Phthalimide → HCID 58592528, compound

HRID 1178848Notes

Reaction equation

HRID 1178848 reaction equation
N(C(OCC)=O)=NC(OCC)=O.C1(=O)NC(=O)C2=CC=CC=C12.FC(F)(F)C1C=C(C=C(C(F)(F)F)C=1)COCC1(C2C=CC=CC=2)CCC(O)C1.[F:53][C:54]([F:91])([F:90])[C:55]1[CH:56]=[C:57]([CH:83]=[C:84]([C:86]([F:89])([F:88])[F:87])[CH:85]=1)[CH2:58][O:59][CH2:60][C:61]1([C:77]2[CH:82]=[CH:81][CH:80]=[CH:79][CH:78]=2)[CH2:65][CH2:64][CH:63]([N:66]2[C:74](=[O:75])[C:73]3[C:68](=[CH:69][CH:70]=[CH:71][CH:72]=3)[C:67]2=[O:76])[CH2:62]1>C1COCC1.C(OCC)(=O)C.O>[F:88][C:86]([F:87])([F:89])[C:84]1[CH:83]=[C:57]([CH:56]=[C:55]([C:54]([F:91])([F:90])[F:53])[CH:85]=1)[CH2:58][O:59][CH2:60][C@:61]1([C:77]2[CH:78]=[CH:79][CH:80]=[CH:81][CH:82]=2)[CH2:65][CH2:64][C@H:63]([N:66]2[C:74](=[O:75])[C:73]3[C:68](=[CH:69][CH:70]=[CH:71][CH:72]=3)[C:67]2=[O:76])[CH2:62]1

Participants

8

Reactant 4

HCID 6809PhthalimideHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 58592523HCID 58592523, compoundHCID 76825706HCID 76825706, compound2×

Product 1

HCID 58592528HCID 58592528, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tripehnylphosphine (102 mg) in THF (0.20 mL) at 0° C. was added diethyl azodicarboxylate (61 μL) and the resulting solution was stirred at 0° C. for 30 min. Phthalimide (57 mg) was added followed by 3-((3,5-bis(trifluoromethyl)benzyloxy)methyl)-3-phenylcyclopentanol (available from Step E of Example 1) (148 mg) in THF (0.50 mL), and the reaction mixture was stirred at 0° C. for 2 h. The reaction mixture was diluted with ethyl acetate and water was added. The aqueous layer was extracted with ethyl acetate, the combined organic layers were dried over anhydrous sodium sulfate and filtered, and the filtrate was evaporated in vacuo. The residue was purified by preparative TLC eluting with 20% ethyl acetate/80% hexanes to give two products as racemates: 2-((1SR,3RS)-3-((3,5-bis(trifluoromethyl)benzyloxy)methyl)-3-phenylcyclopentyl)isoindoline-1,3-dione (less polar fraction) and 2-((1RS,3RS)-3-((3,5-bis(trifluoromethyl)benzyloxy)methyl)-3-phenylcyclopentyl)isoindoline-1,3-dione (more polar fraction).

Workup

  1. stirringthe reaction mixture was stirred at 0° C. for 2 h
  2. additionwas added
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. dry with materialthe combined organic layers were dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customthe filtrate was evaporated in vacuo
  7. customThe residue was purified by preparative TLC
  8. washeluting with 20% ethyl acetate/80% hexanes
  9. customto give two products as racemates

Sources & evidence

ORD record
ord-d699b748ff0a4a06adc91121ab6d28a4
Source dataset
uspto-grants-2007_10
Patent number
US07276631B2

Reaction notes

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