Tetrahydrofuran → HCID 59201437, compound

HRID 451878Notes

Reaction equation

HRID 451878 reaction equation
C1(OC(=O)[CH2:9][CH2:10][C@@H:11]([CH2:27][O:28]S(C2C=CC(C)=CC=2)(=O)=O)[CH2:12][C@H:13]2[CH2:17][O:16][C:15]([CH3:19])([CH3:18])[N:14]2[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])CCCCC1.C[Mg]Br.[CH2:43]1[CH2:47]OC[CH2:44]1>>[CH3:44][C:43]1([CH3:47])[O:28][CH2:27][C@@H:11]([CH2:12][C@H:13]2[CH2:17][O:16][C:15]([CH3:19])([CH3:18])[N:14]2[C:20]([O:22][C:23]([CH3:25])([CH3:26])[CH3:24])=[O:21])[CH2:10][CH2:9]1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 59201488HCID 59201488, compoundHCID 178418573HCID 178418573, compoundHCID 178418689HCID 178418689, compound

Product 1

HCID 59201437HCID 59201437, compoundYield 78%

Conditions

Temperature
0 °C

Procedure

The (S)-tert-butyl 4-((R)-5-(cyclohexyloxy)-5-oxo-2-(tosyloxymethyl)pentyl)-2,2-dimethyloxazolidine-3-carboxylate (309 mg, 0.545 mmol, 1.0 equiv) was dissolved in 17 mL of THF and the solution cooled to 0° C. Methylmagnesiumbromide (3.0 M in THF, 1.64 mL, 3.0 equiv) was added via syringe. LC/MS analysis showed ca 15% conversion to the mono-tosylate. An additional 0.55 mL of MeMgBr solution was added and the mixture warmed to ambient and stirred overnight. LC/MS analysis showed complete conversion to the mono-tosylate. The mixture was heated to reflux for 24 hr. After this time, complete conversion to the cyclised product was observed. The mixture was cooled to ambient and quenched with water. The layers were separated and the organic layer washed with brine, dried over Na2SO4, filtered and evaporated. The pyran derivative was purified by flash chromatography on silica, (12 g), eluting with 0-41% EtOAc in hexanes. This afforded 138 g (78% yield) of (S)-tert-butyl 4-(((R)-6,6-dimethyl-tetrahydro-2H-pyran-3-yl)methyl)-2,2-dimethyloxazolidine-3-carboxylate as a clear syrup. MS ESI +ve m/z 350 (M+Na).

Workup

  1. temperaturethe mixture warmed
  2. temperatureThe mixture was heated
  3. temperatureto reflux for 24 hr
  4. temperatureThe mixture was cooled to ambient and
  5. customquenched with water
  6. customThe layers were separated
  7. washthe organic layer washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe pyran derivative was purified by flash chromatography on silica, (12 g)
  12. washeluting with 0-41% EtOAc in hexanes

Sources & evidence

ORD record
ord-d2181287a45f43b0b8b1827a9bc22f86
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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