1-Chloroethyl chloroformate → HCID 70162253, compound

HRID 1251081Notes

Reaction equation

HRID 1251081 reaction equation
C([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15](=[O:44])/[CH:16]=[C:17]2\[C:18]([F:43])([F:42])[CH2:19][CH2:20][N:21]([C:28]([C:30]3[S:34][C:33]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)=[N:32][C:31]=3[CH3:41])=[O:29])[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]\2=3)[CH2:10][CH2:9]1)C1C=CC=CC=1.[Cl:45]C(OC(Cl)C)=O>ClCCl>[ClH:45].[F:43][C:18]1([F:42])[CH2:19][CH2:20][N:21]([C:28]([C:30]2[S:34][C:33]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[N:32][C:31]=2[CH3:41])=[O:29])[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2/[C:17]/1=[CH:16]/[C:15]([NH:14][CH:11]1[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1)=[O:44]

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 70161727HCID 70161727, compound

Product 1

HCID 70162253HCID 70162253, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 500 mg of (Z)-N-(1-benzyl-4-piperidyl)-[4,4-difluoro-1-(4-methyl-2-phenylthiazole-5-carbonyl)-2,3,4,5-tetrahydro-1H-1-benzoazepin-5-ylidene]-acetamide in 15 ml of dichloromethane was added 88 μl of 1-chloroethyl chloroformate, and the mixture was stirred for 3.5 hours with heating under refluxing. The solvent was evaporated, and 20 ml of methanol was added to the residue, followed by stirring at 50° C. for two hours. After this was cooled down to room temperature, a saturated aqueous solution of sodium bicarbonate was added thereto, followed by extracting with ethyl acetate. The organic layer was washed with a saturated aqueous solution of NaCl and dried over anhydrous magnesium sulfate, and the solvent was evaporated. The residue was purified by silica gel column chromatography (eluting with methanol-aqueous ammonia). After making into a hydrochloride using a 4N HCl/ethyl acetate solution, the salt was collected by filtration and washed with ethyl acetate to give 273 mg of (Z)-[4,4-difluoro-1-(4-methyl-2-phenylthiazole-5-carbonyl)-2,3,4,5-tetrahydro-1H-1-benzoazepin-5-ylidene]-N-(4-piperidyl)acetamide monohydrochloride as a colorless powder.

Workup

  1. temperaturewith heating
  2. temperatureunder refluxing
  3. customThe solvent was evaporated
  4. addition20 ml of methanol was added to the residue
  5. stirringby stirring at 50° C. for two hours
  6. additiona saturated aqueous solution of sodium bicarbonate was added
  7. extractionby extracting with ethyl acetate
  8. washThe organic layer was washed with a saturated aqueous solution of NaCl
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customthe solvent was evaporated
  11. customThe residue was purified by silica gel column chromatography (eluting with methanol-aqueous ammonia)
  12. filtrationthe salt was collected by filtration
  13. washwashed with ethyl acetate

Sources & evidence

ORD record
ord-9903aa4b01fe4fb88619ea7b3dcb88f3
Source dataset
uspto-grants-2002_01
Patent number
US06340678B1

Reaction notes

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