Water → 1'-benzyl-5-chloro-3H-spiro[isobenzofuran-1,4'-piperidin]-3-one

HRID 270091

反応式

HRID 270091 の反応式
Br[C:2]1[CH:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].C([Li])CCC.[CH2:17]([N:24]1[CH2:29][CH2:28][C:27](=O)[CH2:26][CH2:25]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.O>O1CCCC1.CCCCCC.C(OCC)C>[CH2:17]([N:24]1[CH2:29][CH2:28][C:27]2([C:2]3[CH:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:3]=3[C:4](=[O:5])[O:6]2)[CH2:26][CH2:25]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

参加物

8

反応物 4

HCID 962WaterHCID 192201-Benzyl-4-piperidoneHCID 890272-Bromo-5-chlorobenzoic acidHCID 178418339Butyllithium

生成物 1

HCID 598336431'-benzyl-5-chloro-3H-spiro[isobenzofuran-1,4'-piperidin]-3-one収率 37.2%

試薬・触媒・溶媒 3

HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8058Hexane溶媒

反応条件

温度
-78 °C

実験手順

To a solution of 2-bromo-5-chlorobenzoic acid (2.35 g, 10.0 mmol) in tetrahydrofuran (THF) (15 mL) was added, a 1.6 M solution in hexane, n-butyllithium (20 mL, 32.0 mmol) slowly at −78° C. under nitrogen. After addition was complete the reaction mixture was kept on stirring at −78° C. for 3 h. Then a solution of 1-benzylpiperidin-4-one (3.78 g, 20.0 mmol) in THF (10 mL) was added slowly to the reaction mixture at −78° C. After addition was complete the reaction temperature was raised to room temperature and the reaction mixture was kept on stirring at room temperature overnight. The reaction mixture was poured into a mixture of water (60 mL) and diethyl ether (60 mL), layers were separated. The aqueous layer was extracted with diethyl ether (2×20 mL). The aqueous layer was acidified with aqueous 6M hydrochloric acid (HCl) to pH 2 and boiled for 1 h, cooled to 0° C., pH was adjusted to 10.0 by addition of aqueous sodium hydroxide (NaOH) (6M) and rapidly extracted with trichloromethane (CHCl3). The organic layer was washed with water, dried over sodium sulphate (Na2SO4), filtered and concentrated in vacuo to give the subtitled compound (1.22 g) and it was pure enough for the next step.

後処理

  1. customslowly at −78° C.
  2. additionAfter addition
  3. additionAfter addition
  4. temperaturewas raised to room temperature
  5. stirringon stirring at room temperature overnight
  6. customwere separated
  7. extractionThe aqueous layer was extracted with diethyl ether (2×20 mL)
  8. waitboiled for 1 h
  9. temperaturecooled to 0° C.
  10. additionpH was adjusted to 10.0 by addition of aqueous sodium hydroxide (NaOH) (6M)
  11. extractionrapidly extracted with trichloromethane (CHCl3)
  12. washThe organic layer was washed with water
  13. dry with materialdried over sodium sulphate (Na2SO4)
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-c939a2f578e8451881a916358a2d0398
出典データセット
uspto-grants-2008_11
特許番号
US07449475B2

関連ノート

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