Diethyl Ether → 2-methyl-1-(1H-pyrrolo[2,3-c]pyridin-2-yl)-1-propanol

HRID 1821875노트

반응식

HRID 1821875 반응식
[NH:1]1[C:5]2=[CH:6][N:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[C:2]1[CH:10]=[O:11].[CH:12]([Mg]Br)([CH3:14])[CH3:13].C(OCC)C.[Cl-].[NH4+]>O1CCCC1.O>[CH3:13][CH:12]([CH3:14])[CH:10]([C:2]1[NH:1][C:5]2=[CH:6][N:7]=[CH:8][CH:9]=[C:4]2[CH:3]=1)[OH:11]

참가 물질

7

반응물 4

HCID 3283Diethyl Ether2회HCID 25517Ammonium ChlorideHCID 468564601H-pyrrolo[2,3-c]pyridine-2-carbaldehydeHCID 178418365HCID 178418365, 화합물2회

생성물 1

HCID 578934892-methyl-1-(1H-pyrrolo[2,3-c]pyridin-2-yl)-1-propanol수율 53%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

1H-Pyrrolo[2,3-c]pyridine-2-carboxaldehyde (125 mg, 0.86 mmol) was suspended in tetrahydrofuran (5 mL) at −30° C. under a nitrogen atmosphere. Isopropylmagnesium bromide in diethyl ether (0.87 mL, 1.74 mmol) was added dropwise. The reaction mixture was slowly warmed to room temperature. After stirring for ca. 3 h, the reaction mixture was cooled to −30° C. and additional 2.0 M isopropylmagnesium bromide in diethyl ether (0.22 mL, 0.44 mmol) was added. The reaction mixture was stirred for another 1 h, while warming to room temperature. The reaction mixture was poured into a 2:1 solution of saturated ammonium chloride and water, and extracted with ethyl acetate (3×). The combined organic extracts were washed with water and brine, dried over sodium sulfate, and concentrated. The crude product was purified by Biotage chromatography (2 to 10% methanol in methylene chloride) to provide 2-methyl-1-(1H-pyrrolo[2,3-c]pyridin-2-yl)-1-propanol (86 mg, 53%) as a white solid: mp 140-144° C.; 1H NMR (500 MHz, CD3OD) δ0.99 (6H, m), 2.01-2.25 (1H, m), 4.57-4.65 (1H, m), 6.38 (1H, s), 7.51 (1H, s), 8.00 (1H, s), 8.63 (1H, s); ESI MS m/z 191 [C11H14N2O+H]+; HPLC (Method A) >99% (AUC), tR=13.1 min.

후처리

  1. temperaturethe reaction mixture was cooled to −30° C.
  2. stirringThe reaction mixture was stirred for another 1 h
  3. temperaturewhile warming to room temperature
  4. extractionextracted with ethyl acetate (3×)
  5. washThe combined organic extracts were washed with water and brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customThe crude product was purified by Biotage chromatography (2 to 10% methanol in methylene chloride)

출처 및 근거

ORD 기록
ord-272eba314c934fa1b648e49d838a38ab
출처 데이터셋
uspto-grants-2009_10
특허 번호
US07608627B2

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