Triethylamine → 2-Chloro-6-{3-chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-5-yl)-propyl]-phenoxy}-nicotinic acid methyl ester

HRID 2386864Notes

Reaction equation

HRID 2386864 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[CH:9]([CH3:27])[C:10]([C:16]1[CH:17]=[CH:18][C:19]2[O:23][C:22](=[O:24])[N:21]([CH3:25])[C:20]=2[CH:26]=1)([OH:15])[C:11]([F:14])([F:13])[F:12].[CH3:28][O:29][C:30]([C:32]1[C:33]([Cl:39])=[N:34][C:35](Cl)=[CH:36][CH:37]=1)=[O:31].C(N(CC)CC)C.N12CCN(CC1)CC2>CN(C=O)C.O>[CH3:28][O:29][C:30](=[O:31])[C:32]1[CH:37]=[CH:36][C:35]([O:8][C:6]2[CH:5]=[CH:4][C:3]([CH:9]([CH3:27])[C:10]([OH:15])([C:16]3[CH:17]=[CH:18][C:19]4[O:23][C:22](=[O:24])[N:21]([CH3:25])[C:20]=4[CH:26]=3)[C:11]([F:12])([F:13])[F:14])=[C:2]([Cl:1])[CH:7]=2)=[N:34][C:33]=1[Cl:39]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 9237DabcoHCID 11106516Methyl 2,6-dichloropyridine-3-carboxylateHCID 666969865-[2-(2-Chloro-4-hydroxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-3-methyl-3H-benzooxazol-2-one

Product 1

HCID 723101372-Chloro-6-{3-chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-5-yl)-propyl]-phenoxy}-nicotinic acid methyl esterYield 87%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

5-[2-(2-Chloro-4-hydroxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-3-methyl-3H-benzooxazol-2-one (157 mg, obtained in Example 172) was added to a solution of methyl-2,6-dichloropyridine-3-carboxylate (81 mg, [CAS Reg. No. 65515-28-8]) in DMF (3 mL) followed by the addition of triethylamine (0.071 mL). Stirring was continued for 10 minutes at r.t. Then 1,4-diazabicyclo[2.2.2]octane (7 mg) was added. 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, gradient of heptane in ethyl acetate) to give the desired compound as a colorless foam (195 mg, 87%). MS (neg. ion, m/e)=569.2 [(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, gradient of heptane in ethyl acetate)

Sources & evidence

ORD record
ord-9463c1bda3ef4816b4a58ce1843753bb
Source dataset
uspto-grants-2012_09
Patent number
US08268820B2

Reaction notes

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