m-Chloroperbenzoic acid → dibenzyl(1s,3s)-1-((1S)-1-{[(2,6-dimethylphenoxy)acetyl]amino}-2-phenylethyl)-3-{[(2s)-3-methyl-2-(2-oxotetrahydropyrimidin-1(2h)-yl)butanoyl]amino}-4-phenylbutyl phosphate

HRID 1968908Notes

Reaction equation

HRID 1968908 reaction equation
[CH2:1]([C@H:8]([NH:33][C:34](=[O:46])[C@@H:35]([N:39]1[CH2:44][CH2:43][CH2:42][NH:41][C:40]1=[O:45])[CH:36]([CH3:38])[CH3:37])[CH2:9][C@H:10]([OH:32])[C@@H:11]([NH:19][C:20](=[O:31])[CH2:21][O:22][C:23]1[C:28]([CH3:29])=[CH:27][CH:26]=[CH:25][C:24]=1[CH3:30])[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)[P:50]([O:59][CH2:60][C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)[O:51][CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)C.N1C=NN=N1.ClC1C=CC=C(C(OO)=[O:82])C=1>C1COCC1.C(OCC)(=O)C.ClCCl>[P:50]([O:32][C@H:10]([C@@H:11]([NH:19][C:20](=[O:31])[CH2:21][O:22][C:23]1[C:24]([CH3:30])=[CH:25][CH:26]=[CH:27][C:28]=1[CH3:29])[CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)[CH2:9][C@@H:8]([NH:33][C:34](=[O:46])[C@@H:35]([N:39]1[CH2:44][CH2:43][CH2:42][NH:41][C:40]1=[O:45])[CH:36]([CH3:38])[CH3:37])[CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)([O:51][CH2:52][C:53]1[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=1)([O:59][CH2:60][C:61]1[CH:62]=[CH:63][CH:64]=[CH:65][CH:66]=1)=[O:82]

Participants

8

Reactant 4

HCID 70297m-Chloroperbenzoic acidHCID 92727LopinavirHCID 5066231Dibenzyl diethylphosphoramiditeHCID 178418441HCID 178418441, compound

Product 1

HCID 42637729dibenzyl(1s,3s)-1-((1S)-1-{[(2,6-dimethylphenoxy)acetyl]amino}-2-phenylethyl)-3-{[(2s)-3-methyl-2-(2-oxotetrahydropyrimidin-1(2h)-yl)butanoyl]amino}-4-phenylbutyl phosphateYield 90%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-45 °C

Procedure

A solution of the compound of Example 3 (0.250 g, 0.40 mmol), dibenzyl diethylphosphoramidite (0.28 mL), and 1H-tetrazole (0.14 g) in THF (4.0 mL) was stirred at room temperature for 68 hours. Dichloromethane (4.0 mL) was added and the mixture was cooled to −45° C., followed by addition of m-chloroperbenzoic acid (0.089 g). 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 chromatography on silica gel, eluting with a gradient starting with 33% ethyl acetate in chloroform and ending with 5% methanol in ethyl acetate, to give the title compound (0.324 g, 90% yield).

Workup

  1. washwashed twice with 10% Na2CO3
  2. dry with materialThe organic phase was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. washeluting with a gradient

Sources & evidence

ORD record
ord-d6a123e67c4740c7b5b4d198ffe29091
Source dataset
uspto-grants-2013_04
Patent number
US08426388B2

Reaction notes

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