Sodium Acetate → HCID 69987306, compound

HRID 2257965Notes

Reaction equation

HRID 2257965 reaction equation
[C:1]1(=[O:11])[O:6][C:4](=O)[C@H:3]2[CH:7]=[CH:8][CH2:9][CH2:10][C@@H:2]12.Cl.[NH2:13][CH:14]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[CH:21]=1)[CH2:15][C:16]([O:18][CH3:19])=[O:17].C([O-])(=O)C.[Na+]>C(O)(=O)C>[C:1]1(=[O:11])[N:13]([CH:14]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[CH:21]=2)[CH2:15][C:16]([O:18][CH3:19])=[O:17])[C:4](=[O:6])[C@H:3]2[CH:7]=[CH:8][CH2:9][CH2:10][C@@H:2]12

Participants

5

Reactant 3

HCID 517045Sodium AcetateHCID 16277031Methyl 3-amino-3-(3,4-dimethoxyphenyl)propanoate hydrochlorideHCID 54353527(3aR,7aS)-3a,4,5,7a-Tetrahydro-2-benzofuran-1,3-dione

Product 1

HCID 69987306HCID 69987306, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A stirred mixture of cis-1,2,5,6-tetrahydrophthalic anhydride (0.76 grams, 5.0 mmol), methyl 3-amino-3-(3,4-dimethoxyphenyl)propionate hydrochloride (1.38 grams, 5.0 mmol), and sodium acetate (0.41 grams, 5.0 mmol) in 20 mL of acetic acid under N2 was heated to reflux for 20 hours. The cooled reaction mixture was concentrated in vacuo and the residue diluted with 25 mL of methylene chloride and then 25 mL of saturated sodium bicarbonate was added in portions and the resulting mixture stirred for 30 minutes. The organic phase was separated, dried (sodium sulfate), and concentrated in vacuo to afford the crude product as an oil. The crude product was purified by flash chromatography (silica gel, 1/9 ethyl acetate/hexanes) to afford 0.85 grams (46%) of methyl 3-(cis-1,2,5,6-tetrahydrophthalimido)-3-(3,4-dimethoxyphenyl)-propionate as a solid: mp 100°-101.5° C.; 1H NMR (CDCl3 /TMS) δ 7.00 (m, 2H), 5.83 (m, 2H), 5.77 (dd, J=10.0, 5.9 Hz, 1H, CH), 3.85 (s, 6H, 2 OCH3), 3.62 (dd, J=10.0, 16.4 Hz, 1H), 3.64 (s, 3H, OCH3), 3.10 (dd, J=16.4, 5.9 Hz, 1H), 3.00 (m, 2H), 2.62-2.45 (m, 2H), 2.30-2.22 (m, 2H); 13C NMR (CDCl3 /TMS) δ 180.0, 179.7, 170.3, 148.8, 130.6, 127.6, 127.5, 120.1, 111.0, 110.8, 55.8, 55.8, 51.8, 51.4, 38.8, 35.3, 23.5, 23.4; TLC (1/9 EtOAc/hexanes, UV) Rf =0.34. Anal. Calcd for C20H23NO6. Theory C, 64.33; H, 6.21; N, 3.75. Found C, 64.29; H, 6.19; N, 3.68.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 20 hours
  3. customThe cooled reaction mixture
  4. concentrationwas concentrated in vacuo
  5. additionthe residue diluted with 25 mL of methylene chloride
  6. addition25 mL of saturated sodium bicarbonate was added in portions
  7. customThe organic phase was separated
  8. dry with materialdried (sodium sulfate)
  9. concentrationconcentrated in vacuo
  10. customto afford the crude product as an oil
  11. customThe crude product was purified by flash chromatography (silica gel, 1/9 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-f8dc3d0d08614feca00c844592b7820a
Source dataset
uspto-grants-1997_08
Patent number
US05658940

Reaction notes

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