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

HRID 73865Notes

Reaction equation

HRID 73865 reaction equation
[OH-].[Na+].C1(C[O:10][C:11]([C:13]2([NH:19][C:20]([C:22]3[CH:27]=[CH:26][C:25]([CH2:28][N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)=[CH:24][CH:23]=3)=O)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)=[O:12])C=CC=CC=1.Cl.C(N(CC)CC)C.Cl.C(N=C=NCCCN(C)C)C>O1CCCC1.C(Cl)Cl>[N:29]1([CH2:28][C:25]2[CH:24]=[CH:23][C:22]([C:20]3[O:10][C:11](=[O:12])[C:13]4([CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]4)[N:19]=3)=[CH:27][CH:26]=2)[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 576728421-[[[4-(4-Morpholinylmethyl)phenyl]carbonyl]amino]cyclohexanecarboxylic acid phenylmethyl ester

Product 1

HCID 576728122-[4-(4-Morpholinylmethyl)phenyl]-3-oxa-1-azaspiro[4.5]dec-1-en-4-oneYield 84.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

2 ml of 2N aqueous sodium hydroxide solution was added to a solution of 300 mg (0.69 mmol) of 1-[[[4-(4-morpholinylmethyl)phenyl]carbonyl]amino]cyclohexanecarboxylic acid phenylmethyl ester in 2 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. 3 ml of methylene chloride, 698 mg (6.9 mmol) of triethylamine and 264 mg (1.38 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 191 mg (80%) 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-24c82fcb312c4c3494d697a36a20f488
Source dataset
uspto-grants-2014_09
Patent number
US08829209B2

Reaction notes

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