Hydrochloric Acid → 5-(4-Methyl-piperazin-1-ylmethyl)-1,3-dihydro-isoindole-2-carboxylic acid benzyl ester dihydrochloride salt

HRID 334986ノート

反応式

HRID 334986 の反応式
[CH2:1]([O:8][C:9]([N:11]1[CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH2:20]OS(C)(=O)=O)[CH:17]=2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[CH3:32][N:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1.[ClH:39].CO>CC(C)=O>[ClH:39].[ClH:39].[CH2:1]([O:8][C:9]([N:11]1[CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH2:20][N:36]3[CH2:37][CH2:38][N:33]([CH3:32])[CH2:34][CH2:35]3)[CH:17]=2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

7

反応物 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 11430Potassium CarbonateHCID 531671-MethylpiperazineHCID 579902125-Methanesulfonyloxymethyl-1,3-dihydro-isoindole-2-carboxylic acid benzyl ester

生成物 1

HCID 668965095-(4-Methyl-piperazin-1-ylmethyl)-1,3-dihydro-isoindole-2-carboxylic acid benzyl ester dihydrochloride salt収率 65%

試薬・触媒・溶媒 1

HCID 180Acetone溶媒2 回

反応条件

温度
15 °C

実験手順

The solid from Step 8 (assume 0.232 mol) was dissolved in acetone (700 mL) and this solution was added over 45 mins to a cooled (internal temp 15-17° C.) suspension of K2CO3 (48 g) and N-methylpiperazine (50 mL, 0.45 mol) in acetone (330 mL). The suspension was stirred at 15° C. for 3 h (complete removal of starting material by tlc) when the solution was evaporated to a small volume and the residue partition between EtOAc (1000 mL) and a mixture of water (500 mL) and saturated brine (50 mL). The organic phase was washed with a mixture of water (500 mL) and saturated brine (150 mL) and finally washed with saturated brine (300 mL). The solution was dried (MgSO4) and filtered and to this solution was added 1M-HCl in MeOH (430 mL, 0.43 mol). The suspension was cooled (0° C. for 30 mins) and the solid removed by filtration which was washed with EtOAc and then heptane on the sinter and the solid dried (oil-pump, RT 72 h) to give crop 1 of the title compound 66.34 g (65%) as a colourless solid. 1H NMR (400 MHz, Me-d3-OD): 7.64-7.51 (m, 2H), 7.51-7.29 (m, 6H), 5.23 (s, 2H), 4.79 (dd, J=16.2, 6.1 Hz, 4H), 4.49 (s, 2H), 3.66 (s, 8H), 3.03 (s, 3H).

後処理

  1. additionthis solution was added over 45 mins to
  2. temperaturea cooled
  3. custom(complete removal of starting material by tlc) when the solution
  4. customwas evaporated to a small volume
  5. customthe residue partition between EtOAc (1000 mL)
  6. additiona mixture of water (500 mL) and saturated brine (50 mL)
  7. washThe organic phase was washed with a mixture of water (500 mL) and saturated brine (150 mL)
  8. washfinally washed with saturated brine (300 mL)
  9. dry with materialThe solution was dried (MgSO4)
  10. filtrationfiltered and to this solution
  11. temperatureThe suspension was cooled (0° C. for 30 mins)
  12. customthe solid removed by filtration which
  13. washwas washed with EtOAc
  14. dry with materialheptane on the sinter and the solid dried (oil-pump, RT 72 h)

出典と根拠

ORDレコード
ord-cc13d49344b84092b8520fcad59d1db0
出典データセット
uspto-grants-2014_11
特許番号
US08883790B2

反応ノート

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