Isopropanol → 6-Chloro-5-methylnicotinic acid isopropyl ester

HRID 1908785Notes

Reaction equation

HRID 1908785 reaction equation
[Cl:1][C:2]1[C:10]([CH3:11])=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][N:3]=1.[CH:12](O)([CH3:14])[CH3:13]>C[Si](Cl)(C)C.C(OCC)C>[CH:12]([O:7][C:6](=[O:8])[C:5]1[CH:9]=[C:10]([CH3:11])[C:2]([Cl:1])=[N:3][CH:4]=1)([CH3:14])[CH3:13]

Participants

5

Reactant 2

HCID 3776IsopropanolHCID 123877296-Chloro-5-methylnicotinic acid

Product 1

HCID 866505246-Chloro-5-methylnicotinic acid isopropyl ester

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6397ChlorotrimethylsilaneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 6-chloro-5-methyl-nicotinic acid (21.64 g, 126 mmol) in isopropanol (450 mL), trimethylsilyl chloride (160 mL) is added dropwise. Upon completion of the addition, the mixture is heated to 70° C. and stirring is continued for 18 h. The mixture is diluted with diethyl ether (500 mL) and washed with sat. aq. NaHCO3 solution (5×50 mL). The washings are extracted back with diethyl ether (100 mL). The combined org. extracts are dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 6:1 to give 6-chloro-5-methyl-nicotinic acid isopropyl ester (6.09 g) as a colourless oil; LC-MS: tR=0.97 min, [M+1]+=214.03. 1H NMR (D6-DMSO): δ 1.34 (d, J=6.3 Hz, 6H), 2.41 (s, 3H), 5.11-5.22 (m, 1H), 8.27 (s, 1H), 8.73 (s, 1H).

Workup

  1. additionUpon completion of the addition
  2. washwashed with sat. aq. NaHCO3 solution (5×50 mL)
  3. extractionThe washings are extracted back with diethyl ether (100 mL)
  4. dry with materialextracts are dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product is purified by CC on silica gel eluting with heptane:EA 6:1

Sources & evidence

ORD record
ord-b02d00f0cf714579a65f5fb8f2573ecf
Source dataset
uspto-grants-2013_12
Patent number
US08598208B2

Reaction notes

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