tert-Butyl hydroperoxide → HCID 178460579, compound

HRID 1766903Notes

Reaction equation

HRID 1766903 reaction equation
[OH:1][CH2:2][C:3]1[CH:48]=[CH:47][CH:46]=[CH:45][C:4]=1[C:5]([O:7][C@:8]([C:37]1[CH:42]=[CH:41][C:40]([F:43])=[CH:39][C:38]=1[F:44])([CH2:31][N:32]1[CH:36]=[N:35][CH:34]=[N:33]1)[C@H:9]([S:11][C@@H:12]1[CH2:17][O:16][C@@H:15](/[CH:18]=[CH:19]/[CH:20]=[CH:21]/[C:22]2[CH:27]=[CH:26][C:25]([C:28]#[N:29])=[CH:24][C:23]=2[F:30])[O:14][CH2:13]1)[CH3:10])=[O:6].N1C=NN=N1.[CH2:54]([O:57][P:58]([O:66][CH2:67][CH:68]=[CH2:69])N(C(C)C)C(C)C)[CH:55]=[CH2:56].C([OH:73])C=C.C(OO)(C)(C)C.C(=O)([O-])O.[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>ClCCl.C(#N)C.CCCCCC.C(OCC)(=O)C>[CH2:67]([O:66][P:58]([O:1][CH2:2][C:3]1[CH:48]=[CH:47][CH:46]=[CH:45][C:4]=1[C:5]([O:7][C@:8]([C:37]1[CH:42]=[CH:41][C:40]([F:43])=[CH:39][C:38]=1[F:44])([CH2:31][N:32]1[CH:36]=[N:35][CH:34]=[N:33]1)[C@H:9]([S:11][C@@H:12]1[CH2:17][O:16][C@@H:15](/[CH:18]=[CH:19]/[CH:20]=[CH:21]/[C:22]2[CH:27]=[CH:26][C:25]([C:28]#[N:29])=[CH:24][C:23]=2[F:30])[O:14][CH2:13]1)[CH3:10])=[O:6])([O:57][CH2:54][CH:55]=[CH2:56])=[O:73])[CH:68]=[CH2:69]

Participants

11

Reactant 7

HCID 6410tert-Butyl hydroperoxideHCID 7858Allyl AlcoholHCID 24477Sodium ThiosulfateHCID 516892Sodium BicarbonateHCID 4686855Diallyl diisopropylphosphoramiditeHCID 178418441HCID 178418441, compoundHCID 178462418HCID 178462418, compound

Product 1

HCID 178460579HCID 178460579, compoundYield 54%

Reagents, catalysts & solvents 3

HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolventHCID 21877088Acetonitrile methylene chlorideSolvent

Conditions

Temperature
0 °C

Procedure

(1R,2R)-2-[[trans-2-[(1E,3E)-4-(4-Cyano-2-fluorophenyl)-1,3-butadienyl]-1,3-dioxan-5-yl]thio]-1-(2,4-difluorophenyl)-1-[(1H-1,2,4-triazol-1-yl)methyl]propyl 2-(hydroxymethyl)benzoate (540 mg, 7.89×10−4 mol) obtained from Example 17-(4) was dissolved in a mixed solvent (3 ml) of dichloromethane-acetonitrile (1:1). Tetrazole (112 mg, 1.6 mmol) and bis(allyloxy)(diisopropylamino)phosphine (Tetrahedron Lett., 30, 4219 (1989); 250 mg, 1.0×10−3 mol) were added thereto at 0° C., and the mixture was stirred at the same temperature for 5 minutes. The mixture was warmed to room temperature, then stirred for 30 minutes, and allyl alcohol (0.1 ml) was added thereto. The mixture was stirred for another 5 minutes, then tert-butyl hydroperoxide (ca. 5M nonane solution, 1.5 ml, ca. 7.5 mmol) was added thereto at 0° C., and the resulting mixture was stirred at room temperature for 30 minutes. A saturated aqueous solution of sodium hydrogen carbonate and an aqueous solution of sodium thiosulfate were added thereto, then the mixture was stirred for 10 minutes and partitioned between ethyl acetate and water. The organic layer was washed successively with a saturated aqueous solution of sodium hydrogen carbonate, a saturated aqueous solution of ammonium chloride, and an aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to give an oily residue. The residue was subjected to chromatography on a silica gel (15 g) column (eluent; ethyl acetate:hexane=2:1˜1:0), and further purified by recycle preparative HPLC [LC-908; Japan Analytical Industry Co., Ltd.; GPC column JAIGEL-1H (20 mm i.d.×600 mm) and JAIGEL-2H (20 mm i.d.×600 mm) connected in series for use; solvent, chloroform] to afford the title compound (363 mg, 54% yield) as a colorless amorphous solid.

Workup

  1. temperatureThe mixture was warmed to room temperature
  2. stirringstirred for 30 minutes
  3. stirringThe mixture was stirred for another 5 minutes
  4. stirringat 0° C., and the resulting mixture was stirred at room temperature for 30 minutes
  5. stirringthe mixture was stirred for 10 minutes
  6. custompartitioned between ethyl acetate and water
  7. washThe organic layer was washed successively with a saturated aqueous solution of sodium hydrogen carbonate
  8. dry with materiala saturated aqueous solution of ammonium chloride, and an aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate
  9. distillationthe solvent was distilled off under reduced pressure
  10. customto give an oily residue
  11. customfurther purified by recycle preparative HPLC [LC-908; Japan Analytical Industry Co., Ltd.; GPC column JAIGEL-1H (20 mm i.d.×600 mm) and JAIGEL-2H (20 mm i.d.×600 mm) connected in series for use; solvent, chloroform]

Sources & evidence

ORD record
ord-37dfde47ec494a8fb7d19044338c2999
Source dataset
uspto-grants-2007_06
Patent number
US07230023B2

Reaction notes

Loading…