Sodium Bicarbonate → 1-[4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]2-hydroxy-5-methoxyphenyl]ethanone

HRID 357433ノート

反応式

HRID 357433 の反応式
[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.Cl[CH2:18][CH2:19][CH2:20][O:21][C:22]1[C:27]([O:28][CH3:29])=[CH:26][C:25]([C:30](=[O:32])[CH3:31])=[C:24]([OH:33])[CH:23]=1.C([O-])(O)=O.[Na+]>C(#N)C>[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:10][CH2:11][N:12]([CH2:18][CH2:19][CH2:20][O:21][C:22]4[C:27]([O:28][CH3:29])=[CH:26][C:25]([C:30](=[O:32])[CH3:31])=[C:24]([OH:33])[CH:23]=4)[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

参加物

5

反応物 3

HCID 516892Sodium BicarbonateHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazoleHCID 184672431-[4-(3-Chloropropoxy)-2-hydroxy-5-methoxyphenyl]ethanone

生成物 1

HCID 224570921-[4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]2-hydroxy-5-methoxyphenyl]ethanone収率 13.1%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (4.2 g, 19 mmol), 1-[4-(3-chloropropoxy)-2-hydroxy-5-methoxyphenyl]ethanone (5.0 g, 19 mmol), NaHCO3 (1.8 g, 20 mmol) and acetonitrile (120 mL) was stirred and refluxed for 16 hours. The reaction was filtered and the filtrate was concentrated to a dark oil. The oil was taken up in anhydrous ether and ethereal HCl was added to precipitate 8.7 g of an off-white hydrochloride salt. A 2.0 g sample of the salt was converted to its free base and chromatographed by preparative HPLC (silica gel with 5% MeOH/CH2 Cl2 as eluent). Concentration of the desired fractions gave 1.1 g of a white solid, which was recrystallized from EtOH to yield 0.85 g of the product, m.p. 122°-124° C.

後処理

  1. temperaturerefluxed for 16 hours
  2. filtrationThe reaction was filtered
  3. concentrationthe filtrate was concentrated to a dark oil
  4. additionethereal HCl was added
  5. customto precipitate 8.7 g of an off-white hydrochloride salt
  6. customchromatographed by preparative HPLC (silica gel with 5% MeOH/CH2 Cl2 as eluent)

出典と根拠

ORDレコード
ord-3d85eefac8d846a29a3ab2d38bd0c1fb
出典データセット
uspto-grants-1998_11
特許番号
US05840727

反応ノート

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