Acetic Acid → (5-Chloro-2-dimethylaminomethyl-1H-indol-4-yl)-acetic acid ethyl ester

HRID 1161888ノート

反応式

HRID 1161888 の反応式
COC([N:5]1[C:13]2[C:8](=[C:9]([CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:10]([Cl:14])=[CH:11][CH:12]=2)[CH:7]=[C:6]1[CH:21]=O)=O.[CH3:23][NH:24][CH3:25].C([BH3-])#N.[Na+].C(O)(=O)C.C([O-])(O)=O.[Na+]>C1COCC1.CCO.CO.CCOC(C)=O>[CH2:19]([O:18][C:16](=[O:17])[CH2:15][C:9]1[C:10]([Cl:14])=[CH:11][CH:12]=[C:13]2[C:8]=1[CH:7]=[C:6]([CH2:21][N:24]([CH3:25])[CH3:23])[NH:5]2)[CH3:20]

参加物

10

反応物 5

HCID 176Acetic AcidHCID 674DimethylamineHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 866038735-Chloro-4-ethoxycarbonylmethyl-2-formyl-indole-1-carboxylic acid methyl ester

生成物 1

HCID 66820374(5-Chloro-2-dimethylaminomethyl-1H-indol-4-yl)-acetic acid ethyl ester

試薬・触媒・溶媒 4

HCID 702Ethanol溶媒HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

5-Chloro-4-ethoxycarbonylmethyl-2-formyl-indole-1-carboxylic acid methyl ester (350 mg, 1.08 mmol) is dissolved in dry THF (10 ml) under an atmosphere of argon, and dimethylamine (290 microL of a 5.6 M solution in EtOH, 1.62 mmol) is added at RT. The reaction mixture is stirred at RT for 18 hours. A solution of sodium cyanoborohydride (82 mg, 1.29 mmol) in methanol (3 ml) and acetic acid (310 microL, 5.40 mmol) is then added. Stirring is continued for 3 hours at RT. TLC analysis indicates complete conversion of the starting material. The reaction mixture is diluted with EtOAc and poured on water. The pH is made alkaline by the addition of a saturated aqueous solution of NaHCO3. The aqueous layer is extracted with EtOAc, and the combined organic layers are washed once with concentrated aqueous NaCl solution. After drying over Na2SO4, the solvent is removed and the residue is purified by FCC (CH2Cl2/EtOH/aq. NH3 90:9:1) to give the title compound. 1H NMR (DMSO, 400 MHz) δ 1.19 (t, J=6.6 Hz, 3H), 2.20 (s, 6H), 3.55 (s, 2H), 3.97 (s, 2H), 4.11 (q, J=6.6 Hz, 2H), 6.38 (s, 1H), 7.08 (d, J=9.0 Hz, 1H), 7.26 (d, J=9.0 Hz, 1H), 11.2 (br s, 1H); ES-MS: 293.2 [M+H]−.

後処理

  1. stirringStirring
  2. waitis continued for 3 hours at RT
  3. additionpoured on water
  4. extractionThe aqueous layer is extracted with EtOAc
  5. washthe combined organic layers are washed once with concentrated aqueous NaCl solution
  6. dry with materialAfter drying over Na2SO4
  7. customthe solvent is removed
  8. customthe residue is purified by FCC (CH2Cl2/EtOH/aq. NH3 90:9:1)

出典と根拠

ORDレコード
ord-786cb597bc284f3bb6ccb659d832e6a9
出典データセット
uspto-grants-2010_10
特許番号
US07820672B2

反応ノート

読み込み中…