(2-Oxopropyl)amine → N-acetonyl-8-benzyl-3-(4-isopropoxy-3-methyl-benzoyl)-11-oxa-3,8-diazaspiro[5.5]undecane-10-carboxamide

HRID 713105

반응식

HRID 713105 반응식
[CH2:1]([N:8]1[CH2:31][CH:30]([C:32]([OH:34])=O)[O:29][C:10]2([CH2:15][CH2:14][N:13]([C:16](=[O:28])[C:17]3[CH:22]=[CH:21][C:20]([O:23][CH:24]([CH3:26])[CH3:25])=[C:19]([CH3:27])[CH:18]=3)[CH2:12][CH2:11]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:35][CH2:36][C:37](=[O:39])[CH3:38].C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CC1CCCO1>>[CH2:36]([NH:35][C:32]([CH:30]1[O:29][C:10]2([CH2:11][CH2:12][N:13]([C:16](=[O:28])[C:17]3[CH:22]=[CH:21][C:20]([O:23][CH:24]([CH3:25])[CH3:26])=[C:19]([CH3:27])[CH:18]=3)[CH2:14][CH2:15]2)[CH2:9][N:8]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:31]1)=[O:34])[C:37]([CH3:38])=[O:39]

참가 물질

5

반응물 4

HCID 215(2-Oxopropyl)amineHCID 73012-MethyltetrahydrofuranHCID 111923Propylphosphonic anhydrideHCID 708728658-Benzyl-3-(4-isopropoxy-3-methyl-benzoyl)-11-oxa-3,8-diazaspiro[5.5]undecane-10-carboxylic acid

생성물 1

HCID 70872809N-acetonyl-8-benzyl-3-(4-isopropoxy-3-methyl-benzoyl)-11-oxa-3,8-diazaspiro[5.5]undecane-10-carboxamide수율 41%

반응 조건

온도
75 °C

실험 절차

To 8-benzyl-3-(4-isopropoxy-3-methyl-benzoyl)-11-oxa-3,8-diazaspiro[5.5]undecane-10-carboxylic acid (201 mg, 0.43 mmol), 1-aminopropan-2-one (47 mg, 0.43 mmol) and T3P (641 μL of 50% w/w, 1.08 mmol) was added 2-methyltetrahydrofuran (1 mL) and the reaction mixture was then 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 20-70% EtOAC in DCM as eluent to afford N-acetonyl-8-benzyl-3-(4-isopropoxy-3-methyl-benzoyl)-11-oxa-3,8-diazaspiro[5.5]undecane-10-carboxamide (92 mg, 41%) as a yellow solid. ESI-MS m/z calc. 521.6. found 522.5 (M+1)+; Retention time: 1.48 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-d4cf9a1e880c4ccd83c7b2365b4112e1
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09181273B2

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