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 397650노트

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HRID 397650 반응식
[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

참가 물질

6

반응물 4

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

생성물 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-piperidinecarboxylate수율 77.2%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-8d0f8291be084bedbb19515fe9c31ed5
출처 데이터셋
uspto-grants-2003_08
특허 번호
US06610707B1

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