Phthalimide → tert-butyl (2S)-2-[5-(4-[(1,3-dioxo-2,3-dihydro-1H-2-isoindolyl)methyl]-phenoxymethyl)-1,2,4-oxadiazol-3-yl]-1-piperidinecarboxylate

HRID 397650Notes

Reaction equation

HRID 397650 reaction equation
[C:1]1(=[O:11])[NH:5][C:4](=[O:6])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.O[CH2:13][C:14]1[CH:39]=[CH:38][C:17]([O:18][CH2:19][C:20]2[O:24][N:23]=[C:22]([C@@H:25]3[CH2:30][CH2:29][CH2:28][CH2:27][N:26]3[C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[N:21]=2)=[CH:16][CH:15]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>O1CCCC1>[O:6]=[C:4]1[C:3]2[C:2](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:1](=[O:11])[N:5]1[CH2:13][C:14]1[CH:15]=[CH:16][C:17]([O:18][CH2:19][C:20]2[O:24][N:23]=[C:22]([C@@H:25]3[CH2:30][CH2:29][CH2:28][CH2:27][N:26]3[C:31]([O:33][C:34]([CH3:35])([CH3:37])[CH3:36])=[O:32])[N:21]=2)=[CH:38][CH:39]=1

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 57274150tert-butyl (2S)-2-(5-[4-(hydroxymethyl)phenoxymethyl]-1,2,4-oxadiazol-3-yl)-1-piperidinecarboxylate

Product 1

HCID 57063716tert-butyl (2S)-2-[5-(4-[(1,3-dioxo-2,3-dihydro-1H-2-isoindolyl)methyl]-phenoxymethyl)-1,2,4-oxadiazol-3-yl]-1-piperidinecarboxylateYield 77.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Phthalimide (480 mg) was added to a solution of tert-butyl (2S)-2-(5-[4-(hydroxymethyl)phenoxymethyl]-1,2,4-oxadiazol-3-yl)-1-piperidinecarboxylate [see Preparation 13] (1.06 g) in tetrahydrofuran (10 ml). The mixture was cooled to 0° C. and triphenylphosphine (1.07 g) was added followed by diethylazodicarboxylate (0.642 ml). The resulting yellow solution was stirred at 0° C. for 10 mins. and then at room temperature for 1 hour. The mixture was evaporated to a low volume under reduced pressure and partitioned between dichloromethane and water. The organic layer was separated, washed with brine, dried over magnesium sulphate and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 90:10 changing to 70:30, by volume, hexane:ethyl acetate to afford tert-butyl (2S)-2-[5-(4-[(1,3-dioxo-2,3-dihydro-1H-2-isoindolyl)methyl]phenoxymethyl)-1,2,4-oxadiazol-3-yl]-1-piperidinecarboxylate (1.09 g) as a white solid.

Workup

  1. waitand then at room temperature for 1 hour
  2. customThe mixture was evaporated to a low volume under reduced pressure
  3. custompartitioned between dichloromethane and water
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over magnesium sulphate
  7. customthe solvent was removed under reduced pressure
  8. customThe crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 90:10 changing to 70:30, by volume, hexane

Sources & evidence

ORD record
ord-8d0f8291be084bedbb19515fe9c31ed5
Source dataset
uspto-grants-2003_08
Patent number
US06610707B1

Reaction notes

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