Hydrochloric Acid → HCID 18793463、化合物

HRID 406480ノート

反応式

HRID 406480 の反応式
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=1.[CH2:14]([N:21]1[CH2:26][CH2:25][C:24](=[O:27])[CH:23]([CH3:28])[CH2:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.Cl.[NH4+].[OH-]>CCCCCC.CCOCC>[CH2:14]([N:21]1[CH2:26][CH2:25][C:24]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)([OH:27])[CH:23]([CH3:28])[CH2:22]1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 99931-Bromo-4-fluorobenzeneHCID 14923Ammonium HydroxideHCID 5609651-Benzyl-3-methyl-4-piperidoneHCID 178418339Butyllithium

生成物 1

HCID 18793463HCID 18793463、化合物収率 84.2%

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒4 回HCID 8058Hexane溶媒

反応条件

温度
-50 °C

実験手順

To a solution of n-butyllithium (1-2 equivalents, preferably 1.1 equivalents) (1.6 M in hexane, 8.6 ml, 13.76 mmol) in Et2O (10.32 mL) was added a solution of 1-bromo-4-fluorobenzene (2.21 g, 12.63 mmol) in Et2O (5 ml) at about −50° C. After the reaction mixture was stirred at about −50° C. for about 40 min, a solution of 1-benzyl-3-methylpiperidin-4-one (2.00 g, 9.84 mmol) in Et2O (7 mL) was added dropwise. The mixture was allowed to warm up to about −20° C. to 0° C. (preferably −10° C.). 1M hydrochloric acid (20 mL) was added and the organic phase was discarded. Et2O (20 mL) was added to the aqueous solution and aqueous NH4OH was added to the solution until pH>9. The organic layer was separated and the aqueous layer was extracted with DCM (20 mL), The combined organic portions were washed with brine (2×10 mL), dried over MgSO4, filtered, and concentrated in vacuo to give 1-benzyl-4-(4-fluorophenyl)-3-methylpiperidin-4-ol (2.48 g, 84%) as an oil which was used in subsequent reactions without further purification. RP-HPLC (Table 1, Method a) Rt 1.63 min; m/z: (M+H)+ 300.

後処理

  1. temperatureto warm up to about −20° C. to 0° C. (preferably −10° C.)
  2. additionwas added to the solution until pH>9
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with DCM (20 mL)
  5. washThe combined organic portions were washed with brine (2×10 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-95345ab315f14d0281bad4e14488c3e8
出典データセット
uspto-grants-2014_06
特許番号
US08754107B2

反応ノート

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