Toluene → 4-[8-(4-Isopropoxy-phenyl)-quinolin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester

HRID 1958455Notes

Reaction equation

HRID 1958455 reaction equation
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:23]3[C:18](=[C:19](Cl)[CH:20]=[CH:21][CH:22]=3)[N:17]=[CH:16][CH:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].[CH:25]([O:28][C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1)([CH3:27])[CH3:26].C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>C(OCC)(=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:23]3[C:18](=[C:19]([C:32]4[CH:33]=[CH:34][C:29]([O:28][CH:25]([CH3:27])[CH3:26])=[CH:30][CH:31]=4)[CH:20]=[CH:21][CH:22]=3)[N:17]=[CH:16][CH:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 36987264-Isopropoxybenzeneboronic acidHCID 574963804-(8-Chloro-quinolin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester

Product 1

HCID 113853494-[8-(4-Isopropoxy-phenyl)-quinolin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

In a 25 mL round-bottomed flask equipped with a reflux condenser and N2 inlet septum was placed a stir bar, 4-(8-chloro-quinolin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester (200 mg, 0.57 mmol), 4-isopropoxyphenylboronic acid (304 mg, 1.7 mmol), 2M sodium carbonate (0.6 mL) and toluene (4 mL). The mixture was degassed for a few minutes. Tetrakis(triphenylphosphine) palladium (98 mg, 0.085 mmol) was added to the above mixture. The reaction mixture was refluxed overnight under N2. The resulting mixture was diluted with ethyl acetate and extracted with H2O. The organic extract was dried and concentrated to give the crude product. The crude product was purified by column chromatography to using 50% EtOAc/Hexane and preparative HPLC to give the desired product. 1H NMR (CDCl3, 400 MHz) δ 1.28 (d, 6H), 1.39 (d, 6H), 2.03 (m, 2H), 2.17 (m, 2H), 3.59 (m, 2H), 3.85 (m, 2H), 4.63 (m, 1H), 4.97 (m, 1%), 5.12 (m, 1H), 7.04 (s, 1H), 7.22 (d, 1H), 7.37 (d, 2H), 7.81 (t, 1H), 7.90 (d, 1H), 8.36 (d, 1H), 9.06 (d, 1H). Exact mass calculated for C27H32N2O4 448.24, found 449.4 (MH+).

Workup

  1. customIn a 25 mL round-bottomed flask equipped with a reflux condenser and N2 inlet septum
  2. customThe mixture was degassed for a few minutes
  3. temperatureThe reaction mixture was refluxed overnight under N2
  4. extractionextracted with H2O
  5. extractionThe organic extract
  6. customwas dried
  7. concentrationconcentrated
  8. customto give the crude product
  9. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-77a0ea52caed4b92893f55e1019b882d
Source dataset
uspto-grants-2013_04
Patent number
US08410119B2

Reaction notes

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