Formaldehyde → Dimethyl 4-(2,6-dichlorophenyl)-6-(2-phenylethyl)-2-(1-oxo-1-methoxy-2-propen-2-yl)-1,4-dihydropyridine-3,5-dicarboxylate

HRID 343311Notes

Reaction equation

HRID 343311 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH:9]1[C:14]([C:15]([O:17][CH3:18])=[O:16])=[C:13]([CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[NH:12][C:11]([CH2:27][C:28]([O:30][CH3:31])=[O:29])=[C:10]1[C:32]([O:34][CH3:35])=[O:33].[CH3:36]N1CCNCC1.C=O>C(O)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH:9]1[C:14]([C:15]([O:17][CH3:18])=[O:16])=[C:13]([CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[NH:12][C:11]([C:27](=[CH2:36])[C:28](=[O:29])[O:30][CH3:31])=[C:10]1[C:32]([O:34][CH3:35])=[O:33]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 531671-MethylpiperazineHCID 70203360Dimethyl 4-(2,6-dichlorophenyl)-2-methoxycarbonylmethyl-6-(2-phenylethyl)-1,4-dihydropyridine-3,5-dicarboxylate

Product 1

HCID 131721086Dimethyl 4-(2,6-dichlorophenyl)-6-(2-phenylethyl)-2-(1-oxo-1-methoxy-2-propen-2-yl)-1,4-dihydropyridine-3,5-dicarboxylateYield 50.9%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Dimethyl 4-(2,6-dichlorophenyl)-2-methoxycarbonylmethyl-6-[2-(phenyl)ethyl]-1,4-dihydropyridine-3,5-dicarboxylate (588 mg, 1.135 m mol) and N-methylpiperazine (0.132 ml, 1.19 m mol) were dissolved in acetic acid (3 ml) and to the solution was added paraformaldehyde. The mixture was stirred at room temperature overnight. The mixture was concentrated in vacuo and partitioned between CH2Cl2 (50 ml) and aqueous NaHCO3 solution (20 ml). The aqueous layer was extracted with CH2Cl2 (30 ml). The combined organic layer and the extract were washed with brine (10 ml), dried (MgSO4), and concentrated in vacuo to give a yellow oil. This was crystallized from ethyl acetate and isopropyl ether gave a yellow solid (270 mg, 50.9%). Second crop was obtained from the mother liquid (78 mg, 14.7%). 1H NMR (D2O) δ7.35-7.16 (m, 7H), 7-05-6.97 (m, 1H), 6.21 (br.s, 1H), 6.06 (s, 1H), 5.52 (br.s, 1H), 5.43 (br.s, 1H), 3.73 (s, 3H), 3.57 (s, 3H), 3.46 (s, 3H), 3.10-2.80 (m, 4H).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. custompartitioned between CH2Cl2 (50 ml) and aqueous NaHCO3 solution (20 ml)
  3. extractionThe aqueous layer was extracted with CH2Cl2 (30 ml)
  4. washThe combined organic layer and the extract were washed with brine (10 ml)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customto give a yellow oil
  8. customThis was crystallized from ethyl acetate and isopropyl ether

Sources & evidence

ORD record
ord-f6bb277c56ab4a1a90411bd579598096
Source dataset
uspto-grants-1999_01
Patent number
US05861402

Reaction notes

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