m-Chloroperbenzoic acid → dibenzyl(1s,3r)-1-((1S)-1-{[(2s)-2-(3-{[6-(1-hydroxy-1-methylethyl)pyridin-2-yl]methyl}-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 1174408Notes

Reaction equation

HRID 1174408 reaction equation
[OH:1][C@H:2]([C@@H:31]([NH:39][C:40](=[O:63])[C@@H:41]([N:46]1[CH2:50][CH2:49][N:48]([CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[C:54]([C:58]([OH:61])([CH3:60])[CH3:59])[N:53]=2)[C:47]1=[O:62])[C:42]([CH3:45])([CH3:44])[CH3:43])[CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH2:3][C@H:4]([NH:18][C:19]([C@@H:21]([NH:26][C:27](=[O:30])[O:28][CH3:29])[C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)=[CH:8][CH:7]=1.C(N(CC)[P:67]([O:76][CH2:77][C:78]1[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=1)[O:68][CH2:69][C:70]1[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=1)C.N1C=NN=N1.ClC1C=CC=C(C(OO)=[O:99])C=1>O1CCCC1.C(OCC)(=O)C.ClCCl>[P:67]([O:1][C@H:2]([C@@H:31]([NH:39][C:40](=[O:63])[C@@H:41]([N:46]1[CH2:50][CH2:49][N:48]([CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[C:54]([C:58]([OH:61])([CH3:60])[CH3:59])[N:53]=2)[C:47]1=[O:62])[C:42]([CH3:43])([CH3:44])[CH3:45])[CH2:32][C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)[CH2:3][C@H:4]([NH:18][C:19](=[O:20])[C@H:21]([C:22]([CH3:25])([CH3:24])[CH3:23])[NH:26][C:27]([O:28][CH3:29])=[O:30])[CH2:5][C:6]1[CH:7]=[CH:8][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)=[CH:10][CH:11]=1)([O:68][CH2:69][C:70]1[CH:71]=[CH:72][CH:73]=[CH:74][CH:75]=1)([O:76][CH2:77][C:78]1[CH:79]=[CH:80][CH:81]=[CH:82][CH:83]=1)=[O:99]

Participants

8

Reactant 4

HCID 70297m-Chloroperbenzoic acidHCID 5066231Dibenzyl diethylphosphoramiditeHCID 11228293methyl N-[(1S)-1-[[(1R,3S,4S)-3-hydroxy-4-[[(2S)-2-[3-[[6-(1-hydroxy-1-methyl-ethyl)-2-pyridyl]methyl]-2-oxo-imidazolidin-1-yl]-3,3-dimethyl-butanoyl]amino]-5-phenyl-1-[[4-(2-pyridyl)phenyl]methyl]pentyl]carbamoyl]-2,2-dimethyl-propyl]carbamateHCID 178418441HCID 178418441, compound

Product 1

HCID 86726253dibenzyl(1s,3r)-1-((1S)-1-{[(2s)-2-(3-{[6-(1-hydroxy-1-methylethyl)pyridin-2-yl]methyl}-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 50 (0.100 g, 0.116 mmol), dibenzyl diethylphosphoramidite (0.080 mL, 267 mmol), and 1H-tetrazole (0.040 g, 0.571 mmol) in tetrahydrofuran (1.0 mL) was stirred at room temperature for 12 hours. Dichloromethane (1.0 mL) was added and the mixture was cooled to −45° C., followed by addition of m-chloroperbenzoic acid (0.072 g, 0.417 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-77074dc67f5046d697b9bbedecb5691c
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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