Sulfuric Acid → 2-[4-(1-Methyl-piperidin-4-yl)-butoxy]-pyridine-4-carbaldehyde

HRID 2420981Notes

Reaction equation

HRID 2420981 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:14]=[C:15]([CH:18]=[CH:19][N:20]=2)[C:16]#N)[CH2:4][CH2:3]1.CC(C[AlH]CC(C)C)C.[OH:30]S(O)(=O)=O.[OH-].[Na+].C(C(C(C([O-])=O)O)O)([O-])=O.[K+].[Na+]>C1(C)C=CC=CC=1.C(Cl)Cl.CO>[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:14]=[C:15]([CH:16]=[O:30])[CH:18]=[CH:19][N:20]=2)[CH2:4][CH2:3]1

Participants

9

Reactant 5

HCID 1118Sulfuric AcidHCID 14487Diisobutylaluminum hydrideHCID 14798Sodium HydroxideHCID 9855836Potassium sodium tartarateHCID 574528642-[4-(1-Methyl-piperidin-4-yl)-butoxy]-isonicotinonitrile

Product 1

HCID 860738872-[4-(1-Methyl-piperidin-4-yl)-butoxy]-pyridine-4-carbaldehydeYield 64%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1140TolueneSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2-[4-(1-methyl-piperidin-4-yl)-butoxy]-isonicotinonitrile (0.44 g, 1.61 mmol) in toluene (5 mL) at 0° C. was added a 1.5 M DIBAL-H in toluene (2.41 mL, 2.41 mmol). The reaction mixture was allowed to warm to rt. After 3 h, methanol (8 mL) and 1.0 M H2SO4 (5 mL) were added dropwise. After 30 min, the mixture was neutralized with 1.0 M NaOH (10 mL) followed by addition of satd. aq. sodium potassium tartrate (40 mL) and CH2Cl2 (100 mL). After 30 min the mixture was extracted with CHCl3 (3×50 mL) and washed with brine. The organic layer was dried (Na2SO4), filtered, and concentrated. Purification of the mixture by Method 1 afforded 318 mg (64%) of the title compound. 1H NMR (400 MHz, CDCl3): 10.0 (s, 1H), 8.34 (d, J=5.3, 1H), 7.28 (d, J=1.3, 1H), 7.14-7.12 (m, 1H), 4.33 (t, J=6.6, 2H), 2.87-2.80 (m, 2H), 2.25 (s, 3H), 1.93-1.65 (m, 6H), 1.52-1.42 (m, 2H), 1.35-1.07 (m, 5H).

Workup

  1. waitAfter 30 min
  2. additionfollowed by addition of satd
  3. extractionAfter 30 min the mixture was extracted with CHCl3 (3×50 mL)
  4. washwashed with brine
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the mixture by Method 1

Sources & evidence

ORD record
ord-2685c45aa0f4431aa8b2330431482b1b
Source dataset
uspto-grants-2011_06
Patent number
US07956066B2

Reaction notes

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