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

HRID 624948ノート

反応式

HRID 624948 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]([C:17]([OH:19])=[O:18])=[N:6][C:7]=1[O:8][CH2:9][C:10]([F:16])([F:15])[C:11]([F:14])([F:13])[F:12].[CH:20]1(B(O)O)[CH2:22][CH2:21]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl>C1(C)C=CC=CC=1.O.C([O-])(=O)C.C([O-])(=O)C.[Pd+2].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>[CH:20]1([C:2]2[CH:3]=[CH:4][C:5]([C:17]([OH:19])=[O:18])=[N:6][C:7]=2[O:8][CH2:9][C:10]([F:16])([F:15])[C:11]([F:14])([F:13])[F:12])[CH2:22][CH2:21]1

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 866747855-Bromo-6-(2,2,3,3,3-pentafluoro-propoxy)-pyridine-2-carboxylic acid

生成物 1

HCID 866747875-Cyclopropyl-6-(2,2,3,3,3-pentafluoro-propoxy)-pyridine-2-carboxylic acid収率 76.4%

試薬・触媒・溶媒 3

HCID 75806Tricyclohexylphosphine触媒HCID 167845palladium(II) acetate触媒HCID 22272177Toluene water溶媒

反応条件

温度
100 °C

実験手順

A mixture of 5-bromo-6-(2,2,3,3,3-pentafluoro-propoxy)-pyridine-2-carboxylic acid (501 mg, 1.43 mmol), cyclopropylboronic acid (CAN 411235-57-9, 184 mg, 2.15 mmol), palladium diacetate (CAN 3375-31-3, 16.1 mg, 71.6 μmol), tricyclohexylphosphine (CAN 2622-14-2, 8.03 mg, 28.6 μmol) and potassium phosphate (1.06 g, 5.01 mmol) in toluene/water (20/1 v/v, 10.5 mL) was stirred at 100° C. for 22 hours. After cooling the mixture was poured into ice-water (80 mL). 2 M Hydrochloric acid (25 mL) was added 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 (340 mg, 76%) as off-white solid; LC-MS (UV peak area, ESI) 96.6%, 310.0513 [M−H−].

後処理

  1. temperatureAfter cooling the mixture
  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-d2d8320358524fae82af8d903cd1a0e9
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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