p-Toluenesulfonic acid → 2-Amino-1,4-dihydro-4-hydroxybenzo[f]quinolin-3(2H)-one

HRID 1926699Notes

Reaction equation

HRID 1926699 reaction equation
[NH2:1][CH:2]([CH2:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[CH:9][CH:8]=1)[C:3](O)=[O:4].C([O:24][N:25]1C2C(=CC=CC=2)[C@H](C)[C@H](NC(=O)OC(C)(C)C)C1=O)C1C=CC=CC=1.C(Cl)Cl.C1(C)C=CC(S(O)(=O)=O)=CC=1>B(Cl)(Cl)Cl>[NH2:1][CH:2]1[CH2:6][C:7]2[C:16]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[CH:10]=[CH:9][C:8]=2[N:25]([OH:24])[C:3]1=[O:4]

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 6344DichloromethaneHCID 995051-NaphthylalanineHCID 69910675HCID 69910675, compound

Product 1

HCID 596271052-Amino-1,4-dihydro-4-hydroxybenzo[f]quinolin-3(2H)-oneYield 10%

Reagents, catalysts & solvents 1

HCID 25135Boron TrichlorideSolvent

Conditions

Temperature
50 °C

Procedure

Benzyl[4-(benzyloxy)-3-oxo-1,2,3,4-tetrahydrobenzo[t]quinolin-2-yl]carbamate (54, prepared from 2-amino-3-(1-naphthyl)propanoic acid according to the general procedure for synthesis of tert-butyl (3S,4S)-1-(benzyloxy)-4-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-3-ylcarbamate (33) in Example 7) (35 mg, 0.077 mmol) was dissolved in a solution of boron trichloride in DCM (1.0 M, 5.00 mL, 5.00 mmol), and the reaction was heated at 50° C. for 1 h. After being quenched with MeOH (10 mL), the reaction was stirred for 15 min, then treated with silica gel impregnated with p-toluenesulfonic acid (0.68 mEq/g, 2 g, 1.36 mmol). After 1.5 hours, the silica was filtered off and rinsed with MeOH; the silica was then slurried with a 2N solution of ammonia in MeOH for 20 minutes, and filtered. The solids were rinsed with MeOH and the combined filtrates were concentrated in vacuo to afford a solid, which was triturated with Et2O to provide the product as a solid (2 mg, 10%). LCMS m/z 229.0 (M+1). 1H NMR (400 MHz, CD3OD) δ 3.07 (dd, J=15, 15 Hz, 1H), 3.82 (dd, J=16, 6.5 Hz, 1H), 4.00 (dd, J=14, 6 Hz, 1H), 7.45 (dd, J=7, 7 Hz, 1H), 7.58 (dd, J=8, 8 Hz, 1H), 7.67 (d, J=9 Hz, 1H), 7.88 (m, 2H), 8.01 (d, J=9 Hz, 1H).

Workup

  1. customAfter being quenched with MeOH (10 mL)
  2. additiontreated with silica gel
  3. waitAfter 1.5 hours
  4. filtrationthe silica was filtered off
  5. washrinsed with MeOH
  6. waitthe silica was then slurried with a 2N solution of ammonia in MeOH for 20 minutes
  7. filtrationfiltered
  8. washThe solids were rinsed with MeOH
  9. concentrationthe combined filtrates were concentrated in vacuo
  10. customto afford a solid, which
  11. customwas triturated with Et2O

Sources & evidence

ORD record
ord-df1dbd63a3c943c7a49228a126000d96
Source dataset
uspto-grants-2012_05
Patent number
US08183238B2

Reaction notes

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