Sodium Bicarbonate → 2-Chloro-5-(3,5-dimethylphenyl)nicotinic acid

HRID 1675936노트

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HRID 1675936 반응식
[Cl:1][C:2]1[N:11]=[CH:10][C:9](I)=[CH:8][C:3]=1[C:4]([O:6]C)=[O:5].[CH3:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[C:18]([CH3:20])[CH:19]=1.C(=O)(O)[O-].[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[N:11]=[CH:10][C:9]([C:16]2[CH:17]=[C:18]([CH3:20])[CH:19]=[C:14]([CH3:13])[CH:15]=2)=[CH:8][C:3]=1[C:4]([OH:6])=[O:5]

참가 물질

6

반응물 3

HCID 516892Sodium BicarbonateHCID 27343493,5-Dimethylphenylboronic acidHCID 2764559Methyl 2-Chloro-5-iodonicotinate

생성물 1

HCID 532227192-Chloro-5-(3,5-dimethylphenyl)nicotinic acid

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 312751,4-Dioxane용매

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온도
90 °C

실험 절차

To a deoxygenated solution of methyl 2-chloro-5-iodonicotinate (1-1, 2.01 g, 6.72 mmol, 1 equiv) and 3,5-dimethylphenylboronic acid (1.01 g, 6.72 mmol. 1.00 equiv) in dioxane (250 mL) was added tetrakis(triphenylphosphine)palladium(0) (155 mg, 0.134 mmol) and 2 N aqueous sodium bicarbonate solution (16.8 mL, 33.6 mmol, 5.00 equiv) and the reaction mixture was heated at 90° C. for 48 hours. The reaction mixture was allowed to cool to 23° C., then partitioned between ethyl acetate (500 mL) and saturated aqueous sodium bicarbonate solution (500 mL). The aqueous layer was filtered and acidified to pH 2 with concentrated hydrochloric acid. The resulting precipitate was collected by filtration washed with water (2×100 mL) and air dried to afford 2-chloro-5-(3,5-dimethylphenyl)nicotinic acid (1-2) as an off white solid. LRMS m/z (M+H) 262.3 found, 262.1 required.

후처리

  1. temperatureto cool to 23° C.
  2. custompartitioned between ethyl acetate (500 mL) and saturated aqueous sodium bicarbonate solution (500 mL)
  3. filtrationThe aqueous layer was filtered
  4. filtrationThe resulting precipitate was collected by filtration
  5. washwashed with water (2×100 mL) and air
  6. customdried

출처 및 근거

ORD 기록
ord-1c74436cddf243959dbb29a72284dee6
출처 데이터셋
uspto-grants-2011_08
특허 번호
US08003797B2

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