Sodium Chloride → Tert-butyl 5-pyridin-4-yl-indole-1-carboxylate

HRID 1983994

반응식

HRID 1983994 반응식
[N:1]1[CH:6]=[CH:5][C:4](B(O)O)=[CH:3][CH:2]=1.Br[C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[N:16]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH:15]=[CH:14]2.C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1.C(O)C>[N:1]1[CH:6]=[CH:5][C:4]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH:15]=[CH:14]3)=[CH:3][CH:2]=1

참가 물질

8

반응물 4

HCID 5234Sodium ChlorideHCID 10340Sodium CarbonateHCID 2728482N-Boc-5-bromoindoleHCID 2734379(Pyridin-4-yl)boronic acid2회

생성물 1

HCID 68857022Tert-butyl 5-pyridin-4-yl-indole-1-carboxylate수율 216.6%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 702Ethanol용매HCID 1140Toluene용매

실험 절차

A mixture of pyridine-4-boronic acid (5.0 g, 0.041 mol), tert-butyl 5-bromo-indole-1-carboxylate (11.8 g, 0.04 mol), 2 M aqueous sodium carbonate (80 mL, 0.16 mol), tetrakis(triphenylphosphine)palladium(0) (0.92 g, 0.0008 mol), ethanol (19 mL) and toluene (175 mL) was boiled under reflux for 12 h. The experiment was repeated with the double amount of starting materials, e.g. 10 g of pyridine-4-boronic acid. The combined reaction mixture from the two experiments was poured onto a saturated sodium chloride solution (brine), and the aqueous phase was extracted with ethyl acetate. The combined organic phase was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography (ethyl acetate followed by ethyl acetate/triethylamine 95:5) to give tert-butyl 5-pyridin-4-yl-indole-1-carboxylate (25.5 g, 61%), which was dissolved in a mixture of methanol (500 mL), tetrahydrofuran (200 mL) and 15% aqueous sodium hydroxide (25 mL). The mixture was boiled under reflux for 1 h, concentrate in vacuo to 200 mL and poured onto brine. The aqueous phase was extracted with a mixture of ethyl acetate and tetrahydrofuran, and the combined organic phase was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was precipitated from a cold mixture of methanol and tetrahydrofuran to give the title compound as a creamy solid (9.5 g, 54%). A second crop of the title compound was obtained from the mother liquor (1.7 g, 9%).

후처리

  1. temperatureunder reflux for 12 h
  2. customThe combined reaction mixture from the two experiments
  3. extractionthe aqueous phase was extracted with ethyl acetate
  4. washThe combined organic phase was washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography (ethyl acetate followed by ethyl acetate/triethylamine 95:5)

출처 및 근거

ORD 기록
ord-90834d7dda1747bf9e19c37233851c95
출처 데이터셋
uspto-grants-2009_06
특허 번호
US07544685B2

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