Trifluoroacetic acid → 2-[4-(2-Diisopropylamino-ethoxy)-3-methoxy-phenyl]-2,3-dihydro-isoindol-1-one

HRID 1353064ノート

反応式

HRID 1353064 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=O)[N:6]([C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][N:21]([CH:25]([CH3:27])[CH3:26])[CH:22]([CH3:24])[CH3:23])=[C:14]([O:28][CH3:29])[CH:13]=1)[C:5]2=[O:30].[BH4-].[Na+].C(N(C(C)C)CCOC1C=CC(N2C(O)C3C(=CC=CC=3)C2=O)=CC=1OC)(C)C.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C1COCC1.C(O)(=O)C.ClCCl.C(O)(C)C>[CH:25]([N:21]([CH:22]([CH3:24])[CH3:23])[CH2:20][CH2:19][O:18][C:15]1[CH:16]=[CH:17][C:12]([N:6]2[CH2:7][C:8]3[C:4](=[CH:3][CH:2]=[CH:10][CH:9]=3)[C:5]2=[O:30])=[CH:13][C:14]=1[O:28][CH3:29])([CH3:26])[CH3:27]

参加物

10

反応物 5

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 4311764Sodium borohydrideHCID 179893652-[4-(2-Diisopropylamino-ethoxy)-3-methoxy-phenyl]-3-hydroxy-2,3-dihydro-isoindol-1-oneHCID 17989375HCID 17989375、化合物

生成物 1

HCID 179893332-[4-(2-Diisopropylamino-ethoxy)-3-methoxy-phenyl]-2,3-dihydro-isoindol-1-one

試薬・触媒・溶媒 4

HCID 176Acetic Acid触媒HCID 3776Isopropanol溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

A solution of 5-bromo-2-[4-(2-diisopropylamino-ethoxy)-3-methoxy-phenyl]-isoindole-1,3-dione [Example A1] (66 mg, 0.14 mmol) was dissolved in THF (ml) and treated with sodium borohydride (5.2 mg, 0.14 mmol). After stirring for 2 hours, the mixture was treated with isopropanol, stirred for a further 1 h then treated with acetic acid (2 drops) and stirred for 16 h at RT. The solvent was removed and the residue purified by flash chromatography to give an approximately 1:1 mixture of the 5- and 6-bromo substituted isomers of 2-[4-(2-diisopropylamino-ethoxy)-3-methoxy-phenyl]-3-hydroxy-2,3-dihydro-isoindol-1-one (37 mg). This material was dissolved in dichloromethane (2 ml) and treated with triethylsilane (1 ml) and trifluoroacetic acid (0.5 ml). The mixture was stirred at RT for 16 hours, the solvents were removed in vacuo and the residue purified by flash chromatography on silica gel (eluting with methanol-dichloromethane-aq. ammonia) to obtain 2-[4-(2-diisopropylamino-ethoxy)-3-methoxy-phenyl]-2,3-dihydro-isoindol-1-one as an approximately 1:1 mixture of 5- and 6-bromo isomers (33 mg). A solution of this material in benzene (5 ml) was treated with aqueous sodium carbonate (2M, 1 ml), ethanol (1 ml), phenylboronic acid (9 mg, 0.07 mmol) and tetrakis(triphenylphosphine)palladium[0] (10 mg) and the mixture heated to reflux for 16 h. The less dense phase was decanted, filtered through filter-aid (washing with dichloromethane), the filtrate evaporated and purified by flash chromatography on silica gel (eluting with dichloromethane-methanol-aq. ammonia) and reverse phase preparative chromatography (aq. MeCN, TFA) to give the title compounds as an approximately 1:1 mixture of isomers as their TFA salts;

後処理

  1. stirringstirred for a further 1 h
  2. stirringstirred for 16 h at RT
  3. customThe solvent was removed
  4. customthe residue purified by flash chromatography
  5. customto give
  6. stirringThe mixture was stirred at RT for 16 hours
  7. customthe solvents were removed in vacuo
  8. customthe residue purified by flash chromatography on silica gel (eluting with methanol-dichloromethane-aq. ammonia)

出典と根拠

ORDレコード
ord-ff0b98be29de41549ab7f2356b6d6f51
出典データセット
uspto-grants-2007_05
特許番号
US07220777B2

反応ノート

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