Tributylphosphine → Methyl 3-cyclopropyl-3-(3-((5-(2-fluoro-5-methoxyphenyl)-6-isobutoxypyridin-2-yl)methoxy)phenyl)propanoate

HRID 709604Notes

Reaction equation

HRID 709604 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:11]=[CH:12][C:13]([CH2:21][OH:22])=[N:14][C:15]=1[O:16][CH2:17][CH:18]([CH3:20])[CH3:19].[CH:23]1([CH:26]([C:32]2[CH:37]=[CH:36][CH:35]=[C:34](O)[CH:33]=2)[CH2:27][C:28]([O:30][CH3:31])=[O:29])[CH2:25][CH2:24]1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC>C1(C)C=CC=CC=1.CCCCCC.C(OCC)(=O)C>[CH:23]1([CH:26]([C:32]2[CH:33]=[CH:34][CH:35]=[C:36]([O:22][CH2:21][C:13]3[CH:12]=[CH:11][C:10]([C:3]4[CH:4]=[C:5]([O:8][CH3:9])[CH:6]=[CH:7][C:2]=4[F:1])=[C:15]([O:16][CH2:17][CH:18]([CH3:19])[CH3:20])[N:14]=3)[CH:37]=2)[CH2:27][C:28]([O:30][CH3:31])=[O:29])[CH2:24][CH2:25]1

Participants

7

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 57706598Methyl 3-Cyclopropyl-3-(3-hydroxyphenyl)propanoateHCID 117760235(5-(2-Fluoro-5-methoxyphenyl)-6-isobutoxypyridin-2-yl)methanol

Product 1

HCID 117760024Methyl 3-cyclopropyl-3-(3-((5-(2-fluoro-5-methoxyphenyl)-6-isobutoxypyridin-2-yl)methoxy)phenyl)propanoateYield 79%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

Under a nitrogen atmosphere, to a solution of (5-(2-fluoro-5-methoxyphenyl)-6-isobutoxypyridin-2-yl)methanol (100 mg) and methyl 3-cyclopropyl-3-(3-hydroxyphenyl)propanoate (72 mg) in toluene (4.7 mL) were added 1,1′-(azodicarbonyl)dipiperidine (132 mg) and tributylphosphine (131 μL), and the mixture was stirred at room temperature for 14 hr. To the reaction mixture was added hexane/ethyl acetate (1:1), and the resulting precipitate was removed by filtration. The solvent in the filtrate was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (131 mg) as a colorless oil.

Workup

  1. customthe resulting precipitate was removed by filtration
  2. customThe solvent in the filtrate was evaporated under reduced pressure
  3. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-0c3714d49f2a46ce8a9f8d6047eb9e4e
Source dataset
uspto-grants-2015_11
Patent number
US09181186B2

Reaction notes

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