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

HRID 2111533Notes

Reaction equation

HRID 2111533 reaction equation
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

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-bd206313f881406d9cff5ecf79f01cab
Source dataset
uspto-grants-2009_04
Patent number
US07521427B2

Reaction notes

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