Hydrogen Peroxide → HCID 86713196, compound

HRID 1500308Notes

Reaction equation

HRID 1500308 reaction equation
FC(F)(F)C(O)=[O:4].[F:8][CH:9]([F:35])[C:10]([NH:12][C@H:13]([CH2:33][F:34])[C@H:14]([OH:32])[C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:22]=[N:23][C:24]([C:27]3([OH:31])[CH2:30][O:29][CH2:28]3)=[CH:25][CH:26]=2)=[CH:17][CH:16]=1)=[O:11].N1C=CC=CC=1.[CH2:42]([O:49][P:50]([O:58][CH2:59][C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1)N(C(C)C)C(C)C)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.OO.O>O1CCCC1.C(OCC)(=O)C>[P:50]([O:32][C@H:14]([C:15]1[CH:16]=[CH:17][C:18]([C:21]2[CH:22]=[N:23][C:24]([C:27]3([OH:31])[CH2:30][O:29][CH2:28]3)=[CH:25][CH:26]=2)=[CH:19][CH:20]=1)[C@H:13]([NH:12][C:10](=[O:11])[CH:9]([F:8])[F:35])[CH2:33][F:34])([O:49][CH2:42][C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1)([O:58][CH2:59][C:60]1[CH:61]=[CH:62][CH:63]=[CH:64][CH:65]=1)=[O:4]

Participants

9

Reactant 6

HCID 784Hydrogen PeroxideHCID 962WaterHCID 1049PyridineHCID 6422Trifluoroacetic acidHCID 196621Bis(benzyloxy)(diisopropylamino)phosphineHCID 73603447HCID 73603447, compound

Product 1

HCID 86713196HCID 86713196, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Trifluoroacetic acid (118 μL, 1.53 mmol) is added to a stirred solution of the product of step 6, Example 8 (303 mg, 0.764 mmol) and pyridine (124 μL, 1.53 mmol) in tetrahydrofuran (4.78 mL) at 0° C. and after 5 min of stirring bis(benzyloxy)(diisopropylamino)phosphine (0.499 mL, 1.34 mmol) is added dropwise before the reaction mixture is warmed to room temperature. After 7 hours the reaction mixture is cooled at 0° C. and 30% Hydrogen peroxide in water (137 μL, 1.34 mmol) is added dropwise. The mixture is warmed to rt and stirred for 30 min before being diluted with ethyl acetate and quenched with sat. sodium bisulfite solution. The layers were separated and the organic phase washed with brine, dried, and concentrated. The residue is purified by CombiFlash (2×, 12 g column) eluting with 0-100% ethyl acetate in hexanes to arrive at the title compound (310 mg): MS (ESI+) m/z 657.4 [M+H].

Workup

  1. additionis added dropwise before the reaction mixture
  2. temperatureAfter 7 hours the reaction mixture is cooled at 0° C.
  3. temperatureThe mixture is warmed to rt
  4. customquenched with sat. sodium bisulfite solution
  5. customThe layers were separated
  6. washthe organic phase washed with brine
  7. customdried
  8. concentrationconcentrated
  9. customThe residue is purified by CombiFlash (2×, 12 g column)
  10. washeluting with 0-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-5993c955b3424972a99ca396f8f721b2
Source dataset
uspto-grants-2015_12
Patent number
US09206126B2

Reaction notes

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