반응 #2271679

ord-b7f5ae86b09e4710a0e64cd9338851c2

반응 방정식

O=C(O)/C=C/C(=O)O
fumaric acid
Cl.Fc1ccc2c(C3CCNCC3)noc2c1
6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride
O=C([O-])[O-].[K+].[K+]
K2CO3
CC(=O)c1ccc(OCCCBr)c(C)c1
1-[4-(3-bromopropoxy)-3-methylphenyl]ethanone
CC(=O)c1ccc(OCCCN2CCC(c3noc4cc(F)ccc34)CC2)c(C)c1.CC(=O)c1ccc(OCCCN2CCC(c3noc4cc(F)ccc34)CC2)c(C)c1.O=C(O)/C=C/C(=O)O
1-[4-[3-[4-(6-fluoro-1,2-benzisoxazole-3-yl)-1-piperidinyl]propoxy]-3-methylpheny]ethanone hemifumarate

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타At the end of the reaction
  2. 2
    농축the solvent was concentrated down to about 30 ml
  3. 3
    기타partitioned between water (200 ml) and dichloromethane (300 ml)
  4. 4
    기타The dichloromethane solution was separated
  5. 5
    세척washed with water and brine
  6. 6
    건조dried over MgSO4
  7. 7
    기타The crude product from the evaporated solution was purified by flash chromatography over a silica gel column (SiO2, 60 g, eluted with 1% methanol in dichloromethane, 600 ml; 2% methanol in dichloromethane, 600 ml)
  8. 8
    기타The material thus obtained

실험 절차

A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride (3.0 g; 11.7 mmol). K2CO3 (3.0g), and 1-[4-(3-bromopropoxy)-3-methylphenyl]ethanone (3.19 g) in dimethylformamide (20 ml) and acetonitrile (50 ml) was heated at 95° C. for 4 hours. At the end of the reaction, the solvent was concentrated down to about 30 ml, then partitioned between water (200 ml) and dichloromethane (300 ml). The dichloromethane solution was separated and washed with water and brine, then dried over MgSO4. The crude product from the evaporated solution was purified by flash chromatography over a silica gel column (SiO2, 60 g, eluted with 1% methanol in dichloromethane, 600 ml; 2% methanol in dichloromethane, 600 ml). The material thus obtained was a light yellow oil, weight: 2.07 g (43%). This oil was dissolved in ethanol and treated with a solution of fumaric acid (585 mg) in ethanol. The 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazole-3-yl)-1-piperidinyl]propoxy]-3-methylpheny]ethanone hemifumarate crystals formed on cooling at 0° C. This was collected and weighed 1.5 g., m.p.=185°-187° C.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: USRE037729E1uspto-grants-2002_06