Dimethylformamide → (S)-2-[2-cyclopropyl-8-fluoro-4-methyl-3-(4-pyrazol-1-ylbenzyl)quinolin-5-yloxy]propionic acid methyl ester

HRID 1922161

Reaction equation

HRID 1922161 reaction equation
[CH:1]1([C:4]2[C:13]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([N:21]4[CH:25]=[CH:24][CH:23]=[N:22]4)=[CH:17][CH:16]=3)=[C:12]([CH3:26])[C:11]3[C:10]([OH:27])=[CH:9][CH:8]=[C:7]([F:28])[C:6]=3[N:5]=2)[CH2:3][CH2:2]1.CN(C)C=O.C(=O)([O-])[O-].[K+].[K+].[CH3:40][O:41][C:42](=[O:46])[C@H:43](Cl)[CH3:44]>O>[CH3:40][O:41][C:42](=[O:46])[C@@H:43]([O:27][C:10]1[CH:9]=[CH:8][C:7]([F:28])=[C:6]2[C:11]=1[C:12]([CH3:26])=[C:13]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]3[CH:25]=[CH:24][CH:23]=[N:22]3)=[CH:17][CH:16]=1)[C:4]([CH:1]1[CH2:2][CH2:3]1)=[N:5]2)[CH3:44]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 149593Methyl 2-chloropropanoate, (R)-HCID 1363483632-Cyclopropyl-8-fluoro-4-methyl-3-(4-pyrazol-1-ylbenzyl)quinolin-5-ol

Product 1

HCID 67457321(S)-2-[2-cyclopropyl-8-fluoro-4-methyl-3-(4-pyrazol-1-ylbenzyl)quinolin-5-yloxy]propionic acid methyl esterYield 41.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of 2-cyclopropyl-8-fluoro-4-methyl-3-(4-pyrazol-1-ylbenzyl)quinolin-5-ol (0.064 g), N,N-dimethylformamide (0.86 mL), potassium carbonate (0.071 g) and (R)-2-chloropropionic acid methyl ester (0.032 g) was stirred at 40° C. for 3 days. The mixture was cooled to 0° C., diluted with water (40 mL) and extracted with ethyl acetate (3×10 mL). The combined extracts were washed saturated aqueous sodium chloride solution, dried over magnesium sulfate and concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel, eluting with a mixture of ethyl acetate and cyclohexane (0:1 to 4:6 by volume) gave title compound as a colourless oil (0.033 g).

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. extractionextracted with ethyl acetate (3×10 mL)
  3. washThe combined extracts were washed saturated aqueous sodium chloride solution
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customPurification of the residue by column chromatography on silica gel
  7. washeluting with a mixture of ethyl acetate and cyclohexane (0:1 to 4:6 by volume)

Sources & evidence

ORD record
ord-f84b059ec89642fcbc68e46ef12cdc15
Source dataset
uspto-grants-2012_05
Patent number
US08173812B2

Linked notes

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