Trimethylsilyl triflate → N-{3-[3,5-difluoro-4-(4-oxo-3,4-dihydro-2H-pyridin-1-yl)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide

HRID 2213356Notes

Reaction equation

HRID 2213356 reaction equation
[NH2:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([N:9]2[CH2:13][CH:12]([CH2:14][NH:15][C:16](=[O:18])[CH3:17])[O:11][C:10]2=[O:19])=[CH:4][C:3]=1[F:20].O[CH2:22][C:23]1C2N=NNC=2[CH:26]=[CH:25][CH:24]=1.C[O:33]/C=C/C(O[Si](C)(C)C)=C.O([Si](C)(C)C)S(C(F)(F)F)(=O)=O.C([O-])(O)=O.[Na+]>CCO.C1COCC1>[F:20][C:3]1[CH:4]=[C:5]([N:9]2[CH2:13][CH:12]([CH2:14][NH:15][C:16](=[O:18])[CH3:17])[O:11][C:10]2=[O:19])[CH:6]=[C:7]([F:8])[C:2]=1[N:1]1[CH:26]=[CH:25][C:24](=[O:33])[CH2:23][CH2:22]1

Participants

8

Reactant 5

HCID 65367Trimethylsilyl triflateHCID 516892Sodium BicarbonateHCID 5366448trans-1-Methoxy-3-trimethylsilyloxy-1,3-butadieneHCID 21957324N-[3-(4-Amino-3,5-difluoro-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-acetamideHCID 178519450HCID 178519450, compound

Product 1

HCID 10451460N-{3-[3,5-difluoro-4-(4-oxo-3,4-dihydro-2H-pyridin-1-yl)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

N-[3-(4-Amino-3,5-difluoro-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide (0.745 g, 2.61 mmol) and hydroxymethylbenzotriazole (0.390 g, 2.61 mmol) are dissolved in dry EtOH (2.0 mL). This resulting solution is refluxed for 5 h, solvent is removed under vacuum, and the resulted aminal intermediate dried under high vacuum. Danishefsky's diene (75.3 mg, 0.43 mmol) is added with stirring to the suspension of above aminal intermediate (0.091 g, 0.21 mmol) in THF (3 mL) at 0° C., followed by trimethylsilyl triflate (ca. 20 mL). The resulting mixture is allowed to warm up to r.t. over 2 h. Sat. aq. NaHCO3 (10 mL) is added, and the mixture extracted with excess EtOAc several times. Solvent is removed under vacuum, and the crude product purified by PTLC (5% MeOH in DCM) followed by RP HPLC (gradient 0–60% of MeCN—water). MS (m/z): 366 [M+H]+. 1H NMR (300 MHz, CDCl3) δ 1.90 (s, 3H), 2.50–2.54 (m, 2H), 3.53–3.64 (m, 2H), 3.84–3.92 (m, 3H), 4.22 (t, 1H, J=9.3 Hz), 4.81–4.89 (m, 1H), 5.04 (d, 1H, J=7.8 Hz), 7.25–7.29 (m, 1H) 7.39–7.51 (m, 3H).

Workup

  1. temperatureThis resulting solution is refluxed for 5 h
  2. customsolvent is removed under vacuum
  3. dry with materialthe resulted aminal intermediate dried under high vacuum
  4. extractionthe mixture extracted with excess EtOAc several times
  5. customSolvent is removed under vacuum
  6. customthe crude product purified by PTLC (5% MeOH in DCM)

Sources & evidence

ORD record
ord-dcfba7b42f104e24a8219204ebbaff34
Source dataset
uspto-grants-2006_09
Patent number
US07105547B2

Reaction notes

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