Phthalimide → (R)-2-(2-methyl-4,4,4-trifluorobutyl)-1H-isoindole-1,3(2H)-dione

HRID 1975431Notes

Reaction equation

HRID 1975431 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[CH3:13][C@H:14]([CH2:17][C:18]([F:21])([F:20])[F:19])[CH2:15]O.[C:22]1(=[O:32])[NH:26][C:25](=[O:27])[C:24]2=[CH:28][CH:29]=[CH:30][CH:31]=[C:23]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(OCC)C.O1CCCC1>[CH3:13][C@H:14]([CH2:17][C:18]([F:21])([F:20])[F:19])[CH2:15][N:26]1[C:22](=[O:32])[C:23]2[C:24](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:25]1=[O:27]

Participants

7

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 10351792(2R)-4,4,4-trifluoro-2-methylbutan-1-ol

Product 1

HCID 10378474(R)-2-(2-methyl-4,4,4-trifluorobutyl)-1H-isoindole-1,3(2H)-dioneYield 75%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

Diethyl azodicarboxylate (15.4 mL) was added to a 0° C., stirred slurry of (R)-2-methyl-4,4,4-trifluorobutan-1-ol (about 12.0 g), phthalimide (13.4 g), and triphenylphosphine (23.7 g) in diethyl ether (about 6.5 g, see above) and dry tetrahydrofuran (110 mL), warmed to room temperature overnight, and stirred an additional 8 h. The mixture was evaporated, methylene chloride was added to the residue, and the slurry was filtered. The filtrate was purified by flash chromatography, eluting with 1:1 methylene chloride:hexanes, to give (R)-2-(2-methyl-4,4,4-trifluorobutyl)-1H-isoindol-1,3(2H)-dione (17.1 g, 75%) as a white solid; mp 45°-47° C.; partial NMR (400 MHz, CDCl3): 1.08 (d, 3H, CH3), 1.94-2.07 (m, 1H, CF3CH2), 2.14-2.31 (m, 1H, CF3CH2), 2.36-2.50 (m, 1H, CHCH3), 3.58 (dd, 1H, CH2N), 3.64 (dd, 1H, CH2N).

Workup

  1. customThe mixture was evaporated
  2. additionmethylene chloride was added to the residue
  3. filtrationthe slurry was filtered
  4. customThe filtrate was purified by flash chromatography
  5. washeluting with 1:1 methylene chloride

Sources & evidence

ORD record
ord-0e04af7a092c4e47835eba2735611f9e
Source dataset
uspto-grants-1994_02
Patent number
US05286740

Reaction notes

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