Sodium Hydroxide → 2-bromo-4-[[[(1H-indol-4-yl)methyl]amino]carbonyl]benzoic acid

HRID 1058407

반응식

HRID 1058407 반응식
[OH-].[Na+].C[O:4][C:5](=[O:26])[C:6]1[CH:11]=[CH:10][C:9]([C:12]([NH:14][CH2:15][C:16]2[CH:24]=[CH:23][CH:22]=[C:21]3[C:17]=2[CH:18]=[CH:19][NH:20]3)=[O:13])=[CH:8][C:7]=1[Br:25]>O1CCCC1.CO.C(OCC)(=O)C>[Br:25][C:7]1[CH:8]=[C:9]([C:12]([NH:14][CH2:15][C:16]2[CH:24]=[CH:23][CH:22]=[C:21]3[C:17]=2[CH:18]=[CH:19][NH:20]3)=[O:13])[CH:10]=[CH:11][C:6]=1[C:5]([OH:26])=[O:4]

참가 물질

5

반응물 2

HCID 14798Sodium Hydroxide2회HCID 235607692-bromo-4-[[[(1H-indol-4-yl)methyl]amino]carbonyl]benzoic acid methyl ester

생성물 1

HCID 226613302-bromo-4-[[[(1H-indol-4-yl)methyl]amino]carbonyl]benzoic acid

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 21899815MeOH tetrahydrofuran용매

실험 절차

Sodium hydroxide (21.5 mg, 0.54 mmol) was added to a solution of 2-bromo-4-[[[(1H-indol-4-yl)methyl]amino]carbonyl]benzoic acid methyl ester (Example 83; 208 mg, 0.54 mmol) in tetrahydrofuran/methanol (2:1; 1.8 mL). The solution was allowed to stir at room temperature for 4 h and then more sodium hydroxide (21.5 mg, 0.54 mmol) was added. The solution was allowed to stir at room temperature overnight, then it was diluted with ethyl acetate and the solution was washed with 1N hydrochloric acid solution (10 mL), washed with brine, dried (MgSO4), filtered and concentrated to give crude 2-bromo-4-[[[(1H-indol-4-yl)methyl]amino]carbonyl]benzoic acid. This was mixed with a solution of rac.-2-(dimethoxyphosphinyl)glycine methyl ester (Example 125) freshly prepared from rac.-N-(benzyloxycarbonyl)-2-(dimethoxyphosphinyl)glycine methyl ester (213.5 mg, 0.64 mmol), O-(benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (203.5 mg, 0.54 mmol), 1-hydroxybenzotriazole (72.6 mg, 0.54 mmol) and diisopropylethylamine (281 μL, 1.61 mmol) in N,N-dimethylformamide (1.5 mL). The solution was allowed to stir for 3 h, then ethyl acetate (20 mL) was added. The solution was washed with 1N hydrochloric acid solution (10 mL), saturated sodium bicarbonate solution (15 mL) and each aqueous layer was back-extracted with ethyl acetate. The combined organic layers were washed with brine (10 mL), dried (MgSO4), filtered, evaporated and chromatographed over silica gel (3-5% methanol/dichloromethane) to give rac.-N-[2-bromo-4-[[[(1H-indol-4-yl)methyl]amino]carbonyl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (206.8 mg, 69% yield) as a pale yellow solid.

후처리

  1. stirringto stir at room temperature overnight
  2. washthe solution was washed with 1N hydrochloric acid solution (10 mL)
  3. washwashed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated

출처 및 근거

ORD 기록
ord-18eccf059802409ca50b5d2c3b2156c2
출처 데이터셋
uspto-grants-2003_02
특허 번호
US06515124B2

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