Triphenylphosphine → (R)-2-((2-methoxy-4-nitrophenoxy)methyl)oxirane

HRID 1916361Notes

Reaction equation

HRID 1916361 reaction equation
[CH:1]1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[N+:20]([C:23]1[CH:24]=[C:25]([OH:31])[C:26]([O:29][CH3:30])=[CH:27][CH:28]=1)([O-:22])=[O:21].[CH2:32]1[O:34][C@H:33]1CO>C1COCC1>[CH3:1][O:31][C:25]1[CH:24]=[C:23]([N+:20]([O-:22])=[O:21])[CH:28]=[CH:27][C:26]=1[O:29][CH2:30][C@H:33]1[CH2:32][O:34]1

Participants

5

Reactant 3

HCID 11776TriphenylphosphineHCID 694712-Methoxy-5-nitrophenolHCID 6973630(-)-Glycidol

Product 1

HCID 59168988(R)-2-((2-methoxy-4-nitrophenoxy)methyl)oxiraneYield 72%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of Ph3P (23.3 g; 88.7 mmol) in 450 mL of THF cooled to 0° C. was added a solution of di-t-butylazodicarboxylate (20.4 g; 88.7 mmol) in 50 ml of THF over 15 min. After stirring at 0° C. for 10 min 4-nitroguaiacol (10.0 g; 59.1 mmol) was added followed by (S)-glycidol (6.3 mL; 94.6 mmol) over 10 min and the mixture allowed to warm to rt and stir for 2 h. The solution was concentrated and the residue dissolved in EtOAc, washed with H2O and brine, dried over anhydrous MgSO4, filtered and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, Hexanes/EtOAc; 100:0 to 1:3 gradient). Impure fractions were concentrated under reduced pressure and the residue further purified by flash chromatography (silica gel, Hexanes/EtOAc; 100:0 to 0:100 gradient). Pure fractions from both purifications were combined and concentrated under reduced pressure to afford 9.58 g (72%) of the title compound as a yellow solid. 1H NMR (CDCl3) δ 2.78-2.80 (m, 1H), 2.94-2.96 (m, 1H), 3.40-3.43 (m, 1H), 3.96 (s, 3H), 4.06-4.11 (m, 1H), 4.41-4.44 (m, 1H), 6.98 (d, J=8.79 Hz, 1H), 7.75 (d, J=2.20 Hz, 1H), 7.89 (dd, J=8.79 Hz, 2.19 Hz, 1H); 13C NMR (CDCl3) δ 28.20, 44.57, 49.75, 56.28, 70.17, 106.80, 111.71, 117.50, 141.92, 149.20, 153.38; HPLC (Method #1) 2.09 min retention time; LCMS (ES): m/z 226 [M+H]+.

Workup

  1. additionwas added
  2. concentrationThe solution was concentrated
  3. dissolutionthe residue dissolved in EtOAc
  4. washwashed with H2O and brine
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated under reduced pressure
  8. customThe residue was purified by flash chromatography (silica gel, Hexanes/EtOAc; 100:0 to 1:3 gradient)
  9. concentrationImpure fractions were concentrated under reduced pressure
  10. customthe residue further purified by flash chromatography (silica gel, Hexanes/EtOAc; 100:0 to 0:100 gradient)
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-44b730356cf148b5b5e79e770ef34350
Source dataset
uspto-grants-2013_12
Patent number
US08618115B2

Reaction notes

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