Hexanal → Methyl 5-[{4-[(4-ethylphenyl)ethynyl]benzyl}(hexyl)amino]-2-fluorobenzoate

HRID 551970ノート

反応式

HRID 551970 の反応式
[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]#[C:10][C:11]2[CH:18]=[CH:17][C:14]([CH:15]=O)=[CH:13][CH:12]=2)=[CH:5][CH:4]=1)[CH3:2].[NH2:19][C:20]1[CH:21]=[CH:22][C:23]([F:30])=[C:24]([CH:29]=1)[C:25]([O:27][CH3:28])=[O:26].[CH:31](=O)[CH2:32][CH2:33][CH2:34][CH2:35][CH3:36].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1.C(O)(=O)C.O>[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]#[C:10][C:11]2[CH:18]=[CH:17][C:14]([CH2:15][N:19]([CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])[C:20]3[CH:21]=[CH:22][C:23]([F:30])=[C:24]([CH:29]=3)[C:25]([O:27][CH3:28])=[O:26])=[CH:13][CH:12]=2)=[CH:5][CH:4]=1)[CH3:2]

参加物

9

反応物 5

HCID 6184HexanalHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 112763804-[(4-Ethylphenyl)ethynyl]benzaldehydeHCID 15621043Methyl 5-amino-2-fluorobenzoate

生成物 1

HCID 57554472Methyl 5-[{4-[(4-ethylphenyl)ethynyl]benzyl}(hexyl)amino]-2-fluorobenzoate収率 131.4%

試薬・触媒・溶媒 3

HCID 176Acetic Acid溶媒2 回HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
60 °C

実験手順

To a solution of 4-[(4-ethylphenyl)ethynyl]benzaldehyde (530 mg; 2.26 mmol, intermediate which may be prepared according to methods disclosed in EP03103780.7) in toluene (35 mL) were added methyl 5-amino-2-fluorobenzoate (382 mg; 2.26 mmol) and AcOH (194 μL) and the reaction mixture was refluxed with azeotropic removal of water until complete consumption of, the aldehyde (determined by 1H NMR of aliquots). Toluene was concentrated under reduced pressure and the residue dissolved in DCE (25 mL). Hexanal (Aldrich, 818 μl; 6.79 mmol), acetic acid (194 μL) and sodium triacetoxyborohydride (1,4 g, 6.79 mmol) were added to the solution, which was then heated at 60° C. for 3 hrs. The reaction mixture was poured into a saturated solution of NaHCO3 and extracted twice with DCM. Combined organic layers were washed with brine, dried over magnesium sulfate, filtrated and concentrated to give 1.4 g of a brown solid. Purification by flash chromatography using silica gel (EtOAc/c-Hex, gradient from 97:3 to 95:5) yielded to 330 mg (30%) of the title compound as a white solid. HPLC, Rt: 6.27 min (purity: 61%), LC/MS, M+(ESI): 472.2, 1H NMR (CDCl3) δ: 7.43 (t, J=7.7 Hz, 4H), 7.17 (m, 5H), 6.90 (t, J=10.7 Hz, 1H), 6.73 (m, 1H), 4.49 (s, 2H), 3.88 (s, 3H), 3.35 (t, J=7.8 Hz, 2H), 2.63 (qd, J=7.5 Hz, 2H), 1.61 (m, 2H), 1.28 (m, 6H), 1.22 (t, J=7.6 Hz, 3H), 0.85 (t, J=5.1 Hz, 3H).

後処理

  1. concentrationToluene was concentrated under reduced pressure
  2. dissolutionthe residue dissolved in DCE (25 mL)
  3. extractionextracted twice with DCM
  4. washCombined organic layers were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltrated
  7. concentrationconcentrated

出典と根拠

ORDレコード
ord-5696c77c09d14cf7b3fa7df6adbfee78
出典データセット
uspto-grants-2011_05
特許番号
US07947851B2

反応ノート

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