Potassium Carbonate → 3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)1-piperidinyl]-2,2-dimethyl1-propanol fumarate

HRID 235442

反応式

HRID 235442 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.[C:17]([O-:20])([O-:19])=O.[K+].[K+].Br[CH2:24][C:25]([CH3:29])([CH3:28])[CH2:26][OH:27]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.O.C(#N)C>[C:4]([OH:27])(=[O:8])/[CH:5]=[CH:15]/[C:17]([OH:20])=[O:19].[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:10][CH2:11][N:12]([CH2:24][C:25]([CH3:29])([CH3:28])[CH2:26][OH:27])[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

参加物

7

反応物 3

HCID 11430Potassium CarbonateHCID 1425013-Bromo-2,2-dimethyl-1-propanolHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazole

生成物 1

HCID 219600703-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)1-piperidinyl]-2,2-dimethyl1-propanol fumarate

試薬・触媒・溶媒 3

HCID 94433Tetrabutylammonium hydrogen sulfate触媒HCID 962Water溶媒HCID 6342Acetonitrile溶媒

実験手順

A mixture of 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (3.0 g, 13.6 mmol), K2CO3 (12.5 g, 17.5 mmol), 3-bromo-2,2-dimethyl-1-propanol (3 g, 21 mmol, 1.5 eq. tetra-butylammonium hydrogen sulfate (1 g, phase transfer catalyst) in water (5 ml) and acetonitrile (150 ml) was heated at reflux for 43 days. TLC showed a small spot for the expected product. The mixture was diluted with EtOAc (400 ml) and washed with brine. The organic solution was dried and concentrated to a dark brown mixture. The crude mixture was purified carefully by flash chromatography (SiO2, 95 g to afford the dried pure product; 260 mg, (6%) as an oil. This oil was converted to the fumarate salt by treatment with fumaric acid (98.5 mg, 1.0 eq.) in ethanol. Recrystallization from ethanol:ether yielded 210 mg of white crystals, m.p.=144°-145° C.

後処理

  1. temperaturewas heated
  2. temperatureat reflux for 43 days

出典と根拠

ORDレコード
ord-23f7ee93333b4eb9aaaa4718743b7b1e
出典データセット
uspto-grants-1997_01
特許番号
US05597842

関連ノート

読み込み中…