Methylenechloride Hexane → 2-Isopropyl-3-hydroxymethyl-4-(4-fluorophenyl)-5,6,7,8-tetrahydro-8,8-dimethylquinoline

HRID 324883Notes

Reaction equation

HRID 324883 reaction equation
[CH:1]([C:4]1[C:13]([C:14](OCC)=[O:15])=[C:12]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[C:11]2[CH2:10][CH2:9][CH2:8][C:7]([CH3:27])([CH3:26])[C:6]=2[N:5]=1)([CH3:3])[CH3:2].[H-].[Al+3].[Li+].[H-].[H-].[H-].C(Cl)Cl.CCCCCC>C1COCC1>[CH:1]([C:4]1[C:13]([CH2:14][OH:15])=[C:12]([C:19]2[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=2)[C:11]2[CH2:10][CH2:9][CH2:8][C:7]([CH3:27])([CH3:26])[C:6]=2[N:5]=1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 21226440Methylenechloride HexaneHCID 21226445Aluminium lithium hydrideHCID 220050562-Isopropyl-3-carboethoxy-4-(4-fluorophenyl)-5,6,7,8-tetrahydro-8,8-dimethylquinoline

Product 1

HCID 220050492-Isopropyl-3-hydroxymethyl-4-(4-fluorophenyl)-5,6,7,8-tetrahydro-8,8-dimethylquinolineYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To the intermediate obtained in Step B (1.32 g, 3.6 mmol) in THF (35 mL) was added lithium aluminum hydride (1 M/THF, 2 eq., 7.2 mL) dropwise. The reaction was refluxed for 1.5 hours and cooled to room temperature. Then the reaction was quenched with water and the THF was evaporated. The residue was partitioned between diethyl ether (150 mL) and water (100 mL). The organic layer was washed with brine (1×100 mL), dried with MgSO4, filtered, and concentrated to afford a solid. Flash chromatography (40% CH2Cl2/hexane) afforded the title compound as a white solid (808 mg, 2.5 mmol, 70%). 1H NMR (300 MHz, CDCl3): δ 7.13 (d, J=7.0 Hz, 4H), 4.36 (d, J=5.5 Hz, 2H), 3.42 (septet, J=6.6 Hz, 1H), 2.24 (t, J=5.5 Hz, 2H), 1.67 (m, 4H), 1.32 (m, 13H). FAB-MS: calculated for (C21H26FNO) 327, found 328 (M+H). mp 146-149° C. Rf=0.2 (50% CH2Cl2/hexane).

Workup

  1. temperatureThe reaction was refluxed for 1.5 hours
  2. customThen the reaction was quenched with water
  3. customthe THF was evaporated
  4. customThe residue was partitioned between diethyl ether (150 mL) and water (100 mL)
  5. washThe organic layer was washed with brine (1×100 mL)
  6. dry with materialdried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto afford a solid

Sources & evidence

ORD record
ord-323622702e754381a1102e9f24019b74
Source dataset
uspto-grants-2001_04
Patent number
US06218431B1

Reaction notes

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