1,3,5-Trioxane → (S)-4-Benzyl-3-((R)-2-hydroxymethyl-4-methylpentanoyl)oxazolidin-2-one

HRID 1472247Notes

Reaction equation

HRID 1472247 reaction equation
[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:20])[CH2:15][CH2:16][CH:17]([CH3:19])[CH3:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[O:30]1COCO[CH2:31]1>C(Cl)Cl.[Ti](Cl)(Cl)(Cl)Cl>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:20])[C@@H:15]([CH2:31][OH:30])[CH2:16][CH:17]([CH3:18])[CH3:19])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 80811,3,5-TrioxaneHCID 81531DiisopropylethylamineHCID 10869526(S)-4-Benzyl-3-(4-methylpentanoyl)oxazolidin-2-one

Product 1

HCID 59556783(S)-4-Benzyl-3-((R)-2-hydroxymethyl-4-methylpentanoyl)oxazolidin-2-oneYield 98.3%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalyst2×HCID 6344DichloromethaneSolvent4×

Conditions

Temperature
0 °C

Procedure

Intermediate (2a) (14.5 g, 46.3 mmol) was dissolved in DCM (151 mL, 2.4 mol) and stirred at 0° C. under nitrogen. 1M titanium tetrachloride in DCM (48.6 mL) was added and stirred for 15 minutes. DIPEA (8.9 mL, 51.0 mmol) was added dropwise at 0° C. and the mixture was stirred for 75 minutes. 1,3,5-Trioxane (4.6 g, 51.0 mmol) in DCM (30 mL) was then added. After 10 minutes a second equivalent of 1M titanium tetrachloride in DCM (48.6 mL) was added and the mixture stirred at 0° C. for 5 hours. The reaction was then quenched with 250 mL of saturated ammonium chloride. Water and DCM were added, and the aqueous phase was extracted twice more with DCM. The organic layers were combined, dried over MgSO4, filtered and concentrated. The resulting material was purified by silica gel chromatography (0-60% EtOAc:hexanes) to provide intermediate (2b) (13.9 g).

Workup

  1. stirringstirred for 15 minutes
  2. stirringthe mixture was stirred for 75 minutes
  3. stirringthe mixture stirred at 0° C. for 5 hours
  4. customThe reaction was then quenched with 250 mL of saturated ammonium chloride
  5. additionWater and DCM were added
  6. extractionthe aqueous phase was extracted twice more with DCM
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting material was purified by silica gel chromatography (0-60% EtOAc:hexanes)

Sources & evidence

ORD record
ord-3548f8e5f1a4493e8cecb7a7cd745965
Source dataset
uspto-grants-2015_04
Patent number
US09012485B2

Reaction notes

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