تفاعل #2271679

ord-b7f5ae86b09e4710a0e64cd9338851c2

معادلة التفاعل

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

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    أخرىAt the end of the reaction
  2. 2
    تركيزthe solvent was concentrated down to about 30 ml
  3. 3
    أخرىpartitioned between water (200 ml) and dichloromethane (300 ml)
  4. 4
    أخرىThe dichloromethane solution was separated
  5. 5
    غسيلwashed with water and brine
  6. 6
    تجفيفdried over MgSO4
  7. 7
    أخرىThe 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
    أخرىThe material thus obtained

الإجراء التجريبي

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.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: USRE037729E1uspto-grants-2002_06