Hydrochloric Acid → 4-Benzyl-6-(3,4-dichlorophenyl)-6-[2-[4-phenyl-4-(pyrrolidin-1-ylcarbonylamino)piperid-1-yl]ethyl]morpholin-3-one hydrochloride monohydrate

HRID 1066668Notes

Reaction equation

HRID 1066668 reaction equation
O.Cl.C(N1CC(C2C=CC([Cl:37])=C(Cl)C=2)(CCN2CCC(O)(C3C=CC=CC=3)CC2)[O:13]CC1=O)C1C=CC=CC=1.[CH2:40]([N:47]1[CH2:52][C:51]([CH2:61][CH2:62][N:63]2[CH2:68][CH2:67][C:66]([C:70]3[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=3)(O)[CH2:65][CH2:64]2)([C:53]2[CH:58]=[CH:57][C:56]([Cl:59])=[C:55]([Cl:60])[CH:54]=2)[O:50][CH2:49][C:48]1=[O:76])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.Cl.C1(S(O)(=O)=O)C=CC=CC=1.C1(C2([NH:100][C:101]([N:103]3[CH2:107][CH2:106][CH2:105][CH2:104]3)=[O:102])CCNCC2)C=CC=CC=1.C([O-])([O-])=O.[K+].[K+].Cl>CN(C=O)C.C(Cl)Cl.CCOCC.O>[OH2:13].[ClH:37].[CH2:40]([N:47]1[CH2:52][C:51]([C:53]2[CH:58]=[CH:57][C:56]([Cl:59])=[C:55]([Cl:60])[CH:54]=2)([CH2:61][CH2:62][N:63]2[CH2:68][CH2:67][C:66]([C:70]3[CH:71]=[CH:72][CH:73]=[CH:74][CH:75]=3)([NH:100][C:101]([N:103]3[CH2:107][CH2:106][CH2:105][CH2:104]3)=[O:102])[CH2:65][CH2:64]2)[O:50][CH2:49][C:48]1=[O:76])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 212004754-Phenyl-4-(pyrrolidin-1-ylcarbonylamino)piperidine benzenesulfonateHCID 1317226224-Benzyl-6-(3,4-dichlorophenyl)-6-[2-(4-hydroxy-4-phenylpiperid-1-yl)ethyl]morpholin-3-one hydrochloride hemihydrate

Product 1

HCID 212005004-Benzyl-6-(3,4-dichlorophenyl)-6-[2-[4-phenyl-4-(pyrrolidin-1-ylcarbonylamino)piperid-1-yl]ethyl]morpholin-3-one hydrochloride monohydrateYield 83.2%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 1.1 g of the compound obtained in step B of EXAMPLE 14, 1.2 g of 4-phenyl-4-(pyrrolidin-1-ylcarbonylamino)piperidine benzenesulfonate and 0.95 g of K2CO3 in 3 ml of DMF is heated at 80-100° C. for 3 hours. After cooling to RT, the reaction mixture is poured into water and the precipitate formed is wrung, washed with water and dried under vaccum. The precipitate is chromatographed on silica H using a DCM/MeOH mixture (from 100/2; v/v to 100/3; v/v) as the eluent. The product obtained is dissolved in the minimum amount of DCM and acidified to pH 1 by the addition of a saturated solution of gaseous HCl in ether and the precipitate formed is wrung to give 0.54 g of the expected product. M.p.=158-160° C.

Workup

  1. temperatureAfter cooling to RT
  2. customthe precipitate formed
  3. washwashed with water
  4. customdried under vaccum
  5. customThe precipitate is chromatographed on silica H
  6. customThe product obtained
  7. customthe precipitate formed

Sources & evidence

ORD record
ord-065264adeaa64e018ec4a89e2bc3c2e7
Source dataset
uspto-grants-2001_06
Patent number
US06242637B1

Reaction notes

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