Tris(hydroxymethyl)aminomethane → Methyl 2-[(4-{3-[(3-ethoxypropyl)(4-isopropylbenzyl)amino]-3-oxopropyl}phenoxy)methyl]benzoate

HRID 899890ノート

反応式

HRID 899890 の反応式
[CH2:1]([O:3][CH2:4][CH2:5][CH2:6][N:7]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([CH:26]([CH3:28])[CH3:27])=[CH:22][CH:21]=1)[C:8](=[O:18])[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)[CH3:2].Br[CH2:30][C:31]1[CH:40]=[CH:39][CH:38]=[CH:37][C:32]=1[C:33]([O:35][CH3:36])=[O:34].C(=O)([O-])[O-].[K+].[K+].C(O)C(N)(CO)CO>C(#N)C>[CH2:1]([O:3][CH2:4][CH2:5][CH2:6][N:7]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([CH:26]([CH3:27])[CH3:28])=[CH:22][CH:21]=1)[C:8](=[O:18])[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:30][C:31]2[CH:40]=[CH:39][CH:38]=[CH:37][C:32]=2[C:33]([O:35][CH3:36])=[O:34])=[CH:13][CH:12]=1)[CH3:2]

参加物

6

反応物 4

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 11430Potassium CarbonateHCID 2734813Methyl 2-(bromomethyl)benzoateHCID 69120692N-(3-ethoxypropyl)-3-(4-hydroxyphenyl)-N-(4-isopropylbenzyl)propanamide

生成物 1

HCID 69134058Methyl 2-[(4-{3-[(3-ethoxypropyl)(4-isopropylbenzyl)amino]-3-oxopropyl}phenoxy)methyl]benzoate収率 64%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
60 °C

実験手順

N-(3-ethoxypropyl)-3-(4-hydroxyphenyl)-N-(4-isopropylbenzyl)propanamide (0.18 g, 0.47 mmol) and methyl 2-(bromomethyl)benzoate (0.12 g, 0.52 mmol) was dissolved in acetonitrile (10 ml) and potassium carbonate (131 mg, 0.95 mmol) was added. The mixture was stirred at 60° C. for three hours. Polymer-supported trisamine (0.3 eqv) was added and stirred overnight. The polymer was filtered off, solvent was removed by evaporation, addition of EtOAc (10 ml) and the organic phase was washed with three portions of water. After drying the crude (MgSO4) and the solvent had been removed by evaporation, the crude was purified by preparative HPLC (started with acetonitrile/buffer 60/40 and then the acetonitrile concentration was increased to 100%, the buffer was a mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min). The product containing fractions were pooled and the acetonitrile was removed by evaporation. EtOAc (10 ml) was added and the organic phase was washed with two potions of brine and dried (MgSO4). Removing the solvent by evaporation gave 0.16 gram of methyl 2-[(4-{3-[(3-ethoxypropyl)(4-isopropylbenzyl)amino]-3-oxopropyl}phenoxy)methyl]benzoate (yield 63.5%).

後処理

  1. stirringstirred overnight
  2. filtrationThe polymer was filtered off
  3. customsolvent was removed by evaporation, addition of EtOAc (10 ml)
  4. washthe organic phase was washed with three portions of water
  5. dry with materialAfter drying the crude (MgSO4)
  6. customthe solvent had been removed by evaporation
  7. customthe crude was purified by preparative HPLC (
  8. concentrationthe acetonitrile concentration
  9. temperaturewas increased to 100%
  10. additiona mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min)
  11. additionThe product containing fractions
  12. customthe acetonitrile was removed by evaporation
  13. additionEtOAc (10 ml) was added
  14. washthe organic phase was washed with two potions of brine
  15. dry with materialdried (MgSO4)
  16. customRemoving the solvent
  17. customby evaporation

出典と根拠

ORDレコード
ord-c706ddc2a87c438a9a6e210cc9197233
出典データセット
uspto-grants-2008_04
特許番号
US07355069B2

反応ノート

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