4-Toluenesulfonyl chloride → Methyl 6-(chloromethyl)nicotinate

HRID 1838796Notes

Reaction equation

HRID 1838796 reaction equation
C1(C)C=CC(S([Cl:10])(=O)=O)=CC=1.[CH3:12][C:13]1[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][N+:14]=1[O-]>O1CCOCC1>[Cl:10][CH2:12][C:13]1[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][N:14]=1

Participants

4

Reactant 2

HCID 73974-Toluenesulfonyl chlorideHCID 15883477Methyl 6-methylnicotinate 1-oxide

Product 1

HCID 15331516Methyl 6-(chloromethyl)nicotinateYield 60.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

p-Toluenesulfonyl chloride (10.7 g, 56.1 mmol) was combined with 13 (7.8 g, 51.0 mmol) in dioxane (100 ml) under an Argon atmosphere. The reaction mixture was heated under reflux for 1 night. After cooling to room temperature the solvent was evaporated and the residue dissolved in dichloromethane (200 ml). The solution was washed with saturated Na2CO3 (aq) (2×100 ml), brine (50 ml) and dried (Na2SO4). After evaporation of the solvent the product was purified by column chromatography (SiO2, hexane/ethyl acetate 10:2.5) to give 14 (5.71 g, 30.8 mmol, 60%) as a slightly yellow solid. An analytically pure sample could be obtained by recrystallization from n-hexane, mp 63.5-63.8° C.; 1H-NMR (CDCl3) δ3.94 (s, 3H), 4.70 (s, 2H), 7.58 (d, 1H, J=8.4 Hz), 8.30 (dd, 1H, J 8.1 Hz, J=2.2 Hz), 9.08 (d, 1H, J=1.5 Hz); Anal. Calcd. for C8H8ClNO2: C 51.77, H 4.34, N 7.55; found: C 51.50, H 4.23, N 7.46.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureunder reflux for 1 night
  3. customwas evaporated
  4. dissolutionthe residue dissolved in dichloromethane (200 ml)
  5. washThe solution was washed with saturated Na2CO3 (aq) (2×100 ml), brine (50 ml)
  6. dry with materialdried (Na2SO4)
  7. customAfter evaporation of the solvent the product
  8. customwas purified by column chromatography (SiO2, hexane/ethyl acetate 10:2.5)

Sources & evidence

ORD record
ord-23faad318dd34332ae04398d7088a058
Source dataset
uspto-grants-2004_01
Patent number
US06677288B2

Reaction notes

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