Diethyl Ether → 1-(4-Bromo-2-(methoxymethyl)phenyl)-2-methylpiperidine

HRID 2410476

반응식

HRID 2410476 반응식
CS(Cl)(=O)=O.[Br:6][C:7]1[CH:8]=[CH:9][C:10]([N:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH:16]2[CH3:21])=[C:11]([CH2:13][OH:14])[CH:12]=1.[CH3:22]CN(C(C)C)C(C)C.CCOCC>C(Cl)Cl.CO>[Br:6][C:7]1[CH:8]=[CH:9][C:10]([N:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH:16]2[CH3:21])=[C:11]([CH2:13][O:14][CH3:22])[CH:12]=1

참가 물질

7

반응물 4

HCID 3283Diethyl EtherHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 58554197(5-Bromo-2-(2-methylpiperidin-1-YL)phenyl)methanol

생성물 1

HCID 585541231-(4-Bromo-2-(methoxymethyl)phenyl)-2-methylpiperidine수율 92.2%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6344Dichloromethane용매

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온도
0 °C

실험 절차

Methanesulfonyl chloride (4.0 mL, 51.6 mmol) was added into a solution of [5-bromo-2-(2-methylpiperidin-1-yl)phenyl]methanol (13.43 g, 47.3 mmol) and DIEA (17.7 mL, 104 mmol) in anhydrous DCM (130 mL) cooled at 0° C. After 1 hour, the reaction mixture was diluted with MeOH (150 mL) and heated at 50° C. for 3 hours. The solvents were removed under reduced pressure to give a brown oil. The residue was taken up with Et2O (450 mL), and then washed with water (150 mL, pH 8 adjusted with a 5N aqueous solution of NaOH), saturated aqueous solution of NH4Cl (2×150 mL) and brine (150 mL). The aqueous layers were extracted with Et2O (150 mL). The combined organic layers were dried (MgSO4) and the solvent was removed under reduced pressure to give the title compound as a brown yellow oil (13.0 g, 92%) used without further purification in the next step. HPLC (Method A), Rt 2.9 min (Purity: 97.1%). HPLC/MS, M+(ESI): 298.1, 300.1. 1H NMR (CDCl3, 300 MHz) δ 7.59 (d, J=2.5 Hz, 1H), 7.36 (dd, J=8.5, 2.5 Hz, 1H), 7.03 (d, J=8.5 Hz, 1H), 4.60 (d, J=12.8 Hz, 1H), 4.52 (d, J=12.8 Hz, 1H), 3.44 (s, 3H), 2.96-2.81 (m, 2H), 2.51 (m, 1H), 1.77 (m, 2H), 1.64 (m, 2H), 1.50-1.30 (m, 2H), 0.79 (d, J=6.1 Hz, 3H).

후처리

  1. temperatureheated at 50° C. for 3 hours
  2. customThe solvents were removed under reduced pressure
  3. customto give a brown oil
  4. washwashed with water (150 mL, pH 8
  5. extractionThe aqueous layers were extracted with Et2O (150 mL)
  6. dry with materialThe combined organic layers were dried (MgSO4)
  7. customthe solvent was removed under reduced pressure

출처 및 근거

ORD 기록
ord-85a616fe63f946ea924b66aba65de616
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08815919B2

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