Lithium Chloride → 6-((Benzyloxy)carbonyl)-2-methyl-4-(p-tolyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carboxylic acid

HRID 470925Notes

Reaction equation

HRID 470925 reaction equation
[CH3:1][C:2]1[C:11]([C:12]([O:14]C)=[O:13])=[C:10]([C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)[C:9]2[CH2:8][N:7]([C:23]([O:25][CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[O:24])[CH2:6][CH2:5][C:4]=2[N:3]=1.[Cl-].[Li+]>CS(C)=O.O>[CH2:26]([O:25][C:23]([N:7]1[CH2:6][CH2:5][C:4]2[N:3]=[C:2]([CH3:1])[C:11]([C:12]([OH:14])=[O:13])=[C:10]([C:16]3[CH:17]=[CH:18][C:19]([CH3:22])=[CH:20][CH:21]=3)[C:9]=2[CH2:8]1)=[O:24])[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

5

Reactant 2

HCID 433294Lithium ChlorideHCID 866921996-benzyl 3-methyl 2-methyl-4-(p-tolyl)-7,8-dihydro-1,6-naphthyridine-3,6(5H)-dicarboxylate2×

Product 1

HCID 866921986-((Benzyloxy)carbonyl)-2-methyl-4-(p-tolyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carboxylic acidYield 15.9%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 6-benzyl 3-methyl 2-methyl-4-(p-tolyl)-7,8-dihydro-1,6-naphthyridine-3,6(5H)-dicarboxylate (intermediate 10) (0.482 g, 1.12 mmol) and lithium chloride (0.475 g, 11.19 mmol) in 2,6-lutadine (10 mL) and DMSO (10.00 mL) was stirred at 130° C. for 2 h. The mixture was cooled to room temperature, diluted with water and extracted with EtOAc to remove unreacted starting material and impurities. The aqueous phase was made acidic with 1N HCl and extracted with EtOAc (2×'s) then CH2Cl2. The organic extracts were combined, dried (Na2SO4), filtered and concentrated to provide 6-((benzyloxy)carbonyl)-2-methyl-4-(p-tolyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carboxylic acid (74.2 mg, 15% yield) as an amber oil. 1H NMR (400 MHz, CDCl3) δ ppm 7.33 (br. s., 4H), 7.24 (d, J=7.83 Hz, 3H), 7.13 (d, J=7.58 Hz, 2H), 5.11 (s, 2H), 4.36 (s, 2H), 3.78 (t, J=5.62 Hz, 2H), 3.30 (br. s., 2H), 2.80 (br. s., 3H), 2.38 (s, 3H). LCMS (M+H) calcd for C25H25N2O4: 417.18. found: 417.4.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionextracted with EtOAc
  3. customto remove unreacted
  4. extractionextracted with EtOAc (2×'s) then CH2Cl2
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-38efcb14c87b4b4fb74d511806e60935
Source dataset
uspto-grants-2014_01
Patent number
US08629276B2

Reaction notes

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