Water → HCID 86748020, compound

HRID 1729457Notes

Reaction equation

HRID 1729457 reaction equation
[O:1]=[C:2](N1[C@H](CC2C=CC=CC=2)COC1=O)[C@H:3]([CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])[C@@H:4]([OH:8])[C:5]([CH3:7])=[CH2:6].[OH2:28].C[N+]1([O-])CC[O:33]CC1>C1COCC1.CCCCCC.C(OCC)(=O)C.O=[Os](=O)(=O)=O>[CH2:9]([C@@H:3]1[C@@H:4]([OH:8])[C:5]([CH3:7])([CH2:6][OH:33])[O:1][C:2]1=[O:28])[CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]

Participants

7

Reactant 3

HCID 962WaterHCID 82029Methyl morpholine oxideHCID 18654087HCID 18654087, compound

Product 1

HCID 86748020HCID 86748020, compound

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 8028TetrahydrofuranSolvent2×HCID 21226206Ethyl acetate hexaneSolvent

Procedure

To a 100 ml round bottom flask was introduced 340 mg (0.91 mmol) of 3-(1-oxo-2-(R)-hexyl-3-(R)-hydroxy-4-methyl-4-pentenyl)-4-(R)-(phenylmethyl)-2-oxazolidinone, to which was added 14 ml THF, 0.36 ml water, and 532 mg 4-methylmorpholine N-oxide (4.55 mmol, 5 eq.). The reaction was stirred at room temperature and 0.36 ml of 0.25M OsO4 in THF was added dropwise. After 1 hour, the reaction was quenched with 2 ml of 20% aq. NaHSO3, added to 30 ml of ethyl acetate and extracted twice with 10 ml 20% aq. NaHSO3 then with 10 ml water. The organic layer was separated, dried over MgSO4, and the solvent was removed under vacuum. A 400 MHz proton NMR of the crude reaction product revealed that a mixture of diastereomers at C-4 was formed in about an 8 to 1 ratio, with the stereochemistry of the major product uncertain. The residue was taken up in 60% hexane/ethyl acetate and chromatographed on silica gel using the same solvent mixture. The two diastereomers and the chiral auxilliary proved to be difficult to cleanly separate from each other by chromatography: the minor diastereomer elutes first, followed by the major diastereomer, followed by the chiral auxilliary. Careful chromatography afforded fractions enriched in each product. The total mass of the three products combined was 318 mg (86%).

Workup

  1. customthe reaction was quenched with 2 ml of 20% aq. NaHSO3
  2. additionadded to 30 ml of ethyl acetate
  3. extractionextracted twice with 10 ml 20% aq. NaHSO3
  4. customThe organic layer was separated
  5. dry with materialdried over MgSO4
  6. customthe solvent was removed under vacuum
  7. customA 400 MHz proton NMR of the crude reaction product
  8. additionrevealed that a mixture of diastereomers at C-4
  9. customwas formed in about an 8 to 1 ratio, with the stereochemistry of the major product uncertain
  10. customchromatographed on silica gel using the same solvent mixture
  11. customto cleanly separate from each other by chromatography
  12. customCareful chromatography afforded fractions

Sources & evidence

ORD record
ord-994dde2ede4441dca3919d7a414e58a7
Source dataset
uspto-grants-1994_07
Patent number
US05332807

Reaction notes

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