4-Bromoanisole → 1-(3-Bromophenyl)-1-(4-methoxyphenyl)-1H-isoindol-3-amine

HRID 2264726노트

반응식

HRID 2264726 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.C([Li])CCC.[Br:15][C:16]1[CH:17]=[C:18]([C:22]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[C:36]#[N:37])=[N:23]S(C(C)(C)C)=O)[CH:19]=[CH:20][CH:21]=1>O1CCCC1>[Br:15][C:16]1[CH:17]=[C:18]([C:22]2([C:2]3[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=3)[C:30]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[C:36]([NH2:37])=[N:23]2)[CH:19]=[CH:20][CH:21]=1

참가 물질

5

반응물 3

HCID 77304-BromoanisoleHCID 72335434N-[(3-bromophenyl)(2-cyanophenyl)methylene]-2-methylpropane-2-sulfinamideHCID 178418339Butyllithium

생성물 1

HCID 248749461-(3-Bromophenyl)-1-(4-methoxyphenyl)-1H-isoindol-3-amine수율 59.3%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-78 °C

실험 절차

To a −78° C. solution of 4-bromoanisole (0.45 mL, 3.6 mmol) in tetrahydrofuran (15 mL) was n-butyllithium (2.5 M in hexane, 1.3 mL, 3.3 mmol) added, after 0.5 h a solution of N-[(3-bromophenyl)(2-cyanophenyl)methylene]-2-methylpropane-2-sulfinamide (Scheme #5, N) (1.2 g, 3.0 mmol) in tetrahydrofuran (5 mL) was added. The reaction mixture was stirred at −78° C. for 3 h and then quenched by addition of water. Ethyl acetate was added and the mixture was washed with water and brine, dried over magnesium sulfate and concentrated. The residue was dissolved in methanol (25 mL) and treated with hydrochloric acid (2 M in diethyl ether, 3.0 mL, 6.0 mml) over night. The reaction mixture was concentrated and then partitioned between aqueous saturated sodium bicarbonate and chloroform, the organic phase was dried over magnesium sulfate and concentrated. Purification by column chromatography using a gradient of methanol in dichloromethane gave the title compound (0.70 g, 59%). 1H NMR (CDCl3) δ 7.57-7.48 (m, 3 H), 7.47-7.41 (m, 1 H), 7.39-7.32 (m, 2 H), 7.32-7.28 (m, 1 H), 7.26-7.20 (m, 2 H), 7.10 (t, J=7.83 Hz, 1 H), 6.83-6.77 (m, 2 H), 5.86 (br s, 2 H), 3.75 (s, 3 H); MS (AP) m/z 393, 395 [M+1]+.

후처리

  1. customTo a −78° C.
  2. additionwas added
  3. customquenched by addition of water
  4. additionEthyl acetate was added
  5. washthe mixture was washed with water and brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in methanol (25 mL)
  9. additiontreated with hydrochloric acid (2 M in diethyl ether, 3.0 mL, 6.0 mml) over night
  10. concentrationThe reaction mixture was concentrated
  11. custompartitioned between aqueous saturated sodium bicarbonate and chloroform
  12. dry with materialthe organic phase was dried over magnesium sulfate
  13. concentrationconcentrated
  14. customPurification by column chromatography

출처 및 근거

ORD 기록
ord-24e93e1db6324c279564bd6ea03dd634
출처 데이터셋
uspto-grants-2010_12
특허 번호
US07855213B2

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