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

HRID 1821875Notes

Reaction equation

HRID 1821875 reaction equation
[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]

Participants

7

Reactant 4

HCID 3283Diethyl Ether2×HCID 25517Ammonium ChlorideHCID 468564601H-pyrrolo[2,3-c]pyridine-2-carbaldehydeHCID 178418365HCID 178418365, compound2×

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-272eba314c934fa1b648e49d838a38ab
Source dataset
uspto-grants-2009_10
Patent number
US07608627B2

Reaction notes

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