Thionyl Chloride → Methyl 6-(chloromethyl)nicotinate

HRID 1176200Notes

Reaction equation

HRID 1176200 reaction equation
S(Cl)([Cl:3])=O.[CH3:5][O:6][C:7](=[O:16])[C:8]1[CH:13]=[CH:12][C:11]([CH2:14]O)=[N:10][CH:9]=1>C(Cl)(Cl)Cl>[CH3:5][O:6][C:7](=[O:16])[C:8]1[CH:13]=[CH:12][C:11]([CH2:14][Cl:3])=[N:10][CH:9]=1

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 7894146-Hydroxymethyl-nicotinic acid methyl ester

Product 1

HCID 15331516Methyl 6-(chloromethyl)nicotinateYield 90%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

Thionyl chloride (5.0 ml, 2.0 eq) was added dropwise to a solution of alcohol (III, 5.7 g) in anhydrous chloroform (50 mL) cooling with a water bath. The resulting solution was stirred at room temperature for 2 hours. The reaction was quenched with saturated aqueous sodium bicarbonate solution followed by CH2Cl2 extractions. The combined organic layers were dried over MgSO4 and filtered. The filtrate was concentrated in vacuo and then passed through a silica gel pad (eluent 5% MeOH in CH2Cl2) to afford the desired product (7.0 g, 90%) as a off-white solid. MS-ESI m/z 186.09 (M+H)+; 1H NMR (CDCl3) δ 9.18 (d, J=2 Hz, 1H), 8.35 (dd, J=2 and 8.5 Hz, 1H), 7.61 (d, J=8.5 Hz, 1H), 4.74 (s, 2H), 3.98 (s, 3H) ppm.

Workup

  1. temperaturecooling with a water bath
  2. customThe reaction was quenched with saturated aqueous sodium bicarbonate solution
  3. extractionfollowed by CH2Cl2 extractions
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-efef5eb73f2841b6af9ff7a8444a9dda
Source dataset
uspto-grants-2010_11
Patent number
US07842813B2

Reaction notes

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