Pyridine → HCID 57525450, compound

HRID 1445158Notes

Reaction equation

HRID 1445158 reaction equation
[CH3:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][CH2:13][C:14]2[CH2:15][CH2:16][N:17]([CH3:20])[CH2:18][CH:19]=2)[CH:7]=[CH:6][C:3]=1[CH:4]=O.C[N:22]1CC=[C:25]([CH2:28][CH2:29][CH2:30]O)[CH2:24][CH2:23]1.N1C=CC=CC=1.C1(C)C=CC(S([Cl:47])(=O)=O)=CC=1.OC1C=CC(C=O)=C(C)C=1.C([O-])([O-])=O.[K+].[K+].C[N:66]([CH:68]=O)C>ClCCl.O>[Cl:47][C:25]1[CH:28]=[C:29]([CH3:30])[C:68]2[N:66]=[C:4]([C:3]3[CH:6]=[CH:7][C:8]([O:10][CH2:11][CH2:12][CH2:13][C:14]4[CH2:15][CH2:16][N:17]([CH3:20])[CH2:18][CH:19]=4)=[CH:9][C:2]=3[CH3:1])[NH:22][C:23]=2[CH:24]=1

Participants

10

Reactant 7

HCID 1049PyridineHCID 6228DimethylformamideHCID 73974-Toluenesulfonyl chlorideHCID 11430Potassium CarbonateHCID 4581854-Hydroxy-2-methylbenzaldehydeHCID 57434761HCID 57434761, compoundHCID 57525451HCID 57525451, compound

Product 1

HCID 57525450HCID 57525450, compoundYield 9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

2-Methyl-4-[3-(1-methyl-1,2,3,6-tetrahydro-pyridin-4-yl)-propoxy]-benzaldehyde. To a solution of 3-(1-methyl-1,2,3,6-tetrahydro-pyridin-4-yl)-propan-1-ol (2.24 g, 14.5 mmol, 1.0 equiv) and pyridine (1.64 mL, 20.2 mmol, 1.4 equiv) in dichloromethane (50 mL) at 0° C. was added p-toluenesulfonyl chloride (3.85 g, 20.2 mmol, 1.4 equiv). The reaction mixture, which was allowed to warm to rt, was stirred for 12 h and then poured into water. The aqueous mixture was extracted with dichloromethane and the extract was dried (Na2SO4), filtered, and concentrated. The residue was subjected to column chromatography on silica gel (10% methanol in dichloromethane) and the resulting oil was added to a mixture of 4-hydroxy-2-methyl-benzaldehyde (639 mg, 4.69 mmol) and K2CO3 (1.62 g, 11.7 mmol) in DMF and warmed to 100° C. After stirring for 16 h, the mixture was allowed to cool to rt and filtered through a pad of diatomaceous earth. The diatomaceous earth was rinsed with ethyl acetate, and the filtrate was concentrated. The residue was purified by Method 2 to afford 356 mg (9%) of the title compound. 1H NMR (400 MHz, CD3OD): 10.1 (s, 1H), 7.78 (d, J=8.6 Hz, 1H), 6.92 (dd, J=8.6, 2.4 Hz, 1H), 6.84 (d, J=2.1 Hz, 1H), 5.49-5.43 (m, 1H), 4.09 (t, J=6.3 Hz, 2H), 2.97-2.91 (m, 2H), 2.65-2.57 (m, 5H), 2.35 (s, 3H), 2.25-2.16 (m, 4H), 1.99-1.88 (m, 2H).

Workup

  1. extractionThe aqueous mixture was extracted with dichloromethane
  2. dry with materialthe extract was dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. temperaturewarmed to 100° C
  6. stirringAfter stirring for 16 h
  7. temperatureto cool to rt
  8. filtrationfiltered through a pad of diatomaceous earth
  9. washThe diatomaceous earth was rinsed with ethyl acetate
  10. concentrationthe filtrate was concentrated
  11. customThe residue was purified by Method 2

Sources & evidence

ORD record
ord-e8e11f54e3d34f3b80e090ef29501410
Source dataset
uspto-grants-2010_02
Patent number
US07662966B2

Reaction notes

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