Sulfuric Acid → 6-[3-(1-Methyl-piperidin-4-yl)-propoxy]-pyridine-3-carbaldehyde

HRID 2420976Notes

Reaction equation

HRID 2420976 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([CH2:8][CH2:9][CH2:10][O:11][C:12]2[CH:19]=[CH:18][C:15]([C:16]#N)=[CH:14][N:13]=2)[CH2:4][CH2:3]1.CC(C[AlH]CC(C)C)C.[OH:29]S(O)(=O)=O.C([O-])(O)=O.[Na+].C(C(C(C([O-])=O)O)O)([O-])=O.[K+].[Na+]>C1(C)C=CC=CC=1.CO>[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([CH2:8][CH2:9][CH2:10][O:11][C:12]2[N:13]=[CH:14][C:15]([CH:16]=[O:29])=[CH:18][CH:19]=2)[CH2:4][CH2:3]1

Participants

8

Reactant 5

HCID 1118Sulfuric AcidHCID 14487Diisobutylaluminum hydrideHCID 516892Sodium BicarbonateHCID 9855836Potassium sodium tartarateHCID 574347676-[3-(1-Methyl-piperidin-4-yl)-propoxy]-nicotinonitrile

Product 1

HCID 575254546-[3-(1-Methyl-piperidin-4-yl)-propoxy]-pyridine-3-carbaldehydeYield 92%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent

Procedure

To a 0° C. solution of 6-[3-(1-methyl-piperidin-4-yl)-propoxy]-nicotinonitrile (640 mg, 2.47 mmol) in toluene (20 mL) was added 1.0 M DIBAL-H in hexanes (3.70 mL, 3.70 mmol) dropwise. The mixture was warmed to rt and stirred for 2 h (complete by TLC). Methanol was added (5 mL) followed by 1.0 M H2SO4 (±0 mL). After stirring for 30 min the solution was neutralized with satd. aq. NaHCO3, diluted with satd. aq. sodium potassium tartrate (10 mL), and stirred an additional 30 min. The reaction was extracted with CHCl3 (3×50 mL) and the combined extracts were dried (Na2SO4), filtered, and concentrated, yielding the crude product, which was purified by Method 1 to afford 598 mg (92%) of a colorless oil. MS (ESI): mass calcd for C15H22N2O2, 262.17; m/z found, 263.1 [M+H]+. 1H NMR (400 MHz, CDCl3): 9.87 (br s, 1H), 8.53 (d, J=2.3, 1H), 7.98 (dd, J=8.6, 2.3, 1H), 6.74 (d, J=8.6, 1H), 4.34 (t, J=6.6, 2H), 2.78-2.26 (m, 2H), 2.19 (s, 3H), 1.85-1.62 (m, 7H), 1.35-1.16 (m, 4H).

Workup

  1. stirringAfter stirring for 30 min the solution
  2. extractionThe reaction was extracted with CHCl3 (3×50 mL)
  3. dry with materialthe combined extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customyielding the crude product, which
  7. customwas purified by Method 1

Sources & evidence

ORD record
ord-f77f88e1cc6245e0bb81c4edd742b7bf
Source dataset
uspto-grants-2011_06
Patent number
US07956066B2

Reaction notes

Loading…