Hydrochloric Acid → 4-Benzoyl-2-(3,4-difluorophenyl)-2-[2-[4-(methoxycarbonylamino)-4-phenylpiperid-1-yl]ethyl]morpholine hydrochloride monohydrate

HRID 1066671Notes

Reaction equation

HRID 1066671 reaction equation
O.[ClH:2].C(N1CCOC(C2C=CC(F)=C(F)C=2)(CCN2CCC(NC(N(C)C)=O)(C3C=CC=CC=3)CC2)C1)(=[O:10])C1C=CC=CC=1.[C:45]([N:53]1[CH2:58][CH2:57][O:56][C:55]([CH2:67][CH2:68]N2CCC(C3C=CC=CC=3)(NC(N(C)C)=O)CC2)([C:59]2[CH:64]=[CH:63][C:62]([F:65])=[C:61]([F:66])[CH:60]=2)[CH2:54]1)(=[O:52])[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1.Cl.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH3:99][O:100][C:101]([NH:103][C:104]1([C:110]2[CH:115]=[CH:114][CH:113]=[CH:112][CH:111]=2)[CH2:109][CH2:108][NH:107][CH2:106][CH2:105]1)=[O:102].C([O-])([O-])=O.[K+].[K+].Cl>CN(C=O)C.C(Cl)Cl.CCOCC.O>[OH2:10].[ClH:2].[C:45]([N:53]1[CH2:58][CH2:57][O:56][C:55]([C:59]2[CH:64]=[CH:63][C:62]([F:65])=[C:61]([F:66])[CH:60]=2)([CH2:67][CH2:68][N:107]2[CH2:106][CH2:105][C:104]([NH:103][C:101]([O:100][CH3:99])=[O:102])([C:110]3[CH:115]=[CH:114][CH:113]=[CH:112][CH:111]=3)[CH2:109][CH2:108]2)[CH2:54]1)(=[O:52])[C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 212005634-(Methoxycarbonylamino)-4-phenylpiperidine p-toluenesulfonateHCID 1317200584-Benzoyl-2-(3,4-difluorophenyl)-2-[2-[4-(N',N'-dimethylureido)-4-phenylpiperid-1-yl]ethyl]morpholine hydrochloride hemihydrate

Product 1

HCID 212006204-Benzoyl-2-(3,4-difluorophenyl)-2-[2-[4-(methoxycarbonylamino)-4-phenylpiperid-1-yl]ethyl]morpholine hydrochloride monohydrateYield 134.2%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 1.2 g of the compound obtained in step C of EXAMPLE 37, 1.3 g of 4-(methoxycarbonylamino)-4-phenylpiperidine p-toluenesulfonate and 1.2 g of K2CO3 in 3 ml of DMF is heated at 80-100° C. for 2 hours. After cooling to RT, the reaction mixture is poured into water and the precipitate formed is wrung and dried under vaccum. The precipitate is chromatographed on silica H using a DCM/MeOH mixture (from 100/1.5; v/v to 100/3; v/v) as the eluent. The product obtained is dissolved in DCM, a saturated solution of hydrochloric acid in ether is added until the pH is 1, and the precipitate formed is wrung to give 0.8 g of the expected product. M.p.=170° C.

Workup

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

Sources & evidence

ORD record
ord-6547b5a0ed0a41ebab97de29e980a4c1
Source dataset
uspto-grants-2001_06
Patent number
US06242637B1

Reaction notes

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