Triphenylphosphine → HCID 86713875, compound

HRID 521937

Reaction equation

HRID 521937 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[C:4]([F:9])[C:3]=1[C:10]1[S:11][CH:12]=[C:13]([C:15]([O:17]C)=[O:16])[N:14]=1.O[C@@H:20]1[CH2:24][CH2:23][O:22][CH2:21]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[F:9][C:4]1[CH:5]=[C:6]([O:8][C@@H:20]2[CH2:24][CH2:23][O:22][CH2:21]2)[CH:7]=[C:2]([F:1])[C:3]=1[C:10]1[S:11][CH:12]=[C:13]([C:15]([OH:17])=[O:16])[N:14]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 641512(-)-3-HydroxytetrahydrofuranHCID 136377230Methyl 2-(2,6-difluoro-4-hydroxyphenyl)thiazole-4-carboxylate

Product 1

HCID 86713875HCID 86713875, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 2-(2,6-difluoro-4-hydroxy-phenyl)thiazole-4-carboxylate (207 mg, 0.763 mmol) and (R)-3-hydroxytetrahydrofuran (3 equiv., 206 mg) in tetrahydrofuran (5 mL) was added triphenylphosphine (3 equiv., 600 mg) and diisopropyl azodicarboxylate (3 equiv., 0.45 mL) The mixture was stirred at RT for 2 days. The mixture was concentrated and partitioned between EtOAc and water. The organic layer was washed with sat. NaHCO3, brine, dried over Na2SO4 and concentrated. This residue was diluted with THF (3 mL) and water (1 mL) and LiOH (36 mg) was added. After stirring at rt for 2.5 hours, the reaction was neutralized with 1 N HCl(aq), diluted with EtOAc and washed with brine. The organic extracts were dried (Na2SO4) and concentrated in vacuo to provide the title compound, contaminated with triphenylphosphine oxide, and other by-products, which was used without further purification.

Workup

  1. concentrationThe mixture was concentrated
  2. custompartitioned between EtOAc and water
  3. washThe organic layer was washed with sat. NaHCO3, brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. additionThis residue was diluted with THF (3 mL) and water (1 mL) and LiOH (36 mg)
  7. additionwas added
  8. stirringAfter stirring at rt for 2.5 hours
  9. additiondiluted with EtOAc
  10. washwashed with brine
  11. dry with materialThe organic extracts were dried (Na2SO4)
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ebe1ff9fcb5a4c20b9cbe9433f928802
Source dataset
uspto-grants-2016_05
Patent number
US09328106B2

Linked notes

Loading…