Acetic Acid → (7-Chloro-2-dimethylaminomethyl-quinolin-8-yl)-acetic acid ethyl ester

HRID 505222Notes

Reaction equation

HRID 505222 reaction equation
[CH3:1][NH:2][CH3:3].[CH2:4]([O:6][C:7](=[O:22])[CH2:8][C:9]1[C:10]([Cl:21])=[CH:11][CH:12]=[C:13]2[C:18]=1[N:17]=[C:16]([CH:19]=O)[CH:15]=[CH:14]2)[CH3:5].[BH3-]C#N.[Na+].C(O)(=O)C.C([O-])(O)=O.[Na+]>C1COCC1.CO.O>[CH2:4]([O:6][C:7](=[O:22])[CH2:8][C:9]1[C:10]([Cl:21])=[CH:11][CH:12]=[C:13]2[C:18]=1[N:17]=[C:16]([CH2:19][N:2]([CH3:3])[CH3:1])[CH:15]=[CH:14]2)[CH3:5]

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 674DimethylamineHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 86253926(7-Chloro-2-formyl-quinolin-8-yl)-acetic acid ethyl ester

Product 1

HCID 66882457(7-Chloro-2-dimethylaminomethyl-quinolin-8-yl)-acetic acid ethyl esterYield 78%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Dimethylamine (5.6 M solution in EtOH, 0.27 ml, 1.54 mmol, 1.5 equiv) was added to a solution of (7-chloro-2-formyl-quinolin-8-yl)-acetic acid ethyl ester (285 mg, 1.03 mmol) in anhydrous THF (5 ml). The reaction mixture was stirred at room temperature for 18 hours. A solution of NaCNBH3 (77 mg, 1.23 mmol, 1.2 equiv) in methanol (2 ml) was added, immediately followed by the addition of acetic acid (308 mg, 5.13 mmol, 5.0 equiv). After 5 minutes at room temperature, TLC analysis indicated complete conversion. The reaction mixture was diluted with water, adjusted to pH=8 with concentrated aqueous NaHCO3 solution, and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified via flash chromatography (gradient of CH2Cl2/MeOH 99:1 to 90:10) to afford the title compound (245 mg, 78%) as a colorless solid. 1H NMR (400 MHz, d6-DMSO): δ=8.45 (d, J=8.1 Hz, 1H), 7.98 (d, J=8.4 Hz, 1H), 7.69 (d, J=8.4 Hz, 1H), 7.63 (d, J=8.1 Hz, 1H), 4.47 (s, 2H), 4.08 (q, J=7.3 Hz, 2H), 2.50 (s, 6H), 1.16 (t, J=7.3 Hz, 3H). MS (ES+): 307.3 (M+H)+.

Workup

  1. waitAfter 5 minutes at room temperature
  2. extractionextracted with EtOAc
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified via flash chromatography (gradient of CH2Cl2/MeOH 99:1 to 90:10)

Sources & evidence

ORD record
ord-dd2ec6f307bc466a83e1f698f896ed63
Source dataset
uspto-grants-2010_08
Patent number
US07781438B2

Reaction notes

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