Dimethyl Sulfide → (4S,5R)-3-((2R,3R)-2,3-Dimethyl-hexanoyl)-4,5-diphenyl-oxazolidin-2-one

HRID 132659Notes

Reaction equation

HRID 132659 reaction equation
S(C)C.[Li+].[Cl-].[CH3:6][Mg]Cl.[CH3:9]/[C:10](=[CH:31]\[CH2:32][CH2:33][CH3:34])/[C:11]([N:13]1[C@@H:17]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@@H:16]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[O:15][C:14]1=[O:30])=[O:12]>C1COCC1.[NH4+].[OH-].[NH4+].[Cl-].O.C(O)(=O)C>[CH3:9][C@H:10]([C@H:31]([CH3:6])[CH2:32][CH2:33][CH3:34])[C:11]([N:13]1[C@@H:17]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@@H:16]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[O:15][C:14]1=[O:30])=[O:12]

Participants

10

Reactant 4

HCID 1068Dimethyl SulfideHCID 433294Lithium ChlorideHCID 25232302(4S,5R)-3-((E)-2-Methyl-hex-2-enoyl)-4,5-diphenyl-oxazolidin-2-oneHCID 178418332HCID 178418332, compound2×

Product 1

HCID 25232465(4S,5R)-3-((2R,3R)-2,3-Dimethyl-hexanoyl)-4,5-diphenyl-oxazolidin-2-one

Reagents, catalysts & solvents 5

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 14923Ammonium HydroxideSolventHCID 25517Ammonium ChlorideSolvent

Procedure

A 22 L 4-neck round bottom flask was equipped with an addition funnel, mechanical stirrer, and nitrogen inlet. The system was purged with nitrogen for 1 hour. THF (6 L) were charged to the flask followed by 1236 g (6.01 mol) of CuBr.S(CH3)2 and 364 g (8.59 mol) of LiCl. The reaction was stirred for 15 minutes at ambient temperature. The solution was cooled to −35° C. and 3.96 L (11.88 mol) of a 3M solution of CH3MgCl in THF was charged at a rate as to keep the internal temperature of the reaction mixture below −25° C. The reaction was stirred for 1 hour after the addition of CH3MgCl was complete. (4S,5R)-3-((E)-2-Methyl-hex-2-enoyl)-4,5-diphenyl-oxazolidin-2-one (1.00 Kg, 2.86 mol) was added as a solid in one portion and the reaction was stirred at −30° C. for 4 hours. The reaction mixture was transferred over a 2 hour period into another 22 L flask equipped with a mechanical stirrer, transfer line, vacuum line, and containing 4 L of 1:1 acetic acid:THF solution cooled in an ice-water bath. The quenched solution was stirred for 30 minutes and then diluted with 4 L of 2M NH4OH in saturated aqueous NH4Cl and 2 L of water. The biphasic mixture was stirred for 15 minutes and the phases separated. The organic phase was washed 4× with 4 L aliquots of the 2M NH4OH solution. No more blue color was observed in the washes or the organic phase so the organic phase was diluted with 8 L of water and the THF was distilled off until the internal temperature of the distillation pot reached 95° C. The suspension was cooled to ambient temperature and filtered. The solids were washed with 4 L of water and suction dried to give 868.2 g of an off white solid. This material was recrystallized from 2 L of 95:5 heptane:toluene with a cooling rate of 5° C. per hour to provide 317.25 g of the titled compound as a white solid: 1H NMR (CDCl3) 7.12-6.85 (m, 10H), 5.90 (d, 1H, J=8.06 Hz), 5.72 (d, 1H, J=7.81), 3.83-3.76 (m, 1H), 1.95-1.89 (m, 1H), 1.35-1.31 (m, 1H), 1.11 (d, 3H, J=6.84), 1.10-0.95 (m, 3H), 0.92 (d, 3H, J=6.59), 0.76 (t, 3H, J=7.20) MS (APCI) M+1=366.2.

Workup

  1. customA 22 L 4-neck round bottom flask was equipped with an addition funnel, mechanical stirrer, and nitrogen inlet
  2. customThe system was purged with nitrogen for 1 hour
  3. additionTHF (6 L) were charged to the flask
  4. temperatureThe solution was cooled to −35° C.
  5. customthe internal temperature of the reaction mixture below −25° C
  6. stirringThe reaction was stirred for 1 hour
  7. stirringthe reaction was stirred at −30° C. for 4 hours
  8. waitThe reaction mixture was transferred over a 2 hour period into another 22 L flask
  9. customequipped with a mechanical stirrer
  10. stirringThe quenched solution was stirred for 30 minutes
  11. stirringThe biphasic mixture was stirred for 15 minutes
  12. customthe phases separated
  13. washThe organic phase was washed 4× with 4 L aliquots of the 2M NH4OH solution
  14. additionthe organic phase so the organic phase was diluted with 8 L of water
  15. distillationthe THF was distilled off until the internal temperature of the distillation
  16. custompot reached 95° C
  17. temperatureThe suspension was cooled to ambient temperature
  18. filtrationfiltered
  19. washThe solids were washed with 4 L of water and suction
  20. customdried
  21. customto give 868.2 g of an off white solid
  22. customThis material was recrystallized from 2 L of 95:5 heptane

Sources & evidence

ORD record
ord-a8e503d37fa7453daa3fb62e4cf1d504
Source dataset
uspto-grants-2008_06
Patent number
US07388023B2

Reaction notes

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