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

HRID 29089Notes

Reaction equation

HRID 29089 reaction equation
COCCO[AlH2-]OCCOC.[Na+].[F:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[C:29]3[CH2:28][CH2:27][C:26](=O)[NH:25][C:24]=3[N:23]=[C:22]([CH:31]([CH3:33])[CH3:32])[C:21]=2[C:34]([O:36][CH3:37])=[O:35])=[CH:16][CH:15]=1>C1(C)C=CC=CC=1.C1COCC1>[F:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[C:29]3[CH2:28][CH2:27][CH2:26][NH:25][C:24]=3[N:23]=[C:22]([CH:31]([CH3:32])[CH3:33])[C:21]=2[C:34]([O:36][CH3:37])=[O:35])=[CH:16][CH:15]=1

Participants

5

Reactant 2

HCID 16684438Red-AlHCID 59788802Methyl 4-(4-fluorophenyl)-2-isopropyl-7-oxo-5,6,7,8-tetrahydro-[1,8]naphthyridine-3-carboxylate

Product 1

HCID 11232707Methyl 4-(4-fluorophenyl)-2-isopropyl-5,6,7,8-tetrahydro-[1,8]naphthyridine-3-carboxylateYield 92.1%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

A solution of Red-Al (185 mL, 0.613 mol, 65 weight % in toluene) in anhydrous toluene (250 mL) was cooled to 5° C. A solution of Part B methyl 4-(4-fluorophenyl)-2-isopropyl-7-oxo-5,6,7,8-tetrahydro-[1,8]naphthyridine-3-carboxylate (100. g, 0.292 mol) in anhydrous THF (500 mL) was added over 30 min. The reaction mixture was stirred at 5° C. for 3 h. The reaction was quenched by adding a solution of potassium sodium tartrate (10%, 200 mL) slowly. After toluene (100 mL) was added, the two phases were separated. The organic phase was washed with NaH2PO4 (5%, 200 mL), followed by H2O (200 m]L), and brine (200 m]L), dried over MgSO4, and filtered. The solvent was removed under reduced pressure and the obtained solid dried at 40° C. under vacuum to provide 88.27 g (92% yield) of methyl 4-(4-fluorophenyl)-2-isopropyl-5,6,7,8-tetrahydro-[1,8]naphthyridine-3-carboxylate as an off-white solid: mp 168-170° C.; 1H NMR (400 MHz, CDCl3) δ 1.23 (d, J=7.0 Hz, 6H), 1.79 (m, 2H), 2.37 (t, J=6.4 Hz, 2H), 2.99 (m, 1H), 3.39 (m, 2H), 3.40 (s, 3H), 5.07 (s, 1H), 7.03-7.16 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 169.5, 162.9, 160.4, 155.7, 146.1, 133.8, 129.9, 117.9, 115.1, 114.9, 110.6, 52.0, 41.9, 33.4, 25.3, 23.0, 22.0; HRMS calcd for C19H22FN2O2 (M+1) 329.1665, found 329.1666.

Workup

  1. customThe reaction was quenched
  2. additionby adding a solution of potassium sodium tartrate (10%, 200 mL) slowly
  3. additionAfter toluene (100 mL) was added
  4. customthe two phases were separated
  5. washThe organic phase was washed with NaH2PO4 (5%, 200 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customThe solvent was removed under reduced pressure
  9. customthe obtained solid dried at 40° C. under vacuum

Sources & evidence

ORD record
ord-3abe382427714dbc979fabd99a4887b8
Source dataset
uspto-grants-2008_09
Patent number
US07420059B2

Reaction notes

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