Ethyl Acetate → n-Methyl-hydroxybenzoquinoline

HRID 1873084Notes

Reaction equation

HRID 1873084 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]3[CH:14]=[CH:13][CH:12]=[CH:11][C:9]3=2)[CH:4]=C[CH:2]=1.COC1C=NC2C(C=1)=CC=C1C=CC=CC=21.C([Li])CCC.CCO[C:39]([CH3:41])=[O:40]>C1COCC1>[CH3:2][N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]3[CH:14]=[CH:13][CH:12]=[CH:11][C:9]3=2)[CH:4]=[CH:41][CH:39]1[OH:40]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 9191Benzo(h)quinolineHCID 111951503-MethoxybenzoquinolineHCID 178418339Butyllithium

Product 1

HCID 67021686n-Methyl-hydroxybenzoquinoline

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Compound 13 was alkylated with Mel according to a general amino group alkylation procedure as follows. The 3-methoxybenzoquinoline derivative (100 mg) 13 was suspended in 5 mL of dry THF and cooled to -5° C. (ice/NaCl). 1.1 equivalents of n-butyl lithium (1 M) was added dropwise, and the reaction was stirred for 1 hour. 3 equivalents of the Mel alkylating agent was added slowly and the reaction was allowed to stir at room temperature for 2 hours. Aqueous work-up using NH4C1 and EtOAc gave a crude alkylated 3-methoxybenzoquinoline intermediate 14. Intermediate 14 was then purified by normal phase flash chromatography employing EtOAc: hexane (1:19) as the mobile phase (1HNMR: CD3Cl d 8.1 (broad d, 1 H, J=8.1 Hz), 7.68(dd, 1 H, J=8.1, 1.8 Hz), 7.34 (m, 2 H), 6.8 (s, 1 H), 3.92 (s, 3 H), 3.21 (m, 2 H), 2.94 (s, 3 H), 2.77 (t, 2H, J=6.6 Hz), 1.92 (m, 2 H)). Subsequent methoxy group deprotection by the general boron tribromide procedure described above in Example 1 resulted in the N-methyl-hydroxybenzoquinoline derivative 15.

Workup

  1. addition3 equivalents of the Mel alkylating agent was added slowly
  2. stirringto stir at room temperature for 2 hours
  3. customgave a crude alkylated 3-methoxybenzoquinoline intermediate 14
  4. customIntermediate 14 was then purified by normal phase flash chromatography

Sources & evidence

ORD record
ord-3ef72489c824454d9de620b18a7adc3c
Source dataset
uspto-grants-2000_08
Patent number
US06111116

Reaction notes

Loading…