Triethylamine → 6-{4-Chloro-3-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-nicotinic acid methyl ester

HRID 1095954Notes

Reaction equation

HRID 1095954 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[CH:9]([CH3:23])[C:10]([C:16]1[CH:21]=[CH:20][N:19]=[C:18]([Cl:22])[CH:17]=1)([OH:15])[C:11]([F:14])([F:13])[F:12].[CH3:24][O:25][C:26](=[O:34])[C:27]1[CH:32]=[CH:31][C:30](Cl)=[N:29][CH:28]=1.C(N(CC)CC)C.N12CCN(CC1)CC2>CN(C=O)C.O>[CH3:24][O:25][C:26](=[O:34])[C:27]1[CH:32]=[CH:31][C:30]([O:8][C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([CH:9]([CH3:23])[C:10]([C:16]3[CH:21]=[CH:20][N:19]=[C:18]([Cl:22])[CH:17]=3)([OH:15])[C:11]([F:14])([F:13])[F:12])[CH:4]=2)=[N:29][CH:28]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 9237DabcoHCID 254249Methyl 6-chloropyridine-3-carboxylateHCID 252546034-Chloro-3-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenol

Product 1

HCID 723105956-{4-Chloro-3-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-nicotinic acid methyl esterYield 25%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

4-Chloro-3-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenol (obtained in Example 130, step 7) was added to a solution of methyl-6-chloro-nicotinate (41 mg, [CAS Reg. No. 73781-91-6]) in DMF (0.6 mL) followed by the addition of triethylamine (0.021 mL). Stirring was continued for 10 minutes at r.t. Then 1,4-diazabicyclo[2.2.2]octane (1.9 mg) was added and the mixture was stirred over night at r.t. The reaction mixture was poured into water, extracted with ethyl acetate and the organic layer was washed with brine, dried over Na2SO4 and evaporated. The residue was purified by flash chromatography (silica gel, ethyl acetate:heptane=3:7) to give the desired compound as a colorless gum (14 mg, 25%). MS (neg. ion, m/e)=499.1 [(M−H)−].

Workup

  1. stirringthe mixture was stirred over night at r.t
  2. extractionextracted with ethyl acetate
  3. washthe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customThe residue was purified by flash chromatography (silica gel, ethyl acetate:heptane=3:7)

Sources & evidence

ORD record
ord-c7cb48a8af8e47c9b531816a92a97480
Source dataset
uspto-grants-2012_03
Patent number
US08138189B2

Reaction notes

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