179ecfb5b49613b631
Source dataset
uspto-grants-2007_03
Patent number
US07186738B2

Reaction notes

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