Triphenylphosphine → (R)-2-[2-(2,5-difluorophenoxy)-1-methylethyl]-1H-isoindole-1,3(2H)-dione

HRID 1633837Notes

Reaction equation

HRID 1633837 reaction equation
[OH:1][CH2:2][C@H:3]([N:5]1[C:13](=[O:14])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]1=[O:15])[CH3:4].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:35][C:36]1[CH:41]=[CH:40][C:39]([F:42])=[CH:38][C:37]=1O.C(OC(N=NC(OCC)=O)=O)C>C1COCC1>[F:35][C:36]1[CH:41]=[CH:40][C:39]([F:42])=[CH:38][C:37]=1[O:1][CH2:2][C@H:3]([N:5]1[C:13](=[O:14])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]1=[O:15])[CH3:4]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 949522,5-DifluorophenolHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 6418462-[(2R)-1-hydroxypropan-2-yl]-2,3-dihydro-1H-isoindole-1,3-dione

Product 1

HCID 69472648(R)-2-[2-(2,5-difluorophenoxy)-1-methylethyl]-1H-isoindole-1,3(2H)-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(R)-2-(2-Hydroxy-1-methylethyl)-1H-isoindole 1,3(2H)-dione (Becker, Y. J. J. Org. Chem. 1980, 45, 2145-51) was diluted with 40 mL THF then treated in order with 7.0 g triphenyl phosphine, 4.0 g of 2,5-difluorophenol and finally with 5.0 mL of diethylazocarboxylate. The reaction became warm to the point of reflux and was allowed to cool to room temperature and stirred at room temperature overnight. The solvent was removed in vacuo and the resulting brown oil was taken up in ethyl acetate (EtOAc). The solution was washed sequentially with aqueous sodium bicarbonate, aqueous ammonium chloride, and brine. Removal of the solvent gave an oil which was chromatographed on silica gel, eluting with 10% ethyl acetate-hexane, to afford 5.4 g of the title compound of Step A as a clear colorless oil: 1H NMR (CDCl3) δ1.57 (d, 3H), 4.22 (dd, 1H), 4.57 (t, 1H), 4.82 (m, 1H), 6.55 (m, 1H), 6.70 (m, 1H), 6.95 (m, 1H), 7.72 (m, 2H), 7.82 (m, 2H).

Workup

  1. temperatureThe reaction became warm to the point
  2. temperatureof reflux
  3. customThe solvent was removed in vacuo
  4. washThe solution was washed sequentially with aqueous sodium bicarbonate, aqueous ammonium chloride, and brine
  5. customRemoval of the solvent
  6. customgave an oil which
  7. customwas chromatographed on silica gel
  8. washeluting with 10% ethyl acetate-hexane

Sources & evidence

ORD record
ord-c5037c209ac44aee918309391411cbe5
Source dataset
uspto-grants-2003_01
Patent number
US06504058B1

Reaction notes

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