Hydrochloric Acid → 5-(3-Chloro-4-fluorophenyl)-6-(2,2,2-trifluoroethoxy)nicotinic acid

HRID 1025983

反応式

HRID 1025983 の反応式
Br[C:2]1[CH:3]=[C:4]([C:14]([OH:16])=[O:15])[CH:5]=[N:6][C:7]=1[O:8][CH2:9][C:10]([F:13])([F:12])[F:11].[Cl:17][C:18]1[CH:19]=[C:20](B(O)O)[CH:21]=[CH:22][C:23]=1[F:24].C([O-])([O-])=O.[Na+].[Na+].Cl>C1(C)C=CC=CC=1.CN(C=O)C>[Cl:17][C:18]1[CH:19]=[C:20]([C:2]2[C:7]([O:8][CH2:9][C:10]([F:13])([F:12])[F:11])=[N:6][CH:5]=[C:4]([CH:3]=2)[C:14]([OH:16])=[O:15])[CH:21]=[CH:22][C:23]=1[F:24]

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 27346603-Chloro-4-fluorophenylboronic Acid (contains varying amounts of Anhydride)HCID 581925925-Bromo-6-(2,2,2-trifluoroethoxy)-3-pyridinecarboxylic acid

生成物 1

HCID 666788425-(3-Chloro-4-fluorophenyl)-6-(2,2,2-trifluoroethoxy)nicotinic acid収率 63%

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
90 °C

実験手順

5-Bromo-6-(2,2,2-trifluoroethoxy)-3-pyridinecarboxylic acid (CAN 1211586-75-2; 1.5 g; 5.0 mmol) was dissolved in toluene (35 mL) an DMF (2 mL). To this solution was added 1,1′-bis(diphenylphosphino)-ferrocene-palladium(II)dichloride dichloromethane complex (204 mg, 250 μmol), followed by 3-chloro-4-fluorophenylboronic acid (CAN 144432-85-9; 959 mg, 5.5 mmol) and 2M—Na2CO3 (20.0 ml, 40.0 mmol). The reaction mixture was heated to 90° C. and stirred for 4 h, cooled and poured into 100 mL ice water, acidified with 45 mL 2N—HCl and extracted ethyl acetate. The organic layers were combined, dried with Na2SO4 and concentrated in vacuo. The crude material was crystallized from heptane:ethyl acetate (5:1) to yield 1.1 g (63%) of the title compound as light grey solid; LC-MS (UV peak area/ESI): 97%, 348.0066 (M−H)−.

後処理

  1. additionTo this solution was added 1,1′-bis(diphenylphosphino)-ferrocene-palladium(II)dichloride dichloromethane complex (204 mg, 250 μmol)
  2. temperaturecooled
  3. extractionextracted ethyl acetate
  4. dry with materialdried with Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude material was crystallized from heptane:ethyl acetate (5:1)

出典と根拠

ORDレコード
ord-1594cc1689c24116879ad165bd283b5f
出典データセット
uspto-grants-2014_05
特許番号
US08729105B2

関連ノート

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