Hydrochloric Acid → 3-(3-i-Propoxyphenyl)-1,3-dimethyl-4-hydroxypiperidine

HRID 467267

反応式

HRID 467267 の反応式
Br[C:2]1[CH:3]=[C:4]([O:8][CH:9]([CH3:11])[CH3:10])[CH:5]=[CH:6][CH:7]=1.C([Li])CCC.[CH3:17][N:18]1[CH2:23][CH2:22][C:21](=[O:24])[CH:20]([CH3:25])[CH2:19]1.Cl>C1COCC1>[CH:9]([O:8][C:4]1[CH:3]=[C:2]([C:20]2([CH3:25])[CH:21]([OH:24])[CH2:22][CH2:23][N:18]([CH3:17])[CH2:19]2)[CH:7]=[CH:6][CH:5]=1)([CH3:11])[CH3:10]

参加物

6

反応物 4

HCID 313Hydrochloric Acid2 回HCID 1073111,3-Dimethyl-4-piperidoneHCID 32608011-Bromo-3-isopropoxybenzeneHCID 178418339Butyllithium

生成物 1

HCID 197358933-(3-i-Propoxyphenyl)-1,3-dimethyl-4-hydroxypiperidine収率 662.3%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-70 °C

実験手順

The 3-bromo-i-propoxybenzene (200 g, 0.08703 mol) was combined with THF (540 ml) under nitrogen and cooled to about -75° C. n-Butyl lithium (565 ml, 0.8306 mol) was added dropwise while maintaining the mixture at less than -70° C. After 2 hours 1,3-Dimethyl-4-piperidone (106.7 g, 0.8389 mol) was added while maintaining the temperature of the mixture between -80° C. and -70° C. After stirring 2 hours at -70° C., the reaction mixture was then added to 6N HCl (280 ml) while maintaining the temperature at 20°-25° C. The pH was adjusted to 1 with 12 N HCl. The aqueous layer containing product was separated and heptane (320 ml) was added along with 50% NaOH (48 ml, pH=13-14) and the resulting mixture allowed to stand overnight. The mixture was heated to 45° -50° C. and the upper layer was separated. The remaining aqueous layer was extracted with heptane (320 ml) at 45°-50° C. The combined organic fractions were washed with de-ionized water (120 ml) at 45°-50° C. The resulting organic layer was vacuum distilled at a pot temperature of about 55° C. at 100 mmHg. Crystallization from heptane and drying provided 151.8 g of 3-(3-i-propoxyphenyl)-1,3-dimethyl-4-hydroxypiperidine. Melting point 75.0°-76.0° C.

後処理

  1. additionwas added dropwise
  2. temperaturewhile maintaining the mixture at less than -70° C
  3. temperaturewhile maintaining the temperature of the mixture between -80° C. and -70° C
  4. temperaturewhile maintaining the temperature at 20°-25° C
  5. additionThe aqueous layer containing product
  6. customwas separated
  7. additionheptane (320 ml) was added along with 50% NaOH (48 ml, pH=13-14)
  8. waitto stand overnight
  9. temperatureThe mixture was heated to 45° -50° C.
  10. customthe upper layer was separated
  11. extractionThe remaining aqueous layer was extracted with heptane (320 ml) at 45°-50° C
  12. washThe combined organic fractions were washed with de-ionized water (120 ml) at 45°-50° C
  13. distillationdistilled at a pot temperature of about 55° C. at 100 mmHg
  14. customCrystallization from heptane
  15. customdrying

出典と根拠

ORDレコード
ord-8fdd9c4695c644eeaa7d7f851fcf6135
出典データセット
uspto-grants-1992_10
特許番号
US05159081

関連ノート

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