Hydrochloric Acid → 3-Benzyl-5-(3,4-dichlorophenyl)-5-[3-[4-(N-phenylacetamido)piperid-1-yl]propyl]tetrahydro-2H-1,3-oxazin-2-one hydrochloride

HRID 1601909

Reaction equation

HRID 1601909 reaction equation
[NH:1]([CH:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:14]([N:21]1[CH2:26][C:25]([C:35]2[CH:40]=[CH:39][C:38]([Cl:41])=[C:37]([Cl:42])[CH:36]=2)([CH2:27][CH2:28][CH2:29]OS(C)(=O)=O)[CH2:24][O:23][C:22]1=[O:43])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[I-].[K+].[C:46](OC(=O)C)(=[O:48])[CH3:47].Cl>CN(C=O)C.CCOCC.O>[ClH:41].[CH2:14]([N:21]1[CH2:26][C:25]([C:35]2[CH:40]=[CH:39][C:38]([Cl:41])=[C:37]([Cl:42])[CH:36]=2)([CH2:27][CH2:28][CH2:29][N:11]2[CH2:12][CH2:13][CH:8]([N:1]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[C:46](=[O:48])[CH3:47])[CH2:9][CH2:10]2)[CH2:24][O:23][C:22]1=[O:43])[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 7918Acetic AnhydrideHCID 899824-AnilinopiperidineHCID 158866793-Benzyl-5-(3,4-dichlorophenyl)-5-[3-(methanesulfonyloxy)propyl]tetrahydro-2H-1,3-oxazin-2-one

Product 1

HCID 212006653-Benzyl-5-(3,4-dichlorophenyl)-5-[3-[4-(N-phenylacetamido)piperid-1-yl]propyl]tetrahydro-2H-1,3-oxazin-2-one hydrochloride

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 1.76 g of 4-anilinopiperidine, 2 g of the compound obtained in step C of EXAMPLE 8 and 0.75 g of potassium iodide in 10 ml of DMF is heated at 50° C. for 1 hour 30 minutes. The reaction mixture is poured into water and extracted with AcOEt, the organic phase is washed three times with water and with saturated NaCl solution and dried over MgSO4 and the solvent is evaporated off under vacuum. The residue is chromatographed on silica H using DCM and then a DCM/MeOH mixture (96/4; v/v) as the eluent. The product obtained is taken up with 10 ml of acetic anhydride and the reaction mixture is stirred for 48 hours at RT. It is concentrated under vacuum, the residue is extracted with AcOEt, the organic phase is washed twice with 20% aqueous ammonia solution, twice with water and with saturated NaCl solution and dried over MgSO4 and the solvent is evaporated off under vacuum. The product obtained is taken up with a saturated solution of gaseous HCl in ether and the solvent is evaporated off under vacuum to give 1.4 g of the expected product after crystallization from AcOEt. M.p.=195° C.

Workup

  1. extractionextracted with AcOEt
  2. washthe organic phase is washed three times with water
  3. dry with materialwith saturated NaCl solution and dried over MgSO4
  4. customthe solvent is evaporated off under vacuum
  5. customThe residue is chromatographed on silica H
  6. customThe product obtained
  7. concentrationIt is concentrated under vacuum
  8. extractionthe residue is extracted with AcOEt
  9. washthe organic phase is washed twice with 20% aqueous ammonia solution, twice with water and with saturated NaCl solution
  10. dry with materialdried over MgSO4
  11. customthe solvent is evaporated off under vacuum
  12. customThe product obtained
  13. customthe solvent is evaporated off under vacuum

Sources & evidence

ORD record
ord-b864fed9c59141dc8b7a9ac49afbcafe
Source dataset
uspto-grants-1999_11
Patent number
US05977359

Linked notes

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