Tributylphosphine → HCID 86605936, compound

HRID 2222043Notes

Reaction equation

HRID 2222043 reaction equation
[OH:1][CH2:2][C:3]1[O:7][N:6]=[C:5]([O:8][CH2:9][C:10]2[N:11]=[C:12]([C:16]3[CH:21]=[CH:20][C:19]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:18][CH:17]=3)[O:13][C:14]=2[CH3:15])[CH:4]=1.[CH2:28]([C:30]1[S:31][CH:32]=[C:33](/[CH:35]=[CH:36]/[C:37]2[C:38](O)=[N:39][N:40]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[CH:41]=2)[N:34]=1)[CH3:29].N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC>O1CCCC1>[CH2:28]([C:30]1[S:31][CH:32]=[C:33](/[CH:35]=[CH:36]/[C:37]2[C:38]([O:1][CH2:2][C:3]3[O:7][N:6]=[C:5]([O:8][CH2:9][C:10]4[N:11]=[C:12]([C:16]5[CH:21]=[CH:20][C:19]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:18][CH:17]=5)[O:13][C:14]=4[CH3:15])[CH:4]=3)=[N:39][N:40]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[CH:41]=2)[N:34]=1)[CH3:29]

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 86605754HCID 86605754, compoundHCID 178437612HCID 178437612, compound

Product 1

HCID 86605936HCID 86605936, compoundYield 30.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of ethyl {4-[4-({[5-(hydroxymethyl)isoxazol-3-yl]oxy}methyl)-5-methyl-1,3-oxazol-2-yl]phenyl}acetate (500 mg), 4-[(E)-2-(2-ethyl-1,3-thiazol-4-yl)ethenyl]-1-phenyl-1H-pyrazol-3-ol (389 mg), 1,1′-(azodicarbonyl)dipiperidine (440 mg), tributylphosphine (0.501 mL) and tetrahydrofuran (20 mL) was stirred at 50° C. for 1 hr. After cooling, the resulting precipitate was removed by filtration, and the filtrate was concentrated. The residue was subjected to silica gel column chromatography and eluted with acetone-hexane (1:5-1:4-1:3, v/v). The obtained eluate was subjected to reversed phase HPLC and eluted with acetonitrile-water (10:90-100:0, v/v). The obtained fraction was concentrated, and saturated aqueous sodium hydrogen carbonate was added to the residue. The mixture was extracted with ethyl acetate-tetrahydrofuran. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated to give ethyl (4-{4-[({5-[({4-[(E)-2-(2-ethyl-1,3-thiazol-4-yl)ethenyl]-1-phenyl-1H-pyrazol-3-yl}oxy)methyl]isoxazol-3-yl}oxy)methyl]-5-methyl-1,3-oxazol-2-yl}phenyl)acetate (257 mg, yield 30%) as pale-yellow amorphous form.

Workup

  1. temperatureAfter cooling
  2. customthe resulting precipitate was removed by filtration
  3. concentrationthe filtrate was concentrated
  4. washeluted with acetone-hexane (1:5-1:4-1:3
  5. washeluted with acetonitrile-water (10:90-100:0
  6. concentrationThe obtained fraction was concentrated
  7. additionsaturated aqueous sodium hydrogen carbonate was added to the residue
  8. extractionThe mixture was extracted with ethyl acetate-tetrahydrofuran
  9. washThe organic layer was washed with saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-c778ecccc00b4cc1ae7b8c640f84d266
Source dataset
uspto-grants-2008_05
Patent number
US07368578B2

Reaction notes

Loading…