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

HRID 55579

반응식

HRID 55579 반응식
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

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 702Ethanol용매2회HCID 6228Dimethylformamide용매HCID 6342Acetonitrile용매

반응 조건

온도
100 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-5e754eca2d24419299855597546ce293
출처 데이터셋
uspto-grants-1997_04
특허 번호
US05624927

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