Tributylphosphine → Methyl(4-fluoro-6-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methoxy)-1-benzothiophen-3-yl)acetate

HRID 591565Notes

Reaction equation

HRID 591565 reaction equation
C(P(CCCC)CCCC)CCC.[CH3:14][C:15]1[C:20]([CH2:21][OH:22])=[CH:19][CH:18]=[C:17]([C:23]([F:26])([F:25])[F:24])[N:16]=1.[CH3:27][O:28][C:29](=[O:42])[CH2:30][C:31]1[C:35]2[C:36]([F:41])=[CH:37][C:38](O)=[CH:39][C:34]=2[S:33][CH:32]=1.C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1>C1COCC1>[CH3:27][O:28][C:29](=[O:42])[CH2:30][C:31]1[C:35]2[C:36]([F:41])=[CH:37][C:38]([O:22][CH2:21][C:20]3[C:15]([CH3:14])=[N:16][C:17]([C:23]([F:24])([F:26])[F:25])=[CH:18][CH:19]=3)=[CH:39][C:34]=2[S:33][CH:32]=1

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 2760122(2-Methyl-6-(trifluoromethyl)pyridin-3-yl)methanolHCID 129359611Methyl(4-fluoro-6-hydroxy-1-benzothiophen-3-yl)acetate

Product 1

HCID 118667067Methyl(4-fluoro-6-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methoxy)-1-benzothiophen-3-yl)acetateYield 85.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of tri-n-butylphosphine (0.655 mL), (2-methyl-6-(trifluoromethyl)pyridin-3-yl)methanol (167 mg), methyl(4-fluoro-6-hydroxy-1-benzothiophen-3-yl)acetate (210 mg) and THF (dry) (15 mL) was added ADDP (662 mg, 2.62 mmol) at room temperature. The mixture was stirred at room temperature for 2 h and then concentrated in vacuo. To the residue was added IPE and the insoluble materials were removed by filtration. The filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (NH, EtOAc/hexane) and silica gel column chromatography (EtOAc/hexane) to give the title compound (310 mg). The crystals were recrystallized from acetone-hexane.

Workup

  1. concentrationconcentrated in vacuo
  2. additionTo the residue was added IPE
  3. customthe insoluble materials were removed by filtration
  4. concentrationThe filtrate was concentrated in vacuo
  5. customThe residue was purified by silica gel column chromatography (NH, EtOAc/hexane) and silica gel column chromatography (EtOAc/hexane)

Sources & evidence

ORD record
ord-363270ef8b06459abfeb89f315b7d279
Source dataset
uspto-grants-2016_01
Patent number
US09238639B2

Reaction notes

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