Dimethyl Sulfate → Ethyl 6-chloro-1,2-dihydro-1-methyl-2-(trifluoro-methyl)-3-quinolinecarboxylate

HRID 2297894Notes

Reaction equation

HRID 2297894 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]([C:12]([F:15])([F:14])[F:13])[C:6]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:5]2.[OH-].[Na+].S(OC)(O[CH3:27])(=O)=O.CCCCCC>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:27])[CH:7]([C:12]([F:15])([F:14])[F:13])[C:6]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:5]2

Participants

7

Reactant 4

HCID 6497Dimethyl SulfateHCID 8058HexaneHCID 14798Sodium HydroxideHCID 21883646Ethyl 6-chloro-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylate

Product 1

HCID 21883533Ethyl 6-chloro-1,2-dihydro-1-methyl-2-(trifluoro-methyl)-3-quinolinecarboxylateYield 90%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6344DichloromethaneSolvent

Procedure

Ethyl 6-chloro-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylate (Example 157, Step 2) (1.28 g, 4.21 mmol), tetrabutylammonium iodide (0.36 g, 0.92 mmol) and aqueous NaOH (50%, 2 mL) were stirred vigorously in methylene chloride (40 mL). Dimethyl sulfate (2.12 g, 16.84 mmol) was added to the dark orange mixture via syringe over 2 hours. Hexane (5 mL) was added, and the solution was washed with water (2×20 mL), saturated ammonium chloride solution (2×20 mL), dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo to afford the crude ester as a yellow solid. The solid was purified by flash chromatography (silica gel,50 g; ethyl acetate-hexanes, 1:19) to yield, upon concentration of the appropriate fractions, ethyl 6-chloro-1,2-dihydro-1-methyl-2-(trifluoromethyl)-3-quinoline-carboxylate (1.2 g, 90% yield): mp 118-120° C. 1H NMR (CD3OD/300 MHz) 7.71 (s, 1H), 7.30-7.26 (m, 2H), 6.77-6.74 (m, 1H), 5.12 (q, 1H, J=6.8 Hz), 4.44-4.22 (m, 2H), 3.18 (s, 3H), 1.35 (t, 3H, J=7.0 Hz). EIHRMS m/z 320.0701 (M−H, Calc'd 320.0665) Anal. Calc'd for C14H13F3NO2Cl: C, 52.60; H, 4.10; N, 4.38. Found: C, 52.57; H, 4.14; N, 4.32.

Workup

  1. washthe solution was washed with water (2×20 mL), saturated ammonium chloride solution (2×20 mL)
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated in vacuo
  5. customto afford the crude ester as a yellow solid
  6. customThe solid was purified by flash chromatography (silica gel,50 g; ethyl acetate-hexanes, 1:19)

Sources & evidence

ORD record
ord-b0e26e94e5134246851605eb2a53816a
Source dataset
uspto-grants-2002_12
Patent number
US06492390B2

Reaction notes

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