tert-Butyl hydroperoxide → Phenyl-3-(N-carbobenzyloxyleucyl)amino-4-phenylbut-2-enyl Sulfone

HRID 2111533노트

반응식

HRID 2111533 반응식
C([Li])CCC.C(OO)(C)(C)C.[C:12]1([CH:18]([C:79]2[CH:84]=[CH:83][CH:82]=[CH:81][CH:80]=2)[C@H:19]([NH:60][C:61](=[O:78])[C@H:62]([CH2:74][CH:75]([CH3:77])[CH3:76])[NH:63][C:64]([O:66][CH2:67][C:68]2[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=2)=[O:65])[CH:20]=[CH:21][S:22]([CH:25]=[CH:26][C@@H:27]([NH:41][C:42](=[O:59])[C@H:43]([CH2:55][CH:56]([CH3:58])[CH3:57])[NH:44][C:45]([O:47][CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)=[O:46])[CH:28]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)(=[O:24])=[O:23])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.CCOC(C)=O>C1COCC1>[C:29]1([CH:28]([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:27]([NH:41][C:42](=[O:59])[C@H:43]([CH2:55][CH:56]([CH3:57])[CH3:58])[NH:44][C:45]([O:47][CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)=[O:46])=[CH:26][CH2:25][S:22]([CH2:21][CH:20]=[C:19]([NH:60][C:61](=[O:78])[C@H:62]([CH2:74][CH:75]([CH3:77])[CH3:76])[NH:63][C:64]([O:66][CH2:67][C:68]2[CH:69]=[CH:70][CH:71]=[CH:72][CH:73]=2)=[O:65])[CH:18]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:79]2[CH:80]=[CH:81][CH:82]=[CH:83][CH:84]=2)(=[O:23])=[O:24])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

참가 물질

6

반응물 4

HCID 6410tert-Butyl hydroperoxideHCID 8857Ethyl AcetateHCID 86608592HCID 86608592, 화합물HCID 178418339Butyllithium

생성물 1

HCID 86608591Phenyl-3-(N-carbobenzyloxyleucyl)amino-4-phenylbut-2-enyl Sulfone수율 63%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

Butyllithium (3.63 ml, 6.17 mmol, 1.7 M in pentane) was added dropwise to a solution of tert-butylhydroperoxide (2.55 ml, 8.42 mmol, 3.3 M in toluene) in freshly distilled THF (80 ml) at −78° C. under argon. A solution of Cbz-Leu-Phe-VS-Ph (3.00 g, 5.61 mmol) in dry THF (30 ml) was added dropwise. The reaction was continued to stir at −20° C. for 45 minutes (TLC Hex/EtOAc 1:1). The reaction was quenched with saturated aqueous ammonium chloride (50 ml) and allowed to warm to room temperature. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3×30 ml). The extracts were then washed with aqueous sodium sulfite (10%, 3×20 ml). The combined organic layers were dried (MgSO4) and evaporated to give Cbz-Leu-Phe-AS-Ph as a white powder, yield 63%. 1H-NMR (CDCl3) δ 0.8-0.9 (2d, 6H, 2×Leu-CH3), 1.4-1.6 (m, 2H, Leu-CH2), 3.8 (s, 2H, CH2-Phe), 3.9 (d, 2H, CH2—SO2), 4.1 (m, 1H, α-H), 4.8 (t, 1H, CH═), 4.9-5.0 (b, 1H, NH), 5.1 (m, 2H, Cbz), 7.1-7.4 (m, 10H, 2×Ph), 7.5-7.7 (m, 5H, SO2-Ph), 8.4 (b, 1H, NH). 13C NMR (400 MHz, CDCl3) δ 172.1, 156.3, 144.4, 140.8, 135.7, 134.2, 133.6, 131.2, 129.5, 129.4×2, 129.3, 128.8×2, 128.7, 128.6, 128.4, 128.3, 127.8, 127.3, 126.9, 106.3, 67.6, 56.0, 55.6, 41.7, 40.4, 22.1, 21.0, 18.4. MS (FAB+) m/z 535 (M+1, 100%). Anal. Calcd. for C30H34N2O5S: C, 67.39; H, 6.56; N, 5.43. Found: C, 67.41; H, 6.56; N, 5.43.

후처리

  1. customThe reaction was quenched with saturated aqueous ammonium chloride (50 ml)
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with ethyl acetate (3×30 ml)
  4. washThe extracts were then washed with aqueous sodium sulfite (10%, 3×20 ml)
  5. dry with materialThe combined organic layers were dried (MgSO4)
  6. customevaporated

출처 및 근거

ORD 기록
ord-bd206313f881406d9cff5ecf79f01cab
출처 데이터셋
uspto-grants-2009_04
특허 번호
US07521427B2

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