Formaldehyde → HCID 67516649, compound

HRID 61394Notes

Reaction equation

HRID 61394 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH:9]([NH:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:10]([O:12][CH3:13])=[O:11])=[CH:4][CH:3]=1.[CH2:20]=O>C(O)(=O)C.S(=O)(=O)(O)O.O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:5]([CH2:8][CH:9]([C:10]([O:12][CH3:13])=[O:11])[N:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:20]2)=[CH:6][CH:7]=1

Participants

6

Reactant 2

HCID 712FormaldehydeHCID 67513717Methyl 3-(4-chlorophenyl)-2-(ethoxycarbonylamino)propanoate

Product 1

HCID 67516649HCID 67516649, compoundYield 59.3%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 1118Sulfuric AcidSolvent

Procedure

A mixture of methyl 3-(4-chlorophenyl)-2-(ethoxycarbonylamino)propanoate (3.55 g, 12.4 mmol) in acetic acid (12 mL) and sulfuric acid (4 mL) was treated with paraformaldehyde (0.392 g, 13.0 mmol). After stirring at room temperature overnight, the mixture was added to ice (50-60 g), diluted with water (30 mL) and extracted with ethyl acetate (3ט50 mL). The combined organic phase was washed with saturated aqueous sodium chloride (25 mL), dried over MgSO4 and concentrated. Purification by silica gel chromatography (90 g column, 25-50% ethyl acetate in hexanes) gave 2-ethyl 3-methyl 7-chloro-3,4-dihydroisoquinoline-2,3(1H)-dicarboxylate (2.19 g, 59%) as a clear, viscous oil. 1H NMR (CDCl3, 400 MHz) δ 7.12 (m, 3 H), 5.20 (m, ˜0.6 H), 4.98 (m, ˜0.4 H), 4.76 (m, 1 H), 4.53 (m, 1H), 4.25 (m, 2 H), 3.65 (s, 3 H), 3.20 (m, 2 H), 1.35 (t, J=7 Hz, ˜1.8 H), 1.28 (t, J=7 Hz, ˜1.2 H) (mixture of rotamers). ESI+ MS found for C14H16ClNO4 m/z 298.0 (M+H, weak).

Workup

  1. extractionextracted with ethyl acetate (3ט50 mL)
  2. washThe combined organic phase was washed with saturated aqueous sodium chloride (25 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customPurification by silica gel chromatography (90 g column, 25-50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-4574722350e24a27a4c57a0c46b619ef
Source dataset
uspto-grants-2016_09
Patent number
US09440995B2

Reaction notes

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