Tributylphosphine → Ethyl 3-cyclopropyl-3-(6-((5-(2-fluoro-5-methoxyphenyl)-4-isobutoxypyridin-2-yl)methoxy)pyrimidin-4-yl)propanoate

HRID 709627Notes

Reaction equation

HRID 709627 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:33]2[CH:38]=[C:37](O)[N:36]=[CH:35][N:34]=2)[CH2:27][C:28]([O:30][CH2:31][CH3:32])=[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:33]2[CH:38]=[C:37]([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)[N:36]=[CH:35][N:34]=2)[CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:25][CH2:24]1

Participants

7

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 117760256(5-(2-Fluoro-5-methoxyphenyl)-4-isobutoxypyridin-2-yl)methanolHCID 178471101ethyl 3-cyclopropyl-3-(4-oxo-1H-pyrimidin-6-yl)propanoate

Product 1

HCID 117760016Ethyl 3-cyclopropyl-3-(6-((5-(2-fluoro-5-methoxyphenyl)-4-isobutoxypyridin-2-yl)methoxy)pyrimidin-4-yl)propanoateYield 22.7%

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 (200 mg) and ethyl 3-cyclopropyl-3-(6-hydroxypyrimidin-4-yl)propanoate (155 mg) in toluene (9.4 mL) were added 1,1′-(azodicarbonyl)dipiperidine (264 mg) and tributylphosphine (261 μL), and the mixture was stirred at room temperature for 24 hr. Hexane/ethyl acetate (1:1) was added to the reaction mixture, the resulting precipitate was filtered off, and the solvent in the filtrate was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (78 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-3ae58888745b4629b6fd9091914b4644
Source dataset
uspto-grants-2015_11
Patent number
US09181186B2

Reaction notes

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