m-Chloroperbenzoic acid → (1S,3R)-1-((1S)-1-{[(2S)-2-(3-{[6-(1-{[bis(benzyloxy)phosphoryl]oxy}-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 tert-butyl carbonate

HRID 1174411Notes

Reaction equation

HRID 1174411 reaction equation
[C:1](=[O:70])([O:7][C@H:8]([C@@H:37]([NH:45][C:46](=[O:69])[C@@H:47]([N:52]1[CH2:56][CH2:55][N:54]([CH2:57][C:58]2[CH:63]=[CH:62][CH:61]=[C:60]([C:64]([OH:67])([CH3:66])[CH3:65])[N:59]=2)[C:53]1=[O:68])[C:48]([CH3:51])([CH3:50])[CH3:49])[CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[CH2:9][C@H:10]([NH:24][C:25](=[O:36])[C@H:26]([C:32]([CH3:35])([CH3:34])[CH3:33])[NH:27][C:28]([O:30][CH3:31])=[O:29])[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)=[CH:14][CH:13]=1)[O:2][C:3]([CH3:6])([CH3:5])[CH3:4].C(N(CC)[P:74]([O:83][CH2:84][C:85]1[CH:90]=[CH:89][CH:88]=[CH:87][CH:86]=1)[O:75][CH2:76][C:77]1[CH:82]=[CH:81][CH:80]=[CH:79][CH:78]=1)C.N1C=NN=N1.ClC1C=CC=C(C(OO)=[O:106])C=1>O1CCCC1.C(OCC)(=O)C.ClCCl>[C:1](=[O:70])([O:2][C:3]([CH3:4])([CH3:5])[CH3:6])[O:7][C@H:8]([C@@H:37]([NH:45][C:46](=[O:69])[C@@H:47]([N:52]1[CH2:56][CH2:55][N:54]([CH2:57][C:58]2[CH:63]=[CH:62][CH:61]=[C:60]([C:64]([O:67][P:74]([O:75][CH2:76][C:77]3[CH:78]=[CH:79][CH:80]=[CH:81][CH:82]=3)([O:83][CH2:84][C:85]3[CH:86]=[CH:87][CH:88]=[CH:89][CH:90]=3)=[O:106])([CH3:66])[CH3:65])[N:59]=2)[C:53]1=[O:68])[C:48]([CH3:51])([CH3:50])[CH3:49])[CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[CH2:9][C@H:10]([NH:24][C:25](=[O:36])[C@H:26]([C:32]([CH3:35])([CH3:34])[CH3:33])[NH:27][C:28]([O:30][CH3:31])=[O:29])[CH2:11][C:12]1[CH:13]=[CH:14][C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)=[CH:16][CH:17]=1

Participants

8

Reactant 4

HCID 70297m-Chloroperbenzoic acidHCID 5066231Dibenzyl diethylphosphoramiditeHCID 123271177tert-butyl(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 carbonateHCID 178418441HCID 178418441, compound

Product 1

HCID 87387873(1S,3R)-1-((1S)-1-{[(2S)-2-(3-{[6-(1-{[bis(benzyloxy)phosphoryl]oxy}-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 tert-butyl carbonateYield 48.2%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-45 °C

Procedure

A solution of the compound of Example 194A (1.16 mmol), dibenzyl diethylphosphoramidite (1.25 mL, 4.17 mmol), and 1H-tetrazole (0.40 g, 5.71 mmol) in tetrahydrofuran (11.0 mL) was stirred at room temperature for 12 hours. Dichloromethane (11.0 mL) was added and the mixture was cooled to −45° C., followed by addition of m-chloroperbenzoic acid (1.15 g, 6.66 mmol). After stirring for 1 hour 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 75% ethyl acetate in dichloromethane, to give the title compound (0.684 g, 48% yield over two steps).

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-529334a59d8849d0a09e5326d211069c
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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