Tributylphosphine → Methyl 3-cyclopropyl-3-(3-((5-(2-fluoro-5-methoxyphenyl)-4-isobutoxypyridin-2-yl)methoxy)phenyl)propanoate

HRID 709625Notes

Reaction equation

HRID 709625 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[C:11]([O:18][CH2:19][CH:20]([CH3:22])[CH3:21])=[CH:12][C:13]([CH2:16][OH:17])=[N:14][CH:15]=1.[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:17][CH2:16][C:13]3[CH:12]=[C:11]([O:18][CH2:19][CH:20]([CH3:22])[CH3:21])[C:10]([C:3]4[CH:4]=[C:5]([O:8][CH3:9])[CH:6]=[CH:7][C:2]=4[F:1])=[CH:15][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 117760256(5-(2-Fluoro-5-methoxyphenyl)-4-isobutoxypyridin-2-yl)methanol

Product 1

HCID 117760220Methyl 3-cyclopropyl-3-(3-((5-(2-fluoro-5-methoxyphenyl)-4-isobutoxypyridin-2-yl)methoxy)phenyl)propanoateYield 84.9%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

Under a nitrogen atmosphere, to a solution of (5-(2-fluoro-5-methoxyphenyl)-4-isobutoxypyridin-2-yl)methanol (214 mg) and methyl 3-cyclopropyl-3-(3-hydroxyphenyl)propanoate (155 mg) in toluene (10 mL) were added 1,1′-(azodicarbonyl)dipiperidine (283 mg) and tributylphosphine (280 μL), and the mixture was stirred at room temperature overnight. 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 (302 mg) as a colorless amorphous solid.

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-72bcb17772e54e7ba9697a85f532c819
Source dataset
uspto-grants-2015_11
Patent number
US09181186B2

Reaction notes

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