Hydrochloric Acid → 8-(2-Chlorophenyl)-6-methyl-1,8-dihydropyrido [2,1-c][1,4]-oxazine-7,9-dicarboxylic acid 9-ethyl 7-methyl ester

HRID 1253Notes

Reaction equation

HRID 1253 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[Cl:31])[C:7]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[C:8]([CH2:12][O:13][CH2:14][CH:15](OC)OC)[NH:9][C:10]=1[CH3:11])=[O:4].Cl>O1CCCC1>[CH3:1][O:2][C:3]([C:5]1[CH:6]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[Cl:31])[C:7]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[C:8]2[N:9]([C:10]=1[CH3:11])[CH:15]=[CH:14][O:13][CH2:12]2)=[O:4]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 698306344-(2-Chlorophenyl)-2-(2,2-dimethoxy-ethoxymethyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic acid 3-ethyl 5-methyl ester

Product 1

HCID 867521818-(2-Chlorophenyl)-6-methyl-1,8-dihydropyrido [2,1-c][1,4]-oxazine-7,9-dicarboxylic acid 9-ethyl 7-methyl esterYield 65.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(2-chlorophenyl)-2-(2,2-dimethoxy-ethoxymethyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic acid 3-ethyl 5-methyl ester (XX, 9.2 g) in tetrahydrofuran (200 mL) was added 3N hydrochloric acid (40 mL). The mixture was then refluxed for 4 h. On cooling to room temperature, tetrahydrofuran was removed under reduced pressure and the residue taken up in ethyl acetate (200 mL). The organic phase was washed with brine, dried (sodium sulfate), filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (grade 9385, Merck, 230-400 mesh, 60 Å) using a solvent mixture of hexane and ethyl acetate as eluent (90:10; 1L) as eluent to afford the title compound (XXI 5.2 g). 1H-NMR (CDCl3) δ (ppm): 1.22 (t, 3H, J=7.1 Hz), 2.43 (s, 3H), 3.68 (s, 3H), 4.12 (q, 2H, J=7. 1 Hz),4,60(d,1H, J=13.5 Hz), 5.48 (s, 1H), 5.70 (d, 1H, J=13.8 Hz), 6.21 (d, 1H, J=4.7 Hz), 6.30(d, 1H, J=4.6 Hz), 7.07-7.28 (m, 4H); 13C-NMR (CDCl3) δ (ppm): 14.1, 15.7, 36.6, 51.2, 60.6, 63.5, 105.8, 106.7, 107.8, 127.3, 127.8, 129.5, 130.4, 131.8, 132.5 139.2, 142.0, 143.4, 166.4, 168.1; HRMS: calc. for C20H20CIN2O5 389.1030 found 389.1020; Elemental Analysis (%): calc. (found) C 61.62 (61.78), H 5.17 (5.27), N 3.59 (3.51); M.p. 126.0°-126.8° C.; IR (KBr, cm-1): 1693, 1662, 1645, 1581.

Workup

  1. temperatureThe mixture was then refluxed for 4 h
  2. customtetrahydrofuran was removed under reduced pressure
  3. washThe organic phase was washed with brine
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica gel (grade 9385, Merck, 230-400 mesh, 60 Å)
  8. additiona solvent mixture of hexane and ethyl acetate as eluent (90:10; 1L) as eluent

Sources & evidence

ORD record
ord-1b853575abe94e7c8c35c82d1e1ed7b0
Source dataset
uspto-grants-1998_03
Patent number
US05723618

Reaction notes

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