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

HRID 1867100Notes

Reaction equation

HRID 1867100 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N+:3]=1[O-].C1(C)C=CC(S([Cl:22])(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>O1CCOCC1>[Cl:22][CH2:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 15883477Methyl 6-methylnicotinate 1-oxide

Product 1

HCID 15331516Methyl 6-(chloromethyl)nicotinate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Methyl 6-methylnicotinate 1-oxide (from Step 1) (6.0 g, 35.9 mmol) was added into the p-toluenesulfonyl chloride (10 g, 52.4 mmol) in 100 mL of 1,4-dioxane. The mixture was heated to reflux for 20 hours. Saturated sodium bicarbonate solution (200 ml) was added into the reaction and the mixture was transferred to separatory funnel. The compound was extracted using ethyl acetate (300 ml×2) and the combined ethyl acetate solution was dried over magnesium sulfate and evaporated to black solid (5.2 g, 78%). LC/MS, tr=1.52 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.). ES-MS m/z 186 (M+H). ES-HRMS m/z 186.0314 (M+H calcd for C8H9ClNO2 requires 186.0316).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 20 hours
  3. customthe mixture was transferred to separatory funnel
  4. extractionThe compound was extracted
  5. dry with materialthe combined ethyl acetate solution was dried over magnesium sulfate
  6. customevaporated to black solid (5.2 g, 78%)
  7. customLC/MS, tr=1.52 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.)

Sources & evidence

ORD record
ord-764cc177f6794970a96927a629ba2407
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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