Hydrochloric Acid → 2-[4-(4-Morpholinylmethyl)phenyl]-3-oxa-1-azaspiro[4.5]dec-1-en-4-one

HRID 73864Notes

Reaction equation

HRID 73864 reaction equation
[OH-].[Na+].C[O:4][C:5]([C:7]1([NH:13][C:14]([C:16]2[CH:21]=[CH:20][C:19]([CH2:22][N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)=[CH:18][CH:17]=2)=O)[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)=[O:6].Cl.C(N(CC)CC)C.Cl.C(N=C=NCCCN(C)C)C>O1CCCC1.C(Cl)Cl>[N:23]1([CH2:22][C:19]2[CH:18]=[CH:17][C:16]([C:14]3[O:4][C:5](=[O:6])[C:7]4([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]4)[N:13]=3)=[CH:21][CH:20]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 576729171-[[[4-(4-Morpholinylmethyl)phenyl]carbonyl]amino]cyclohexanecarboxylic acid methyl ester

Product 1

HCID 576728122-[4-(4-Morpholinylmethyl)phenyl]-3-oxa-1-azaspiro[4.5]dec-1-en-4-oneYield 67.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

18 ml of 2N aqueous sodium hydroxide solution was added to a solution of 2.07 g (5.7 mmol) of 1-[[[4-(4-morpholinylmethyl)phenyl]carbonyl]amino]cyclohexanecarboxylic acid methyl ester in 18 ml of tetrahydrofuran, and the mixture was heated under reflux overnight. After the reaction solution was neutralized by concentrated hydrochloric acid, the reaction solution was distilled off under reduced pressure. 30 ml of methylene chloride, 1.74 g (17 mmol) of triethylamine and 1.65 g (8.6 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride were added to the residue, and the mixture was stirred for 1 hour. The reaction solution was distilled off under reduced pressure, a saturated aqueous sodium bicarbonate solution was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium bicarbonate solution and dried with anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 1.27 g (60%) of the title compound.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux overnight
  3. distillationthe reaction solution was distilled off under reduced pressure
  4. distillationThe reaction solution was distilled off under reduced pressure
  5. additiona saturated aqueous sodium bicarbonate solution was added
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe organic layer was washed with a saturated aqueous sodium bicarbonate solution
  8. dry with materialdried with anhydrous sodium sulfate
  9. distillationThe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-0a6c3eca43bf43c68ae06a9cb4ec7d28
Source dataset
uspto-grants-2014_09
Patent number
US08829209B2

Reaction notes

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