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

HRID 709772Notes

Reaction equation

HRID 709772 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[N:15]=[C:14]([O:16][CH3:17])[C:13]([CH2:18][OH:19])=[CH:12][C:11]=1[O:20][CH2:21][CH:22]([CH3:24])[CH3:23].[CH:25]1([CH:28]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36](O)[CH:35]=2)[CH2:29][C:30]([O:32][CH3:33])=[O:31])[CH2:27][CH2:26]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:25]1([CH:28]([C:34]2[CH:35]=[CH:36][CH:37]=[C:38]([O:19][CH2:18][C:13]3[C:14]([O:16][CH3:17])=[N:15][C:10]([C:3]4[CH:4]=[C:5]([O:8][CH3:9])[CH:6]=[CH:7][C:2]=4[F:1])=[C:11]([O:20][CH2:21][CH:22]([CH3:24])[CH3:23])[CH:12]=3)[CH:39]=2)[CH2:29][C:30]([O:32][CH3:33])=[O:31])[CH2:26][CH2:27]1

Participants

7

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 57706598Methyl 3-Cyclopropyl-3-(3-hydroxyphenyl)propanoateHCID 117760272(6-(2-Fluoro-5-methoxyphenyl)-5-isobutoxy-2-methoxypyridin-3-yl)methanol

Product 1

HCID 117759912Methyl 3-cyclopropyl-3-(3-((6-(2-fluoro-5-methoxyphenyl)-5-isobutoxy-2-methoxypyridin-3-yl)methoxy)phenyl)propanoateYield 79.6%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

Under a nitrogen atmosphere, to a solution of (6-(2-fluoro-5-methoxyphenyl)-5-isobutoxy-2-methoxypyridin-3-yl)methanol (94 mg) and methyl 3-cyclopropyl-3-(3-hydroxyphenyl)propanoate (62 mg) in toluene (4.0 mL) were added 1,1′-(azodicarbonyl)dipiperidine (113 mg) and tributylphosphine (112 μL), and the mixture was stirred at room temperature for 14 hr. Hexane/ethyl acetate (1:1) was added to the reaction mixture, and the resulting precipitate was filtered off. 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 (120 mg) as a colorless oil.

Workup

  1. filtrationthe resulting precipitate was filtered off
  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-2bf5a31cd9c441cb8482de9fc67b2081
Source dataset
uspto-grants-2015_11
Patent number
US09181186B2

Reaction notes

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