Potassium Phosphate, Tribasic → 2-Chloro-4-cyclopropyl-5-methyl-6-fluoroaniline

HRID 1270734ノート

反応式

HRID 1270734 の反応式
[Cl:1][C:2]1[CH:8]=[C:7](Br)[C:6]([CH3:10])=[C:5]([F:11])[C:3]=1[NH2:4].[CH:12]1(B(O)O)[CH2:14][CH2:13]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>COCCOC.O>[Cl:1][C:2]1[CH:8]=[C:7]([CH:12]2[CH2:14][CH2:13]2)[C:6]([CH3:10])=[C:5]([F:11])[C:3]=1[NH2:4]

参加物

6

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 184515002-Chloro-4-bromo-5-methyl-6-fluoroaniline

生成物 1

HCID 184515032-Chloro-4-cyclopropyl-5-methyl-6-fluoroaniline

試薬・触媒・溶媒 1

HCID 18180031Water 1,2-dimethoxyethane溶媒

実験手順

2-Chloro-4-bromo-5-methyl-6-fluoroaniline (6.5 g, 27 mmol), cyclopropylboronic acid (2.8 g, 33 mmol), tetrakis (triphenylphosphine)palladium (0) (1.4 g, 1.3 mmol), potassium phosphate (20.2 g, 95 mmol) and tricyclohexylphosphine (0.77 g, 2.7 mmol) are combined and stirred in 200 mL of a 4:1 DME/water solution. The mixture is degassed by repeated alternating application of vacuum and positive nitrogen pressure (10×). The mixture is heated to reflux temperature for 2 days and then cooled to room temperature. Most of the DME is removed by rotary evaporator and the residual mixture is partitioned between Et2O (250 mL) and water (250 mL). The organic phase is washed with brine (3×250 mL), dried (MgSO4) and concentrated by rotary evaporator. The crude product is purified using flash chromatography (8% CH2Cl2/hexanes) to give 2-chloro-4-cyclopropyl-5-methyl-6-fluoroaniline as a tan oil.

後処理

  1. customThe mixture is degassed by repeated alternating application of vacuum and positive nitrogen pressure (10×)
  2. temperatureThe mixture is heated
  3. temperatureto reflux temperature for 2 days
  4. customMost of the DME is removed by rotary evaporator
  5. customthe residual mixture is partitioned between Et2O (250 mL) and water (250 mL)
  6. washThe organic phase is washed with brine (3×250 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated by rotary evaporator
  9. customThe crude product is purified

出典と根拠

ORDレコード
ord-2baa8c18e5704287afaadc91bd50569f
出典データセット
uspto-grants-2007_04
特許番号
US07202364B2

反応ノート

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