Hydrochloric Acid → 5-Bromo-6-(2,2,3,3,3-pentafluoro-propoxy)-pyridine-2-carboxylic acid

HRID 624947ノート

反応式

HRID 624947 の反応式
Cl[C:2]1[N:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[CH:4][C:3]=1[Br:11].CC(C)([O-])C.[K+].[F:18][C:19]([F:26])([C:22]([F:25])([F:24])[F:23])[CH2:20][OH:21].Cl>CN(C=O)C.C1COCC1>[Br:11][C:3]1[CH:4]=[CH:5][C:6]([C:8]([OH:10])=[O:9])=[N:7][C:2]=1[O:21][CH2:20][C:19]([F:26])([F:18])[C:22]([F:25])([F:24])[F:23]

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 98722,2,3,3,3-PentafluoropropanolHCID 23665647Potassium tert-butoxideHCID 446077145-Bromo-6-chloropicolinic acid

生成物 1

HCID 866747855-Bromo-6-(2,2,3,3,3-pentafluoro-propoxy)-pyridine-2-carboxylic acid収率 22%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
140 °C

実験手順

To a solution of 6-chloro-5-bromo-pyridine-2-carboxylic acid (CAN 959958-25-9, 1.7 g, 7.19 mmol) in DMF (90 mL) and THF (30 mL) was added potassium tert-butoxide (2.02 g, 18.0 mmol) and 2,2,3,3,3-pentafluoropropan-1-ol (5.73 mL, 57.5 mmol). The mixture was stirred at 140° C. for 4 days, cooled and poured into ice-water (100 mL). 2 M Hydrochloric acid (15 mL) was added to adjust the pH to 2-3 and the mixture was extracted with TBME, organic layers were washed twice with water, pooled, dried with Na2SO4, filtered and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, ethyl acetate/n-heptane gradient) to give the title compound (548 mg, 22%) as light-brown solid; LC-MS (UV peak area, ESI) 100%, 347.9306 [M−H−].

後処理

  1. temperaturecooled
  2. extractionthe mixture was extracted with TBME, organic layers
  3. washwere washed twice with water
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by flash chromatography (silica gel, ethyl acetate/n-heptane gradient)

出典と根拠

ORDレコード
ord-d68ba1923fc0461798d28d9c00cef0c1
出典データセット
uspto-grants-2016_04
特許番号
US09303012B2

反応ノート

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