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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 1095954
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HRID 1095954 반응식
[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
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참가 물질

7

반응물 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

생성물 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 ester수율 25%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

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)−].

후처리

  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)

출처 및 근거

ORD 기록
ord-c7cb48a8af8e47c9b531816a92a97480
출처 데이터셋
uspto-grants-2012_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08138189B2

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