Ammonium Chloride → 2-(Pyrid-2-yl)-8-isopropyloxyquinoline

HRID 1754092Notes

Reaction equation

HRID 1754092 reaction equation
I[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[C:5]([O:12][CH:13]([CH3:15])[CH3:14])[CH:6]=[CH:7][CH:8]=2)[N:3]=1.[Br-].[N:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[Zn+].[NH4+].[Cl-]>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[N:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[C:5]([O:12][CH:13]([CH3:15])[CH3:14])[CH:6]=[CH:7][CH:8]=2)[N:3]=1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 579393102-Iodo-8-isopropoxyquinolineHCID 178418723HCID 178418723, compound

Product 1

HCID 690492372-(Pyrid-2-yl)-8-isopropyloxyquinoline

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

Reaction of 2-iodo-quinolin-8-ol 8 with 2-bromopropane following the method described in Example 8 gave 2-iodo-8-isopropoxyquinoline 9 in 84% yield. 9: 1H NMR (CDCl3): δ 7.75-7.67 (m, 2 H), 7.45 (dd, J=7.0 and 8.0, 1 H), 7.33 (dd, J=1.2 and 8.0, 1 H), 7.12 (dd, J=1.2 and 7.0, 1 H), 4.80 (m, 1 H), 1.49 (d, J=5.9, 6 H). To a stirred solution of 9 (29 mg, 0.093 mmol) and PdCl2(PPh3)2 (5 mg) in THF (2.5 mL) under an argon atmosphere at RT was added dropwise over 5 min 2-pyridylzinc bromide (0.370 mL of a 0.5 M solution in THF, 0.185 mmol). After 2 h, saturated NH4Cl (5 mL) was added and the mixture extracted with dichloromethane (10 mL×3). The combined extracts were washed with H2O (10 mL) and brine (10 mL), dried (Na2SO4), and concentrated. Subsequent column chromatography on silica (dichloromethane/MeOH, 19:1) gave 2-(pyrid-2-yl)-8-isopropyloxyquinoline as a yellow solid. The isopropyl ether was cleaved according to the procedure of Example 8, to give 2-(Pyrid-2-yl)-8-hydroxyquinoline P1 (22 mg, 89%) (data in Table 5).

Workup

  1. extractionthe mixture extracted with dichloromethane (10 mL×3)
  2. washThe combined extracts were washed with H2O (10 mL) and brine (10 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-5e9a138379e244acb26d3e4d0b43495b
Source dataset
uspto-grants-2015_10
Patent number
US09169211B2

Reaction notes

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