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

HRID 2111540ノート

反応式

HRID 2111540 の反応式
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

参加物

6

反応物 4

HCID 6410tert-Butyl hydroperoxideHCID 8857Ethyl AcetateHCID 86608592HCID 86608592、化合物HCID 178418339Butyllithium

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-e73bf99c47724c258ac5499816384022
出典データセット
uspto-grants-2009_04
特許番号
US07521427B2

反応ノート

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