Hydrochloric Acid → HCID 20164994, compound

HRID 255891Notes

Reaction equation

HRID 255891 reaction equation
[CH:1](NC(C)C)(C)[CH3:2].[C:8]([C:10]1[CH:11]=[C:12]([CH:20]=[CH:21][C:22]=1[N:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1)[C:13]([CH2:15][CH2:16][C:17]([OH:19])=[O:18])=[O:14])#[N:9].[H-].[Na+].C([Li])CCC.C(I)C.Cl>CN(C)C=O.CCCCCC.O>[C:8]([C:10]1[CH:11]=[C:12]([CH:20]=[CH:21][C:22]=1[N:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1)[C:13]([CH:15]([CH2:1][CH3:2])[CH2:16][C:17]([OH:19])=[O:18])=[O:14])#[N:9]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 6340Iodoethane2×HCID 7912DiisopropylamineHCID 24758Sodium hydrideHCID 20164996HCID 20164996, compoundHCID 178418339Butyllithium

Product 1

HCID 20164994HCID 20164994, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8058HexaneSolvent

Procedure

4.9 ml of diisopropylamine and 10 g of 3-(3-cyano-4-morpholinobenzoyl)propionic acid are added to a suspension of 1.7 g of a 50% dispersion of sodium hydride in 35 ml of dimethylformamide and the mixture is heated for 5 minutes to reflux temperature. Then 28.9 ml of a 1.2 molar solution of butyllithium in hexane are added dropwise at -70° C. The reaction mixture is stirred for a further 10 minutes at -30° and then 2.8 ml of ethyl iodide are added at -70° C. The batch is stirred for a further 20 hours at room temperature with the addition of another 5.6 ml of ethyl iodide after the first 3 hours. For working up, water is added and the pH is adjusted to 1 with 120 ml of 1N hydrochloric acid. The aqueous phase is extracted with ether and the ethereal extracts are extracted with 2N sodium carbonate solution. The sodium carbonate extracts are in turn adjusted to pH 1 and then extracted with a 1:1 mixture of ether/ethyl acetate. These extracts are washed with brine, dried over sodium sulfate and concentrated by evaporation, affording 10.5 g of crude 3-(3-cyano-4-morpholinobenzoyl)valeric acid, which is further reacted direct as described above.

Workup

  1. temperaturethe mixture is heated for 5 minutes
  2. temperatureto reflux temperature
  3. extractionThe aqueous phase is extracted with ether
  4. extractionthe ethereal extracts are extracted with 2N sodium carbonate solution
  5. extractionextracted with a 1:1 mixture of ether/ethyl acetate
  6. washThese extracts are washed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-297b3f8a0a4d44dba0ce7b15b5f99fe8
Source dataset
uspto-grants-1987_10
Patent number
US04699908

Reaction notes

Loading…