Triphenylphosphine → (S)-3-(4-bromo-2-fluoro-5-methylphenoxy)dihydrofuran-2(3H)-one

HRID 407982Notes

Reaction equation

HRID 407982 reaction equation
[OH:1][C@@H:2]1[CH2:6][CH2:5][O:4][C:3]1=[O:7].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:27][C:28]1[C:33]([CH3:34])=[CH:32][C:31](O)=[C:30]([F:36])[CH:29]=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>C1(C)C=CC=CC=1>[Br:27][C:28]1[C:33]([CH3:34])=[CH:32][C:31]([O:1][C@H:2]2[CH2:6][CH2:5][O:4][C:3]2=[O:7])=[C:30]([F:36])[CH:29]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 71570702-Hydroxy-gamma-butyrolactone, (2R)-HCID 108997434-Bromo-2-fluoro-5-methylphenol

Product 1

HCID 67469850(S)-3-(4-bromo-2-fluoro-5-methylphenoxy)dihydrofuran-2(3H)-oneYield 51%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
0 °C

Procedure

(R)-3-hydroxydihydrofuran-2(3H)-one (2.0 g, 20 mmol) was suspended in Toluene (150 mL) and triphenylphosphine (6.2 g, 24 mmol) and 4-bromo-2-fluoro-5-methylphenol (4.8 g, 24 mmol) were added and cooled to 0° C. The solution was degassed with nitrogen bubble for 10 minutes. Di-tert-butyl diazene-1,2-dicarboxylate (5.4 g, 24 mmol) was dissolved in toluene (40 mL) and added to the reaction over 5 minutes. The reaction was allowed to slowly warm to ambient temperature overnight. The toluene was removed and the oily residue was purified over silica gel (20 to 40% EtOAc in hexanes) to afford (S)-3-(4-bromo-2-fluoro-5-methylphenoxy)dihydrofuran-2(3H)-one (2.9 g, 10 mmol, 51% yield).

Workup

  1. customThe solution was degassed with nitrogen
  2. custombubble for 10 minutes
  3. additionadded to the reaction over 5 minutes
  4. temperatureto slowly warm to ambient temperature overnight
  5. customThe toluene was removed
  6. customthe oily residue was purified over silica gel (20 to 40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-c624c1c8618f471d8969019eb9540783
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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