m-Chloroperbenzoic acid → dibenzyl(1s,3s)-1-((1S)-1-{[(2s)-2-(3-benzyl-2-oxoimidazolidin-1-yl)-3,3-dimethylbutanoyl]amino}-2-phenylethyl)-3-{[n-(methoxycarbonyl)-3-methyl-l-valyl]amino}-4-(4-pyridin-2-ylphenyl)butyl phosphate

HRID 1174407Notes

Reaction equation

HRID 1174407 reaction equation
[CH2:1]([N:8]1[CH2:12][CH2:11][N:10]([C@@H:13]([C:55]([CH3:58])([CH3:57])[CH3:56])[C:14]([NH:16][C@@H:17]([CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[C@@H:18]([OH:47])[CH2:19][C@@H:20]([NH:34][C:35]([C@@H:37]([NH:42][C:43](=[O:46])[O:44][CH3:45])[C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=3)=[CH:24][CH:23]=2)=[O:15])[C:9]1=[O:59])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)[P:63]([O:72][CH2:73][C:74]1[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=1)[O:64][CH2:65][C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1)C.N1C=NN=N1.ClC1C=CC=C(C(OO)=[O:95])C=1>O1CCCC1.C(OCC)(=O)C.ClCCl>[P:63]([O:47][C@H:18]([C@@H:17]([NH:16][C:14](=[O:15])[C@@H:13]([N:10]1[CH2:11][CH2:12][N:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:9]1=[O:59])[C:55]([CH3:58])([CH3:57])[CH3:56])[CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)[CH2:19][C@@H:20]([NH:34][C:35](=[O:36])[C@H:37]([C:38]([CH3:41])([CH3:40])[CH3:39])[NH:42][C:43]([O:44][CH3:45])=[O:46])[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=2)=[CH:24][CH:23]=1)([O:64][CH2:65][C:66]1[CH:67]=[CH:68][CH:69]=[CH:70][CH:71]=1)([O:72][CH2:73][C:74]1[CH:75]=[CH:76][CH:77]=[CH:78][CH:79]=1)=[O:95]

Participants

8

Reactant 4

HCID 70297m-Chloroperbenzoic acidHCID 5066231Dibenzyl diethylphosphoramiditeHCID 11274374A-792611HCID 178418441HCID 178418441, compound

Product 1

HCID 86726251dibenzyl(1s,3s)-1-((1S)-1-{[(2s)-2-(3-benzyl-2-oxoimidazolidin-1-yl)-3,3-dimethylbutanoyl]amino}-2-phenylethyl)-3-{[n-(methoxycarbonyl)-3-methyl-l-valyl]amino}-4-(4-pyridin-2-ylphenyl)butyl phosphateYield 80%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-45 °C

Procedure

A solution of the compound of Example 111 (0.100 g, 0.124 mmol), dibenzyl diethylphosphoramidite (0.088 mL, 294 mmol), and 1H-tetrazole (0.045 g, 0.642 mmol) in tetrahydrofuran (1.2 mL) was stirred at room temperature for 12 hours. Dichloromethane (1.2 mL) was added and the mixture was cooled to −45° C., followed by addition of m-chloroperbenzoic acid (0.075 g, 0.434 mmol). After stirring for 30 minutes at −45° C., the reaction was diluted with ethyl acetate and washed twice with 10% Na2CO3 and then with brine. The organic phase was dried over MgSO4, filtered and evaporated. The residue was purified by chromatography on silica gel, eluting with a gradient starting with dichloromethane and ending with ethyl acetate, to give the title compound (0.104 g, 80% yield).

Workup

  1. washwashed twice with 10% Na2CO3
  2. dry with materialThe organic phase was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was purified by chromatography on silica gel
  6. washeluting with a gradient

Sources & evidence

ORD record
ord-6c2a67341fd04c1ebab3e3b019585051
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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