HCID 59201637, compound → HCID 59201552, compound

HRID 451880Notes

Reaction equation

HRID 451880 reaction equation
O[C:2]1([CH2:5][CH2:6][C@@H:7]([CH2:23][O:24]S(C2C=CC(C)=CC=2)(=O)=O)[CH2:8][C@H:9]2[CH2:13][O:12][C:11]([CH3:15])([CH3:14])[N:10]2[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:4][CH2:3]1.C[Mg+].[Br-]>C1COCC1>[CH2:4]1[C:2]2([CH2:5][CH2:6][C@H:7]([CH2:8][C@H:9]3[CH2:13][O:12][C:11]([CH3:15])([CH3:14])[N:10]3[C:16]([O:18][C:19]([CH3:22])([CH3:20])[CH3:21])=[O:17])[CH2:23][O:24]2)[CH2:3]1

Participants

4

Reactant 2

HCID 59201637HCID 59201637, compoundHCID 178418689HCID 178418689, compound

Product 1

HCID 59201552HCID 59201552, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The (S)-tert-butyl 4-((R)-4-(1-hydroxycyclopropyl)-2-(tosyloxymethyl)butyl)-2,2-dimethyloxazolidine-3-carboxylate was dissolved in 30 mL of THF and MeMgBr (7.0 mL of a 3.0 M solution, 2.0 equiv) was added and the mixture heated to reflux for 56 hr. After cooling to ambient the mixture was quenched by addition of water and the mixture transferred to a separatory funnel. The layers were separated and the organic layer were washed with brine, dried over Na2SO4, filtered and evaporated. The pyran derivative was purified by flash chromatography on silica (40 g) eluting with 0-29% EtOAc in hexanes. This afforded 1.05 g (91% yield) of (S)-tert-butyl 4-(((R)-4-oxaspiro[2.5]oct-6-yl)methyl)-2,2-dimethyloxazolidine-3-carboxylate. MS ESI +ve m/z 348 (M+Na).

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux for 56 hr
  3. temperatureAfter cooling to ambient the mixture
  4. customwas quenched by addition of water
  5. customthe mixture transferred to a separatory funnel
  6. customThe layers were separated
  7. washthe organic layer were washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe pyran derivative was purified by flash chromatography on silica (40 g)
  12. washeluting with 0-29% EtOAc in hexanes

Sources & evidence

ORD record
ord-44aebcf8fbcc48bea7f5e7236bcd7c9a
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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