1,2-Dichloroethane → (2-bromo-1-methyl-1H-imidazole-5-yl)(pyrrolidin-1-yl)methanone

HRID 1716865노트

반응식

HRID 1716865 반응식
[Br:1][C:2]1[N:3]([CH3:10])[C:4]([C:7]([OH:9])=O)=[CH:5][N:6]=1.C(Cl)CCl.[CH:15]1[CH:16]=CC2N(O)N=[N:21][C:19]=2[CH:20]=1.N1CCCC1>O1CCCC1>[Br:1][C:2]1[N:3]([CH3:10])[C:4]([C:7]([N:21]2[CH2:16][CH2:15][CH2:20][CH2:19]2)=[O:9])=[CH:5][N:6]=1

참가 물질

6

반응물 4

HCID 111,2-DichloroethaneHCID 31268PyrrolidineHCID 757711-HydroxybenzotriazoleHCID 510638092-bromo-1-methyl-1H-imidazole-5-carboxylic acid

생성물 1

HCID 57550233(2-bromo-1-methyl-1H-imidazole-5-yl)(pyrrolidin-1-yl)methanone수율 95%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

To a suspension of methyl 2-bromo-1-methyl-1H-imidazole-5-carboxylate (2.18 g, 10 mmol) in tetrahydrofuran (60 mL) and water (6 mL) was added lithium hydroxide (0.72 mg, 30 mmol) and the reaction mixture was allowed to stir at room temperature for 2.5 h. The solvent was removed under reduced pressure and water was added followed by formic acid, the resulting precipitate was filtered, washed with water and dried under vacuum overnight to afford the 2-bromo-1-methyl-1H-imidazole-5-carboxylic acid (82%). 1H-NMR (300 MHz, CDCl3): 7.79 (s, 1H), 3.91 (s, 3H). LCMS (ESI+) 205.0 (MH+). To a solution of the carboxylic acid (1.68 g, 8.2 mmol) in anhydrous tetrahydrofuran (24 mL) was added EDC (1.53 g, 9.9 mmol) followed by HOBt (1.22 g, 9.1 mmol) and the reaction mixture was allowed to stir for 1 h at room temperature. A solution of pyrrolidine (1.03 ml, 12.4 mmol) in tetrahydrofuran (8 mL) was added and the reaction mixture was allowed to stir overnight at room temperature. The solvent was removed under reduced pressure and residue partitioned between ethyl acetate and 1 M aqueous potassium carbonate. The organic layer was dried (Na2SO4) and solvent evaporated under reduced pressure. Purification by flash column chromatography (silica, EtOAc/MeOH 9:1) afforded the title compound (95%). 1H NMR (300 MHz, CDCl3): 7.79 (s, 1H), 3.92 (s, 3H), δ 3.35 (bs, 4H), δ 1.97 (bs, 4H). LCMS (ESI+) 257.0 (MH+).

후처리

  1. stirringto stir overnight at room temperature
  2. customThe solvent was removed under reduced pressure and residue
  3. custompartitioned between ethyl acetate and 1 M aqueous potassium carbonate
  4. dry with materialThe organic layer was dried (Na2SO4) and solvent
  5. customevaporated under reduced pressure
  6. customPurification by flash column chromatography (silica, EtOAc/MeOH 9:1)

출처 및 근거

ORD 기록
ord-eee055c2a97d44ef96e38b2f22e0b907
출처 데이터셋
uspto-grants-2010_09
특허 번호
US07803825B2

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