Triethylamine → Benzamide, N-methoxy-N-methyl-4-(2-quinolinylmethoxy)-

HRID 1170259Notes

Reaction equation

HRID 1170259 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][C:13]1[CH:21]=[CH:20][C:16]([C:17]([OH:19])=O)=[CH:15][CH:14]=1.C(N(CC)CC)C.Cl.[CH3:30][O:31][NH:32][CH3:33]>S(Cl)(Cl)=O>[CH3:30][O:31][N:32]([CH3:33])[C:17](=[O:19])[C:16]1[CH:15]=[CH:14][C:13]([O:12][CH2:11][C:2]2[CH:3]=[CH:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[N:1]=2)=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 98385524-(quinolin-2-ylmethoxy)benzoic Acid

Product 1

HCID 44234674Benzamide, N-methoxy-N-methyl-4-(2-quinolinylmethoxy)-

Reagents, catalysts & solvents 1

HCID 24386Thionyl ChlorideSolvent

Procedure

To a solution of 4-(Quinolin-2-ylmethoxy)-benzoic acid (25.98 g, 93 mmole) was added 250 ml of thionyl chloride under N2. The reaction mixture stirred 3 h and the excess thionyl chloride was removed under vacuum. The acid chloride was dissolved in tetrahydrofuran (450 ml) and triethylamine (50 ml, 4 eq.) was slowly added. O,N-dimethyl hydroxylamine hydrochloride (27 g, 3 eq.) was added and the reaction stirred 18 h. The reaction mixture was placed on a rotovap to remove the solvent, partitioned between 1N NaOH and methylene chloride, separated, dried magnesium sulfate, filtered and concentrated. The crude product was filtered through silica gel eluting with 30-70% ethyl acetate/hexane to proved the title compound as a brown oil (26.26 g, 87%); 1H NMR (400 MHz, CDCl3) δ 8.17 (d, J=8.7 Hz, 1H), 8.06 (d, J=8.3 Hz, 1H), 7.81 (d, J=8.3 Hz, 1H), 7.67 (m, 3H), 7.63 (d, J=8.3 Hz, 1H), 7.52 (m, 1H), 7.01 (M, 2H), 5.39 (s, 2H), 3.52 (s, 3H) 3.31 (s, 2H); MS: (M+H m/z=323.2).

Workup

  1. customthe excess thionyl chloride was removed under vacuum
  2. dissolutionThe acid chloride was dissolved in tetrahydrofuran (450 ml)
  3. stirringthe reaction stirred 18 h
  4. customto remove the solvent
  5. custompartitioned between 1N NaOH and methylene chloride
  6. customseparated
  7. filtrationdried magnesium sulfate, filtered
  8. concentrationconcentrated
  9. filtrationThe crude product was filtered through silica gel eluting with 30-70% ethyl acetate/hexane

Sources & evidence

ORD record
ord-e722f289072a457585e2ac00a98c04e9
Source dataset
uspto-grants-2010_11
Patent number
US07825254B2

Reaction notes

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