Phthalimide → (+/-)-Benzyl 3-(1,3-dioxoisoindolin-2-yl)-4-fluoropiperidine-1-carboxylate

HRID 69894Notes

Reaction equation

HRID 69894 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O.[F:32][CH:33]1[CH2:38][CH2:37][N:36]([C:39]([O:41][CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)=[O:40])[CH2:35][CH:34]1O.[C:50]1(=[O:60])[NH:54][C:53](=[O:55])[C:52]2=[CH:56][CH:57]=[CH:58][CH:59]=[C:51]12>C1(C)C=CC=CC=1>[O:55]=[C:53]1[C:52]2[C:51](=[CH:59][CH:58]=[CH:57][CH:56]=2)[C:50](=[O:60])[N:54]1[CH:34]1[CH:33]([F:32])[CH2:38][CH2:37][N:36]([C:39]([O:41][CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)=[O:40])[CH2:35]1

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 42609255Benzyl 4-fluoro-3-hydroxypiperidine-1-carboxylate

Product 1

HCID 86669189(+/-)-Benzyl 3-(1,3-dioxoisoindolin-2-yl)-4-fluoropiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of triphenylphosphine (3.0 equiv.) in toluene (0.25 M solution) was added DEAD (3.0 equiv.) at room temperature, which was stirred for 15 min. Then, (+/−)-benzyl 4-fluoro-3-hydroxypiperidine-1-carboxylate (1.0 equiv.) was added to the reaction mixture. After being stirred for 10 min, phthalimide (3.0 equiv.) was added and the reaction mixture was stirred for 15 h. The reaction mixture was extracted with ethyl acetate, which was washed with water and brine. The organic phase was dried over anhydrous sodium sulfate and filtered. After volatile materials were removed, (+/−)-benzyl 3-(1,3-dioxoisoindolin-2-yl)-4-fluoropiperidine-1-carboxylate was obtained by silica column chromatography (10% to 20% EtOAc in hexanes, 20%). LCMS (m/z): 383.0 (MH+), Rt=1.0 min.

Workup

  1. stirringAfter being stirred for 10 min
  2. stirringthe reaction mixture was stirred for 15 h
  3. extractionThe reaction mixture was extracted with ethyl acetate, which
  4. washwas washed with water and brine
  5. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customAfter volatile materials were removed

Sources & evidence

ORD record
ord-94ad96816b4846179ea1308b26866ee1
Source dataset
uspto-grants-2014_09
Patent number
US08822497B2

Reaction notes

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