2,6-Lutidine → (4R)-4-benzyl-3-[(2R,3R)-2-styryl-tetrahydro-pyran-3-carbonyl]-oxazolidin-2-one

HRID 497480Notes

Reaction equation

HRID 497480 reaction equation
[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:30])[C@H:15]([CH2:26][CH2:27][CH2:28]O)[C@H:16]([OH:25])[CH:17]=[CH:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C(C)=CC=CC=1C.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O>C(Cl)Cl.C(OCC)(=O)C>[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14]([C@@H:15]1[CH2:26][CH2:27][CH2:28][O:25][C@@H:16]1[CH:17]=[CH:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)=[O:30])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 79372,6-LutidineHCID 67749Trifluoromethanesulfonic anhydrideHCID 69747877(4r)-4-Benzyl-3-[(2r,3r)-3-hydroxy-2-(3-hydroxy-propyl)-5-phenyl-pent-4-enoyl]-oxazolidin-2-one

Product 1

HCID 69750906(4R)-4-benzyl-3-[(2R,3R)-2-styryl-tetrahydro-pyran-3-carbonyl]-oxazolidin-2-oneYield 63.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirring solution of (4R)-4-benzyl-3-[(2R,3R)-3-hydroxy-2-(3-hydroxy-propyl)-5-phenyl-pent-4-enoyl]-oxazolidin-2-one (3.88 g, 9.49 mmol) in anhydrous methylene chloride (100 mL) in a flame-dried round bottom flask under N2 at −78° C. was added 2,6-lutidine (2.76 mL, 23.7 mmol). Trifluoromethanesulfonic anhydride (1.68 mL, 9.96 mmol) was then added dropwise; after 5 min, the reaction was quenched with saturated aqueous sodium bicarbonate (50 mL), the layers were separated, and the aqueous layer was washed with methylene chloride (2×50 mL). The combined organic layers were dried over sodium sulfate, concentrated in vacuo, and purified by flash chromatography (SiO2, 20-30% ethyl acetate in hexanes) to yield a pale yellow oil. The resulting oil was diluted with ethyl acetate (50 mL), the organic layer was washed once with 1N aqueous hydrogen chloride (50 mL) to remove residual 2,6-lutidine, and the ethyl acetate was concentrated in vacuo to yield the desired tetrahydropyran (2.35 g, 63.3%) as a pale yellow oil. MS (APCI), m+/z: (M+H)+=392.4.

Workup

  1. customthe reaction was quenched with saturated aqueous sodium bicarbonate (50 mL)
  2. customthe layers were separated
  3. washthe aqueous layer was washed with methylene chloride (2×50 mL)
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. custompurified by flash chromatography (SiO2, 20-30% ethyl acetate in hexanes)
  7. customto yield a pale yellow oil
  8. washthe organic layer was washed once with 1N aqueous hydrogen chloride (50 mL)
  9. customto remove residual 2,6-lutidine
  10. concentrationthe ethyl acetate was concentrated in vacuo

Sources & evidence

ORD record
ord-ae2e9321e75941a1a05cce1e8505e62b
Source dataset
uspto-grants-2005_09
Patent number
US06949546B2

Reaction notes

Loading…