1-(3-Chloro-4-fluorobenzyl)-5,6-dihydropyridin-2(1H)-one → Ethyl 6-(3-chloro-4-fluorobenzyl)-4-hydroxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate

HRID 18007Notes

Reaction equation

HRID 18007 reaction equation
C(O[C:6]1[O:10][C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[N:8][CH:7]=1)CCC.[Cl:16][C:17]1[CH:18]=[C:19]([CH:28]=[CH:29][C:30]=1[F:31])[CH2:20][N:21]1[CH2:26][CH2:25][CH:24]=[CH:23][C:22]1=[O:27]>O>[Cl:16][C:17]1[CH:18]=[C:19]([CH:28]=[CH:29][C:30]=1[F:31])[CH2:20][N:21]1[CH2:26][CH2:25][C:24]2[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[N:8][CH:7]=[C:6]([OH:10])[C:23]=2[C:22]1=[O:27]

Participants

4

Reactant 2

HCID 594556041-(3-Chloro-4-fluorobenzyl)-5,6-dihydropyridin-2(1H)-oneHCID 66996945Ethyl 5-butoxy-1,3-oxazole-2-carboxylate

Product 1

HCID 59455599Ethyl 6-(3-chloro-4-fluorobenzyl)-4-hydroxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
135 °C

Procedure

A mixture of ethyl 5-butoxy-1,3-oxazole-2-carboxylate (248 g, 1.16 mol; Example 1, step 5), 1-(3-chloro-4-fluorobenzyl)-5,6-dihydropyridin-2(1H)-one (199.2 g, 0.83 mol; Example 1, step 2), and deionized water (22.5 mL, 1.25 mol) in a glass lined stainless steel high pressure reactor (with the interstitial space between the liner and the pressure vessel was filled with water) was heated at 135° C. with stirring for 72 hours. The product mixture was cooled in an ice-water bath and the gaseous by-product was carefully vented. The orange solid product was triturated with methyl tert-butyl ether (300 mL) and collected by filtration. The product recrystallized from boiling ethanol-water (˜500 mL, 9:1 v/v), collected by filtration, washed successively with a small quantity of ethanol, methyl tert-butyl ether (300 mL), and heptane (200 mL), and air dried to afford the title compound.

Workup

  1. temperatureThe product mixture was cooled in an ice-water bath
  2. customThe orange solid product was triturated with methyl tert-butyl ether (300 mL)
  3. filtrationcollected by filtration
  4. customThe product recrystallized
  5. filtrationcollected by filtration
  6. washwashed successively with a small quantity of ethanol, methyl tert-butyl ether (300 mL), and heptane (200 mL), and air
  7. customdried

Sources & evidence

ORD record
ord-6b5c5f88993d4e339f1408e011b9d1b3
Source dataset
uspto-grants-2010_06
Patent number
US07741315B2

Reaction notes

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