Iodine → Ethyl 3-(3,4-dichlorophenyl)-1-methylpiperidine-4-carboxylate

HRID 1260906노트

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HRID 1260906 반응식
[Mg].II.[Cl:4][C:5]1[CH:6]=[C:7](Br)[CH:8]=[CH:9][C:10]=1[Cl:11].ClC1C=C(Br)C=CC=1Cl.C(OCC)C.[CH3:27][N:28]1[CH2:33][CH:32]=[C:31]([C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH2:30][CH2:29]1>C(OCC)C.[Cu]I.O>[Cl:4][C:5]1[CH:6]=[C:7]([CH:32]2[CH:31]([C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH2:30][CH2:29][N:28]([CH3:27])[CH2:33]2)[CH:8]=[CH:9][C:10]=1[Cl:11]

참가 물질

9

반응물 5

HCID 807IodineHCID 290134-Bromo-1,2-dichlorobenzeneHCID 566021Ethyl 1-methyl-1,2,3,6-tetrahydro-4-pyridinecarboxylateHCID 5462224MagnesiumHCID 672334723,4-Dichlorobromobenzene diethyl ether

생성물 1

HCID 67231835Ethyl 3-(3,4-dichlorophenyl)-1-methylpiperidine-4-carboxylate수율 71.9%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 962Water용매HCID 3283Diethyl Ether용매3회

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온도
37.5 °C

실험 절차

To a suspension of magnesium (10.76 g) in diethyl ether (110 mL) was added a trace amount of iodine. About one-tenth of a solution of 3,4-dichlorobromobenzene (100 g) in diethyl ether (110 mL) was added slowly at 35-40° C., and the mixture was vigorously stirred until the reaction started. When the reaction started, the rest of the 3,4-dichlorobromobenzene/diethyl ether solution was added slowly while cooling the reaction mixture to 35-40° C. When all was added, the mixture was stirred at 40° C. for 1 hr, and then cooled to 0° C. To the reaction mixture was added copper(I) iodide (12.6 g), and the compound (56.2 g) obtained in step 1 was slowly added dropwise at 0° C. The reaction mixture was stirred at 0° C. for 1 hr, and at room temperature for 1 hr. The reaction mixture was poured into water (40 mL), diethyl ether (500 mL) was added, and the precipitate was removed by decantation. The reaction mixture was washed with aqueous ammonium chloride solution and brine and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 20% ethyl acetate/hexane→2.5% aqueous ammonia/17.5% methanol/ethyl acetate) to give crude ethyl 3-(3,4-dichlorophenyl)-1-methylpiperidine-4-carboxylate (cis/trans mixture) (75.5 g) as a brown oil.

후처리

  1. additionWhen all was added
  2. stirringthe mixture was stirred at 40° C. for 1 hr
  3. temperaturecooled to 0° C
  4. stirringThe reaction mixture was stirred at 0° C. for 1 hr
  5. additionwas added
  6. customthe precipitate was removed by decantation
  7. washThe reaction mixture was washed with aqueous ammonium chloride solution and brine
  8. customdried
  9. customthe solvent was evaporated under reduced pressure
  10. customThe obtained residue was purified by silica gel column chromatography (solvent gradient; 20% ethyl acetate/hexane→2.5% aqueous ammonia/17.5% methanol/ethyl acetate)

출처 및 근거

ORD 기록
ord-02069762a3954bb8a80f7578f85e7431
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08470816B2

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