Triethylamine → [8-Benzyl-10-(3-methyl-1,2,4-oxadiazol-5-yl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone

HRID 73038

반응식

HRID 73038 반응식
C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[CH2:19]([N:26]1[CH2:49][CH:48]([C:50]([OH:52])=O)[O:47][C:28]2([CH2:33][CH2:32][N:31]([C:34](=[O:46])[C:35]3[CH:40]=[CH:39][C:38]([O:41][CH:42]([CH3:44])[CH3:43])=[C:37]([CH3:45])[CH:36]=3)[CH2:30][CH2:29]2)[CH2:27]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.O[N:54]=[C:55]([NH2:57])[CH3:56].C(N(CC)CC)C>CC1CCCO1>[CH2:19]([N:26]1[CH2:49][CH:48]([C:50]2[O:52][N:57]=[C:55]([CH3:56])[N:54]=2)[O:47][C:28]2([CH2:33][CH2:32][N:31]([C:34]([C:35]3[CH:40]=[CH:39][C:38]([O:41][CH:42]([CH3:43])[CH3:44])=[C:37]([CH3:45])[CH:36]=3)=[O:46])[CH2:30][CH2:29]2)[CH2:27]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 30926N-HydroxyacetamidineHCID 111923Propylphosphonic anhydrideHCID 708728658-Benzyl-3-(4-isopropoxy-3-methyl-benzoyl)-11-oxa-3,8-diazaspiro[5.5]undecane-10-carboxylic acid

생성물 1

HCID 66548173[8-Benzyl-10-(3-methyl-1,2,4-oxadiazol-5-yl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone수율 39.1%

시약·촉매·용매 1

HCID 73012-Methyltetrahydrofuran용매

반응 조건

온도
75 °C

실험 절차

T3P (546 mg, 510 μL of 50% w/w, 0.86 mmol) was added to a solution of 8-benzyl-3-(4-isopropoxy-3-methyl-benzoyl)-11-oxa-3,8-diazaspiro[5.5]undecane-10-carboxylic acid (160 mg, 0.34 mmol), N′-hydroxyacetamidine (25 mg, 0.34 mmol) and triethylamine (173 mg, 239 μL, 1.71 mmol) in 2-methyltetrahydrofuran (800 μL) and the reaction mixture was heated at 75° C. for 2 hours. The reaction mixture was cooled to room temperature and partitioned between EtOAc/saturated aq. NaHCO3. The layers were separated and the aqueous layer was extracted with EtOAc (2×). The combined organics were dried over Na2SO4, filtered and concentrated in vacuo to a dark foam. The crude product was purified by silica gel column chromatography using 0-30% EtOAc in DCM as eluent to afford [8-benzyl-10-(3-methyl-1,2,4-oxadiazol-5-yl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (67 mg, 39%) as a white solid. ESI-MS m/z calc. 504.6. Found 505.3 (M+1)+; Retention time: 1.63 minutes (3 min run).

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. custompartitioned between EtOAc/saturated aq. NaHCO3
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×)
  5. dry with materialThe combined organics were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo to a dark foam
  8. customThe crude product was purified by silica gel column chromatography

출처 및 근거

ORD 기록
ord-89be0a1a6c684956b8910b66a4ab75ba
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08828996B2

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