Methyl iodide → n-Methyl-hydroxybenzoquinoline

HRID 896758

반응식

HRID 896758 반응식
[N:1]1[C:10]2C(=[CH:6][CH:7]=[C:8]3[CH:14]=[CH:13][CH:12]=[CH:11][C:9]3=2)C=C[CH:2]=1.CI.C[O:18]C1C=NC2C(C=1)=CC=C1C=CC=CC=21.[CH2:33]([Li])[CH2:34][CH2:35][CH3:36].[NH4+].[Cl-]>C1COCC1.CCOC(C)=O>[CH3:2][N:1]1[C:10]2[C:36](=[CH:6][CH:7]=[C:8]3[CH:14]=[CH:13][CH:12]=[CH:11][C:9]3=2)[CH:35]=[CH:34][CH:33]1[OH:18]

참가 물질

8

반응물 5

HCID 6328Methyl iodide2회HCID 9191Benzo(h)quinolineHCID 25517Ammonium ChlorideHCID 111951503-MethoxybenzoquinolineHCID 178418339Butyllithium

생성물 1

HCID 67021686n-Methyl-hydroxybenzoquinoline

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

Compound 13 was alkylated with MeI according to a general amino group alkylation procedure as follows. The 3-methoxybenzoquinoline derivative (100 mg) 13 was suspended in 5 mL of dry THF and cooled to −5° C. (ice/NaCl). 1.1 equivalents of n-butyl lithium (1 M) was added dropwise, and the reaction was stirred for 1 hour. 3 equivalents of the MeI alkylating agent was added slowly and the reaction was allowed to stir at room temperature for 2 hours. Aqueous work-up using NH4Cl and EtOAc gave a crude alkylated 3-methoxybenzoquinoline intermediate 14. Intermediate 14 was then purified by normal phase flash chromatography employing EtOAc:hexane (1:19) as the mobile phase (1HNMR: CD3Cl d 8.1 (broad d, 1 H, J=8.1 Hz), 7.68(dd, 1 H, J=8.1, 1.8 Hz), 7.34 (m, 2 H), 6.8 (s, 1 H), 3.92 (s, 3 H), 3.21 (m, 2 H), 2.94 (s, 3 H), 2.77 (t, 2 H, J=6.6 Hz), 1.92 (m, 2 H)). Subsequent methoxy group deprotection by the general boron tribromide procedure described above in Example 1 resulted in the N-methyl-hydroxybenzoquinoline derivative 15.

후처리

  1. stirringto stir at room temperature for 2 hours
  2. customgave a crude alkylated 3-methoxybenzoquinoline intermediate 14
  3. customIntermediate 14 was then purified by normal phase flash chromatography

출처 및 근거

ORD 기록
ord-41b4f38a505b4be0a28c9634130f94d3
출처 데이터셋
uspto-grants-2005_07
특허 번호
US06919445B2

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