Tributylphosphine → (6-((1-Methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)methoxy)-4-(trifluoromethyl)-1-benzothiophen-3-yl)acetic acid

HRID 591440Notes

Reaction equation

HRID 591440 reaction equation
C[O:2][C:3](=[O:19])[CH2:4][C:5]1[C:9]2[C:10]([C:15]([F:18])([F:17])[F:16])=[CH:11][C:12]([OH:14])=[CH:13][C:8]=2[S:7][CH:6]=1.[CH3:20][N:21]1[C:25]([CH2:26]O)=[CH:24][C:23]([C:28]([F:31])([F:30])[F:29])=[N:22]1.C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1.C(P(CCCC)CCCC)CCC>C1COCC1>[CH3:20][N:21]1[C:25]([CH2:26][O:14][C:12]2[CH:11]=[C:10]([C:15]([F:18])([F:17])[F:16])[C:9]3[C:5]([CH2:4][C:3]([OH:2])=[O:19])=[CH:6][S:7][C:8]=3[CH:13]=2)=[CH:24][C:23]([C:28]([F:29])([F:31])[F:30])=[N:22]1

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 58456726(1-Methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanolHCID 89767967Methyl 2-[6-hydroxy-4-(trifluoromethyl)benzo[b]thiophen-3-yl]acetate

Product 1

HCID 89768892(6-((1-Methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)methoxy)-4-(trifluoromethyl)-1-benzothiophen-3-yl)acetic acidYield 70.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of methyl(6-hydroxy-4-(trifluoromethyl)-1-benzothiophen-3-yl)acetate (60 mg) and THF (dry) (3 mL) were added (1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanol (37.2 mg), ADDP (62.6 mg) and tri-n-butylphosphine (0.071 mL) at room temperature. The mixture was stirred at room temperature for 12 h. The insoluble material was removed by filtration, and the filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/hexane). To the mixture of the crude material and THF (1 mL) was added 1N NaOH (1 mL) at room temperature for 12 h. The mixture was neutralized with 1N HCl at 0° C. and extracted with EtOAc. The organic layer was separated, washed successively with water and brine, dried over MgSO4 and concentrated in vacuo. The solid was crystallized from EtOAc-hexane to give the title compound (64.0 mg).

Workup

  1. customThe insoluble material was removed by filtration
  2. concentrationthe filtrate was concentrated in vacuo
  3. customThe residue was purified by silica gel column chromatography (EtOAc/hexane)
  4. additionTo the mixture of the crude material and THF (1 mL)
  5. additionwas added 1N NaOH (1 mL) at room temperature for 12 h
  6. customwas neutralized with 1N HCl at 0° C.
  7. extractionextracted with EtOAc
  8. customThe organic layer was separated
  9. washwashed successively with water and brine
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated in vacuo
  12. customThe solid was crystallized from EtOAc-hexane

Sources & evidence

ORD record
ord-4951a2f81ee34efc9ef0ce721aae98d6
Source dataset
uspto-grants-2016_01
Patent number
US09238639B2

Reaction notes

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