2,3-Dihydroxybutanedioic Acid → N-(2-(2-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)ethoxy)ethyl)-3-pyrrolidineacetic acid methyl ester

HRID 2226764Notes

Reaction equation

HRID 2226764 reaction equation
Cl.[CH:2]1[C:12]2[CH2:11][CH2:10][C:9]3[CH:13]=[CH:14][CH:15]=[CH:16][C:8]=3[N:7]([CH2:17][CH2:18][O:19][CH2:20][CH2:21][N:22]3[CH2:27][CH2:26][CH:25]=[C:24]([C:28]([OH:30])=[O:29])[CH2:23]3)[C:6]=2[CH:5]=[CH:4][CH:3]=1.[C:31](O)(=O)C.N1CCC(CC(OC)=O)C1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].C(O)(=O)C(C(C(O)=O)O)O>CC(CC(C)C)=O.C(OCC)(=O)C.O.C1COCC1.CCCCCCC>[CH3:31][O:30][C:28](=[O:29])[CH2:24][CH:25]1[CH2:26][CH2:27][N:22]([CH2:21][CH2:20][O:19][CH2:18][CH2:17][N:7]2[C:6]3[CH:5]=[CH:4][CH:3]=[CH:2][C:12]=3[CH2:11][CH2:10][C:9]3[CH:13]=[CH:14][CH:15]=[CH:16][C:8]2=3)[CH2:23]1

Participants

11

Reactant 5

HCID 8752,3-Dihydroxybutanedioic AcidHCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 45260614N-(2-(2-(10,11-Dihydro-5H-dibenz[b,f]azepin-5-yl)ethoxy)ethyl)-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochlorideHCID 70009063Methyl 3-pyrrolidineacetate acetate

Product 1

HCID 67710487N-(2-(2-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)ethoxy)ethyl)-3-pyrrolidineacetic acid methyl esterYield 50%

Reagents, catalysts & solvents 5

HCID 962WaterSolvent2×HCID 7909Methyl Isobutyl KetoneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 8900HeptaneSolvent

Procedure

A mixture of 2-(2-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)ethoxy)ethylchloride (1.5 g, 4.9 mmol, prepared as described in Example 15), methyl 3-pyrrolidineacetate acetate (2.0 g, 9.8 mmol), potassium carbonate (2.4 g, 17 mmol) and potassium iodide (0.16 g) in methylisobutyl ketone (30 ml) was heated at reflux temperature for 48 h. The reaction mixture was allowed to cool and water (40 ml) was added. The phases were separated and from the organic phase the solvent was evaporated in vacuo to give an oily residue. This residue was dissolved in a mixture of ethyl acetate (25 ml) and water (25 ml) and pH was adjusted to 4 with a 34% aqueous tartaric acid solution. The phases were separated and the organic phase was discarded. Ethyl acetate (25 ml) was added to the aqueous phase and pH was adjusted to approx. 9 with a 2 M aqueous sodium hydroxide solution. The phases were separated and from the organic phase the solvent was evaporated in vacuo to give an oily residue which was submitted to column chromatography on silica gel (180 ml) using a mixture of THF and n-heptane (1:1) as eluent. Collecting the proper fraction afforded 1.0 g of N-(2-(2 -(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)ethoxy)ethyl)-3-pyrrolidineacetic acid methyl ester as an oil.

Workup

  1. temperaturewas heated
  2. temperatureat reflux temperature for 48 h
  3. temperatureto cool
  4. customThe phases were separated and from the organic phase the solvent
  5. customwas evaporated in vacuo
  6. customto give an oily residue
  7. customThe phases were separated
  8. additionEthyl acetate (25 ml) was added to the aqueous phase and pH
  9. customThe phases were separated and from the organic phase the solvent
  10. customwas evaporated in vacuo
  11. customto give an oily residue which
  12. customCollecting the proper fraction

Sources & evidence

ORD record
ord-c849d4fbaead412f8bf19ee2a55e2945
Source dataset
uspto-grants-1994_09
Patent number
US05348965

Reaction notes

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