Water → 5-Chloro-α-cyclohexyl-1H-pyrrolo[2,3-b]pyridine-4-methanol

HRID 1854481Notes

Reaction equation

HRID 1854481 reaction equation
[Cl:1][C:2]1[CH:7]=[N:6][C:5]2[NH:8][CH:9]=[CH:10][C:4]=2[C:3]=1[CH:11]=[O:12].[CH:13]1([Mg]Cl)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1.O>C1COCC1>[Cl:1][C:2]1[C:3]([CH:11]([CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)[OH:12])=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 962WaterHCID 242292805-Chloro-1H-pyrrolo[2,3-b]pyridine-4-carbaldehydeHCID 178478990HCID 178478990, compound2×

Product 1

HCID 580100785-Chloro-α-cyclohexyl-1H-pyrrolo[2,3-b]pyridine-4-methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-chloro-1H-pyrrolo[2,3-b]pyridine-4-carbaldehyde (3.0 g, 16 mmol, Adesis) in THF (100 mL) at about 0° C. was added cyclohexylmagnesium chloride (2 M in Et2O, 22.8 mL, 45.7 mmol). The reaction mixture was stirred at ambient temperature for about 2 h, then additional cyclohexylmagnesium chloride (2 M in Et2O, 8.3 mL, 16.6 mmol) was added. The reaction mixture was stirred at ambient temperature for about 16 h. Water (10 mL) was added to quench the reaction and the volatiles were removed under reduced pressure. The product was extracted into DCM (3×20 mL) and the combined organic phases were dried over anhydrous MgSO4 and filtered. The solvent was removed under reduced pressure and the crude material was purified by chromatography over silica gel using a gradient of 10 to 45% EtOAc in heptane as the eluent to provide (5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)(cyclohexyl)methanol as an off white solid (1.97 g, 45%): LC/MS (Table 2, Method a) Rt=2.32 min; MS m/z: 265 and 267 (M+H)+.

Workup

  1. stirringThe reaction mixture was stirred at ambient temperature for about 16 h
  2. customto quench
  3. customthe reaction
  4. customthe volatiles were removed under reduced pressure
  5. extractionThe product was extracted into DCM (3×20 mL)
  6. dry with materialthe combined organic phases were dried over anhydrous MgSO4
  7. filtrationfiltered
  8. customThe solvent was removed under reduced pressure
  9. customthe crude material was purified by chromatography over silica gel using a gradient of 10 to 45% EtOAc in heptane as the eluent

Sources & evidence

ORD record
ord-d9e018d360f34121bf5b54f9d1eebb68
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

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