Lithium Hexamethyldisilazide → (4R,5S)-3-[(R)-3-(3-benzyloxymethyl-2-methoxy-pyridin-4-yl)-3-hydroxy-pentanoyl]-4,5-diphenyl-oxazolidin-2-one

HRID 646614Notes

Reaction equation

HRID 646614 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:11]([N:14]1[C@H:18]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C@H:17]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[O:16][C:15]1=[O:31])(=[O:13])[CH3:12].[CH2:32]([O:39][CH2:40][C:41]1[C:42]([O:51][CH3:52])=[N:43][CH:44]=[CH:45][C:46]=1[C:47](=[O:50])[CH2:48][CH3:49])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>C1COCC1>[CH2:32]([O:39][CH2:40][C:41]1[C:42]([O:51][CH3:52])=[N:43][CH:44]=[CH:45][C:46]=1[C@@:47]([OH:50])([CH2:48][CH3:49])[CH2:12][C:11]([N:14]1[C@H:18]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C@H:17]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[O:16][C:15]1=[O:31])=[O:13])[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 105411281-(3-Benzyloxymethyl-2-methoxy-pyridin-4-yl)-propan-1-oneHCID 16088061(4R,5S)-3-Acetyl-4,5-diphenyloxazolidin-2-one

Product 1

HCID 16088745(4R,5S)-3-[(R)-3-(3-benzyloxymethyl-2-methoxy-pyridin-4-yl)-3-hydroxy-pentanoyl]-4,5-diphenyl-oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A 10 ml round bottomed flask was charged with 389.4 μL lithium bis(trimethylsilyl)amide solution (1.0 M in THF, 0.385 mmol, 1.1 eq) and the solution was cooled to −78° C. 108.4 mg (4R,5S)-3-acetyl-4,5-diphenyl-oxazolidin-2-one (0.385 mmol, 1.1 eq), as obtainable from Example 8, in 650 μL THF were slowly added (addition time: 5 min). During the addition, the color changed from colorless to bright yellow. After 2 h at −78° C., the solution was cooled to −95° C. and 100.0 mg 1-(3-benzyloxymethyl-2-methoxy-pyridin-4-yl)-propan-1-one (0.350 mmol), as obtainable from Example 7, dissolved in 400 μL THF were slowly added (addition time: 5 min). The solution was kept for additional 30 min at −95° C. and then for 45 min at −78° C. Subsequently, the reaction was quenched by addition of 5 mL aqueous 0.5 M HCl. The mixture was extracted three times with 10 mL, in total 30 mL dichloromethane and the combined extracts were dried over 1 g sodium sulfate (30 min) and filtered. The filter cake was washed with 2 mL dichloromethane. After removal of solvent in a rotary evaporator (40° C., 5 mbar), the title compound was obtained as a colorless oil (206.7 mg, 104% by weight, dr=92:8 (1H-NMR).

Workup

  1. addition(addition time: 5 min)
  2. additionDuring the addition
  3. temperaturethe solution was cooled to −95° C.
  4. additionwere slowly added
  5. addition(addition time: 5 min)
  6. waitThe solution was kept for additional 30 min at −95° C.
  7. waitfor 45 min at −78° C
  8. customSubsequently, the reaction was quenched by addition of 5 mL aqueous 0.5 M HCl
  9. extractionThe mixture was extracted three times with 10 mL
  10. dry with materialin total 30 mL dichloromethane and the combined extracts were dried over 1 g sodium sulfate (30 min)
  11. filtrationfiltered
  12. washThe filter cake was washed with 2 mL dichloromethane
  13. customAfter removal of solvent
  14. customin a rotary evaporator (40° C., 5 mbar)

Sources & evidence

ORD record
ord-0b341f3fb50546d29ec4108bb2d3c302
Source dataset
uspto-grants-2010_04
Patent number
US07705155B2

Reaction notes

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