Phthalimide → Phenylmethyl 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-piperidinecarboxylate

HRID 1077

Reaction equation

HRID 1077 reaction equation
CCOC(/N=N/C(OCC)=O)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:32]([N:42]1[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]1)([O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:33].[C:48]1(=[O:58])[NH:52][C:51](=[O:53])[C:50]2=[CH:54][CH:55]=[CH:56][CH:57]=[C:49]12>C1COCC1>[CH2:35]([O:34][C:32]([N:42]1[CH2:47][CH2:46][CH:45]([N:52]2[C:51](=[O:53])[C:50]3=[CH:54][CH:55]=[CH:56][CH:57]=[C:49]3[C:48]2=[O:58])[CH2:44][CH2:43]1)=[O:33])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 228749Benzyl piperidine-1-carboxylateHCID 5462977Diethyl azodicarboxylate

Product 1

HCID 21831105Phenylmethyl 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-piperidinecarboxylateYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of DEAD (1.61 mL, 10.2 mmol) in 20 mL of THF was added to a solution of triphenylphosphine (2.69 g, 10.3 mmol), the N-Cbz-piperidine prepared in Example 16A (2.36 g, 100 mmol) and phthalimide (1.50 g, 10.2 mmol) in 80 mL of THF. After stirring 10.5 h at R.T. the mixture was quenched with water, extracted with EtOAc (3×) and the combined extracts washed with brine solution, dried over Na2SO4 and concentrated to give the crude product. Purification of this material by chromatography (hexanes/EtOAc; 2:1) gave 1.81 g, (50%) of 1-benzyloxycarbonyl-4-phthalimidylpiperidine. [1H]-NMR(CDCl3) consistent with structure.

Workup

  1. customwas quenched with water
  2. extractionextracted with EtOAc (3×)
  3. washthe combined extracts washed with brine solution
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customto give the crude product
  7. customPurification of this material by chromatography (hexanes/EtOAc; 2:1)

Sources & evidence

ORD record
ord-d13c6a79a6d1480ca22e3b132fc186d6
Source dataset
uspto-grants-1998_03
Patent number
US05723490

Linked notes

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