Diethyl Oxalate → Ethyl 3-benzyloxy-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-2-carboxylate

HRID 346486

Reaction equation

HRID 346486 reaction equation
[C:1]([O:8][CH2:9][CH3:10])(=[O:7])[C:2](OCC)=O.[CH2:11]([O:18][CH2:19][C:20]([O:22]CC)=O)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[H-].[Na+].Cl.[NH:28]=[C:29]1[CH2:34][CH2:33][CH2:32][CH2:31][NH:30]1.[O-]CC.[Na+]>O1CCCC1.C(O)C.C(O)(=O)C>[CH2:11]([O:18][C:19]1[C:20](=[O:22])[N:30]2[CH2:31][CH2:32][CH2:33][CH2:34][C:29]2=[N:28][C:2]=1[C:1]([O:8][CH2:9][CH3:10])=[O:7])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

9

Reactant 5

HCID 7268Diethyl OxalateHCID 24758Sodium hydrideHCID 290299Ethyl 2-(benzyloxy)acetateHCID 2723922Sodium ethoxideHCID 178479080HCID 178479080, compound

Product 1

HCID 21080169Ethyl 3-benzyloxy-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-2-carboxylateYield 14%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

Diethyl oxalate (7.66 g, 52.4 mmol) and ethyl benzyloxyacetate (10.2 g, 52.5 mmol) in dry tetrahydrofuran (70 ml) were treated at 22° C. with sodium hydride (2.31 g of a 60% dispersion in mineral oil, 57.7 mmol) and ethanol (40 μl). The tetrahydrofuran was then evaporated under reduced pressure and the residue treated with a mixture of 2-iminopiperidine hydrochloride (7.05 g, 52.2 mmol) in a solution of sodium ethoxide (26.0 mmol, prepared from 0.60 g of sodium) in ethanol (70 ml) and the resulting mixture heated at 60° C. for 4 h. Acetic acid (2 ml) was added and the ethanol was evaporated under reduced pressure. The residue was diluted with ethyl acetate washed successively with saturated sodium bicarbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Chromatography on silica gel (elution toluene/ethyl acetate 1:1) gave 2.37 g (14% yield) of the title ester as white crystals; mp 97–99° C. (ethyl acetate-hexane). 1HNMR 400 MHz (CDCl3) δ (ppm): 1.33 (3H, t, J=7.1 Hz, CH3), 1.92 (2H, m, CH2), 2.0 (2H, m, CH2), 2.97 (2H, t, J=6.8 Hz, CH2), 4.02 (2H, t, J=6.3 Hz, NCH2), 4.36 (2H, q, J=7.1 Hz, OCH2), 5.27 (2H, s, OCH2), 7.3–7.51 (5H, m, aromatics). Anal. Calcd for C18H20N2O4: C, 65.84; H, 6.14; N, 8.53. Found: C 65.72, H 6.33, N 8.41.

Workup

  1. customThe tetrahydrofuran was then evaporated under reduced pressure
  2. customthe ethanol was evaporated under reduced pressure
  3. additionThe residue was diluted with ethyl acetate
  4. washwashed successively with saturated sodium bicarbonate and brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9b16c11e56dc43afa955cb6ec061fcd3
Source dataset
uspto-grants-2007_02
Patent number
US07173022B2

Linked notes

Loading…