Phthalimide → (E)-2-(3-(3,5-difluoro-4-phenoxyphenyl)-2-methylallyl)isoindoline-1,3-dione

HRID 45703Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4](/[CH:16]=[C:17](\[CH3:20])/[CH2:18]O)[CH:5]=[C:6]([F:15])[C:7]=1[O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C:40]1(=[O:50])[NH:44][C:43](=[O:45])[C:42]2=[CH:46][CH:47]=[CH:48][CH:49]=[C:41]12.N(C(OCC)=O)=NC(OCC)=O>C1(C)C=CC=CC=1.CCOC(C)=O>[F:1][C:2]1[CH:3]=[C:4](/[CH:16]=[C:17](\[CH3:20])/[CH2:18][N:44]2[C:40](=[O:50])[C:41]3[C:42](=[CH:46][CH:47]=[CH:48][CH:49]=3)[C:43]2=[O:45])[CH:5]=[C:6]([F:15])[C:7]=1[O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of (E)-3-(3,5-difluoro-4-phenoxyphenyl)-2-methylprop-2-en-1-ol (Intermediate 93.1) (410 mg, 1.49 mmol) in dry toluene (7.45 mL) under N2 was added PPh3 and phthalimide. The resulting solution was cooled to 0° C. and diethyl azodicarboxylate (DEAD, 0.748 mL) was added dropwise over several minutes. The reaction was allowed to warm to room temperature and stirred overnight. After diluting with EtOAc (20 mL), the organic layer was washed with water (2×30 mL), brine (30 mL) and dried over Na2SO4. After removal of solvent, the resulting residue was applied to a silica gel column (15% EtOAc in hexanes) to yield 385 mg of the title compound (63%) as an oil.

Workup

temperatureto warm to room temperature
washthe organic layer was washed with water (2×30 mL), brine (30 mL)
dry with materialdried over Na2SO4
customAfter removal of solvent

Sources & evidence

ORD record: ord-640bf40bf53945d390802b49785585d2
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08541448B2

Reaction notes

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