Ammonium Chloride → 6-(2-Hydroxyphenyl)-5-[(pyrrolidin-1-yl)carbonyl]-2,2,4-trimethyl-1,2-dihydroquinoline

HRID 909319Notes

Reaction equation

HRID 909319 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.C([Li])CCC.[CH3:11][C:12]1([CH3:32])[CH:29]=[C:28]([CH3:30])[C:27]2[C:14](=[CH:15][CH:16]=[C:17]3[C:26]=2[C:25](=[O:31])[O:24][C:23]2[C:18]3=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:13]1.[NH4+].[Cl-]>O1CCCC1.C(OCC)(=O)C.CCCCCC>[OH:24][C:23]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[C:17]1[C:26]([C:25]([N:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)=[O:31])=[C:27]2[C:14](=[CH:15][CH:16]=1)[NH:13][C:12]([CH3:11])([CH3:32])[CH:29]=[C:28]2[CH3:30]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 31268PyrrolidineHCID 104937872,2,4-Trimethyl-1,2-dihydro-6-oxa-1-azachrysen-5-oneHCID 178418339Butyllithium

Product 1

HCID 580269346-(2-Hydroxyphenyl)-5-[(pyrrolidin-1-yl)carbonyl]-2,2,4-trimethyl-1,2-dihydroquinolineYield 82%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Pyrrolidine (135 μL, 1.62 mmol) was dissolved in anhydrous tetrahydrofuran (1 mL), and 1.6 M hexane solution of n-butyl litium was added dropwise thereto at 0° C. After the reaction mixture was stirred at same temperature for 30 minutes, an anhydrous tetrahydrofuran solution (3 mL) of 2,2,4-trimethyl-1,2-dihydro-6-oxa-1-azachrysen-5-one (Reference Compound No. 1-1, 80 mg, 0.27 mmol) was dropped and then the reaction mixture was stirred for 30 minutes more. After the saturated aqueous NH4Cl solution (5 mL) was added to the reaction mixture, the reaction mixture was diluted with ethyl acetate (100 mL). The whole was washed with water (100 mL) and saturated brine (50 mL) successively, dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give the titled compound (80.2 mg) as a pale yellow solid. (Yield 82%)

Workup

  1. customat 0° C
  2. addition1-1, 80 mg, 0.27 mmol) was dropped
  3. stirringthe reaction mixture was stirred for 30 minutes more
  4. washThe whole was washed with water (100 mL) and saturated brine (50 mL) successively
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was removed under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-c8c296d2f6b34849bc792e0ffda64752
Source dataset
uspto-grants-2011_09
Patent number
US08017775B2

Reaction notes

Loading…