Ethyl Acetate → Methyl 4-(4-fluorophenyl)-2-isopropyl-8-methanesulfonyl-5,6,7,8-tetrahydro-[1,8]naphthyridine-3-carboxylate

HRID 29090

Reaction equation

HRID 29090 reaction equation
[O:1](S(C)(=O)=O)[S:2]([CH3:5])(=O)=[O:3].[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[C:26]3[CH2:25][CH2:24][CH2:23][NH:22][C:21]=3[N:20]=[C:19]([CH:27]([CH3:29])[CH3:28])[C:18]=2[C:30]([O:32][CH3:33])=[O:31])=[CH:13][CH:12]=1.N1C=C(C)C=C(C)C=1.C(OCC)(=O)C>C(Cl)Cl.C1(C)C=CC=CC=1.O>[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[C:26]3[CH2:25][CH2:24][CH2:23][N:22]([S:2]([CH3:5])(=[O:3])=[O:1])[C:21]=3[N:20]=[C:19]([CH:27]([CH3:28])[CH3:29])[C:18]=2[C:30]([O:32][CH3:33])=[O:31])=[CH:13][CH:12]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 115653,5-DimethylpyridineHCID 81560Methanesulfonic anhydrideHCID 11232707Methyl 4-(4-fluorophenyl)-2-isopropyl-5,6,7,8-tetrahydro-[1,8]naphthyridine-3-carboxylate

Product 1

HCID 11407102Methyl 4-(4-fluorophenyl)-2-isopropyl-8-methanesulfonyl-5,6,7,8-tetrahydro-[1,8]naphthyridine-3-carboxylateYield 86.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (MeSO2)2O (15.9 g, 0.091 mol) in anhydrous CH2Cl2 (50 mL) was added to a solution of Part C methyl 4-(4-fluorophenyl)-2-isopropyl-5,6,7,8-tetrahydro-[1,8]naphthyridine-3-carboxylate (10. g, 0.030 mol) and 3,5-lutidine (20.9 mL, 0.182 mol) in anhydrous toluene (100 mL) at room temperature. The reaction mixture was stirred at room temperature for 3 days. Ethyl acetate (200 mL) and H2O (50 mL) were added, and the resulting two phases were separated. The organic phase was washed with aqueous NaHCO3 (5%, 50 mL), followed by half-saturated brine (50 mL). The solvent was removed under reduced pressure to afford a yellowish oil which solidified slowly. The crude material was recrystallized from i-PrOH/H2O (85:15, 45 mL) to afford 10.5 g (85% yield) of methyl 4-(4-fluorophenyl)-2-isopropyl-8-methanesulfonyl-5,6,7,8-tetrahydro-[1,8]naphthyridine-3-carboxylate as a off-white solid.

Workup

  1. customthe resulting two phases were separated
  2. washThe organic phase was washed with aqueous NaHCO3 (5%, 50 mL)
  3. customThe solvent was removed under reduced pressure
  4. customto afford a yellowish oil which
  5. customThe crude material was recrystallized from i-PrOH/H2O (85:15, 45 mL)

Sources & evidence

ORD record
ord-f1e16f2f645848c08392fcd476819a3b
Source dataset
uspto-grants-2008_09
Patent number
US07420059B2

Linked notes

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