Tributylphosphine → Methyl 3-cyclopropyl-3-(3-((6-(2,2-dimethylpropyl)-5-(2-fluoro-5-methoxyphenyl)pyridin-2-yl)methoxy)-4-methoxyphenyl)propanoate

HRID 709654Notes

Reaction equation

HRID 709654 reaction equation
[CH:1]1([CH:4]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([OH:18])[CH:11]=2)[CH2:5][C:6]([O:8][CH3:9])=[O:7])[CH2:3][CH2:2]1.[CH3:19][C:20]([CH3:40])([CH3:39])[CH2:21][C:22]1[N:27]=[C:26]([CH2:28]O)[CH:25]=[CH:24][C:23]=1[C:30]1[CH:35]=[C:34]([O:36][CH3:37])[CH:33]=[CH:32][C:31]=1[F:38].N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC>C1(C)C=CC=CC=1.C(OCC)(=O)C.CCCCCC>[CH:1]1([CH:4]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH2:28][C:26]3[CH:25]=[CH:24][C:23]([C:30]4[CH:35]=[C:34]([O:36][CH3:37])[CH:33]=[CH:32][C:31]=4[F:38])=[C:22]([CH2:21][C:20]([CH3:40])([CH3:39])[CH3:19])[N:27]=3)[CH:11]=2)[CH2:5][C:6]([O:8][CH3:9])=[O:7])[CH2:2][CH2:3]1

Participants

8

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 117759814(5-(2-Fluoro-5-methoxyphenyl)-6-neopentylpyridin-2-yl)methanolHCID 117760009Methyl 3-cyclopropyl-3-(3-hydroxy-4-methoxyphenyl)propanoate

Product 1

HCID 117759994Methyl 3-cyclopropyl-3-(3-((6-(2,2-dimethylpropyl)-5-(2-fluoro-5-methoxyphenyl)pyridin-2-yl)methoxy)-4-methoxyphenyl)propanoateYield 53.3%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Under a nitrogen atmosphere, to a solution of methyl 3-cyclopropyl-3-(3-hydroxy-4-methoxyphenyl)propanoate (168 mg) and (6-(2,2-dimethylpropyl)-5-(2-fluoro-5-methoxyphenyl)pyridin-2-yl)methanol (202 mg) in toluene (15 mL) were added 1,1′-(azodicarbonyl)dipiperidine (268 mg) and tributylphosphine (262 and the mixture was stirred at room temperature for 15 hr. Hexane and ethyl acetate were added to the reaction mixture, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (190 mg) as a colorless oil.

Workup

  1. filtrationthe insoluble material was filtered off
  2. concentrationThe filtrate was concentrated under reduced pressure
  3. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-8447ccedba1b450db95678f0f08521ad
Source dataset
uspto-grants-2015_11
Patent number
US09181186B2

Reaction notes

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