Potassium Carbonate → N-[3-[3-[4(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-4-methoxyphenyl]acetamide hemifumarate

HRID 55579

反応式

HRID 55579 の反応式
Cl.[F:2][C:3]1[CH:17]=[CH:16][C:6]2[C:7]([CH:10]3[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]3)=[N:8][O:9][C:5]=2[CH:4]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:25][CH2:26][CH2:27][O:28][C:29]1[CH:30]=[C:31]([NH:37][C:38](=[O:40])[CH3:39])[CH:32]=[CH:33][C:34]=1[O:35][CH3:36].[C:41]([OH:48])(=[O:47])/[CH:42]=[CH:43]/[C:44]([OH:46])=[O:45]>CN(C)C=O.C(#N)C.C(O)C>[C:41]([OH:48])(=[O:47])/[CH:42]=[CH:43]/[C:44]([OH:46])=[O:45].[F:2][C:3]1[CH:17]=[CH:16][C:6]2[C:7]([CH:10]3[CH2:11][CH2:12][N:13]([CH2:25][CH2:26][CH2:27][O:28][C:29]4[CH:30]=[C:31]([NH:37][C:38](=[O:40])[CH3:39])[CH:32]=[CH:33][C:34]=4[O:35][CH3:36])[CH2:14][CH2:15]3)=[N:8][O:9][C:5]=2[CH:4]=1.[F:2][C:3]1[CH:17]=[CH:16][C:6]2[C:7]([CH:10]3[CH2:11][CH2:12][N:13]([CH2:25][CH2:26][CH2:27][O:28][C:29]4[CH:30]=[C:31]([NH:37][C:38](=[O:40])[CH3:39])[CH:32]=[CH:33][C:34]=4[O:35][CH3:36])[CH2:14][CH2:15]3)=[N:8][O:9][C:5]=2[CH:4]=1

参加物

8

反応物 4

HCID 11430Potassium CarbonateHCID 444972Fumaric AcidHCID 11334359R-56109 hydrochlorideHCID 21960090N-[3-(bromopropoxy)-4-methoxyphenyl]acetamide

生成物 1

HCID 131718778N-[3-[3-[4(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-4-methoxyphenyl]acetamide hemifumarate

試薬・触媒・溶媒 3

HCID 702Ethanol溶媒2 回HCID 6228Dimethylformamide溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
100 °C

実験手順

A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride (3.94 g, 15.4 mmol), K2CO3 (3.67 g, 26.6 mmole), N-[3-(3-bromopropoxy)-4-methoxyphenyl]acetamide (5.56 g, 18.6 mmol) in dimethylformamide (75 ml) and acetonitrile (100 ml) was heated at 100° C. for 3 hours. At the end of the reaction, the solvent was concentrated and the mixture was extracted into dichloromethane (500 ml). The organic solution was washed with water (500 ml) and brine (400 ml), dried, then concentrated to a crude oil. The purification was effected by flash chromatography over a silica gel column (SiO2, 65 g, eluted with 1% CH3OH:dichloromethane, 1.2 l; and 3% CH3OH:dichloromethane, 500 ml). The material thus obtained weighed 2.33 g (34.3%) as an oil. This material was dissolved in ethanol and treated with a solution of fumaric acid (661 mg) in ethanol. The N-[3-[3-[4-(6-fluoro-1,2 benzisoxazol-3-yl)-1-piperidinyl]propoxy]-4-methoxyphenyl]acetamide hemifumarate was obtained as off-white crystals weighing 2.17 g, m.p.=205°-206° C.

後処理

  1. customAt the end of the reaction
  2. concentrationthe solvent was concentrated
  3. extractionthe mixture was extracted into dichloromethane (500 ml)
  4. washThe organic solution was washed with water (500 ml) and brine (400 ml)
  5. customdried
  6. concentrationconcentrated to a crude oil
  7. customThe purification
  8. washwas effected by flash chromatography over a silica gel column (SiO2, 65 g, eluted with 1% CH3OH:dichloromethane, 1.2 l; and 3% CH3OH:dichloromethane, 500 ml)
  9. customThe material thus obtained

出典と根拠

ORDレコード
ord-5e754eca2d24419299855597546ce293
出典データセット
uspto-grants-1997_04
特許番号
US05624927

関連ノート

読み込み中…