Citric Acid → 6-{2-[2-(4-Chloro-phenyl)-2,4,5,6-tetrahydro-cyclopentapyrazol-3-yl]-2-cyclohexyl-ethoxy}-nicotinic acid methyl ester

HRID 889381ノート

反応式

HRID 889381 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH:13]([CH:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)[C:14](NC3CCCCC3)=[O:15])=[C:11]3[CH2:29][CH2:30][CH2:31][C:10]3=[N:9]2)=[CH:4][CH:3]=1.[C:32]([O-])([O-])=[O:33].[K+].[K+].ClC1C=CC([N:45]2[C:49]([CH:50]([CH:57]3[CH2:62][CH2:61]CCC3)[CH2:51][O:52]S(C)(=O)=O)=C3CCCC3=N2)=CC=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C.CCOC(C)=O>[CH3:32][O:33][C:51](=[O:52])[C:50]1[CH:57]=[CH:62][C:61]([O:15][CH2:14][CH:13]([C:12]2[N:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)[N:9]=[C:10]3[CH2:31][CH2:30][CH2:29][C:11]=23)[CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)=[N:45][CH:49]=1

参加物

7

反応物 4

HCID 311Citric AcidHCID 11430Potassium CarbonateHCID 533902542-[2-(4-Chloro-phenyl)-2,4,5,6-tetrahydro-cyclopentapyrazol-3-yl]-2,N-dicyclohexyl-acetamideHCID 86657984Methanesulfonic acid 2-[2-(4-chloro-phenyl)-2,4,5,6-tetrahydro-cyclopentapyrazol-3-yl]-2-cyclohexyl-ethyl ester

生成物 1

HCID 673871806-{2-[2-(4-Chloro-phenyl)-2,4,5,6-tetrahydro-cyclopentapyrazol-3-yl]-2-cyclohexyl-ethoxy}-nicotinic acid methyl ester収率 67%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

To a solution of methyl 6-hydroxynicotinate 4 (80 mg, 0.19 mmol; CAS Reg. No. 10128-91-3) in dry DMF (3 ml) was added dry K2CO3 (29 mg, 0.226 mmol) at 0° C. The reaction mixture was stirred for 15 minutes at 0° C. Methanesulfonic acid 2-[2-(4-chloro-phenyl)-2,4,5,6-tetrahydro-cyclopentapyrazol-3-yl]-2-cyclohexyl-ethyl ester (35 mg, 0.227 mmol) dissolved in dry DMF (1 ml) was added at 0° C. The reaction mixture was heated to 100° C. in a sealed tube for 12 h. 10% Aqueous citric acid solution (10 ml) and EtOAc (5 ml) were added to the reaction mixture. The layers were separated and the aqueous layer was extracted one more time with EtOAc (5 ml). The combined organic layers were washed with brine (5 ml) and dried over Na2SO4. The solvent was removed under reduced pressure to give a residue which was purified by column chromatography over silica gel (20% EtOAc/hexane) to give the title compound (60.2 mg, 0.12 mmol; 67%) as off-white solid.

後処理

  1. additionwas added at 0° C
  2. temperatureThe reaction mixture was heated to 100° C. in a sealed tube for 12 h
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted one more time with EtOAc (5 ml)
  5. washThe combined organic layers were washed with brine (5 ml)
  6. dry with materialdried over Na2SO4
  7. customThe solvent was removed under reduced pressure
  8. customto give a residue which
  9. customwas purified by column chromatography over silica gel (20% EtOAc/hexane)

出典と根拠

ORDレコード
ord-c16aff626632482693e797bb76495245
出典データセット
uspto-grants-2012_08
特許番号
US08252826B2

反応ノート

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