Phenylacetic Acid → 4-Acetamido-4-phenyl-1-[2-[1-(3,4-dichlorophenyl)-2-(N-methyl-N-benzylcarbonylamino)ethoxy]ethyl]piperidine hydrochloride hemihydrate

HRID 1843

Reaction equation

HRID 1843 reaction equation
F[P-](F)(F)(F)(F)F.N1([O:17][P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.Cl.Cl.[C:30]([NH:33][C:34]1([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[CH2:39][CH2:38][N:37]([CH2:40][CH2:41][O:42][CH:43]([C:47]2[CH:52]=[CH:51][C:50]([Cl:53])=[C:49]([Cl:54])[CH:48]=2)[CH2:44][NH:45][CH3:46])[CH2:36][CH2:35]1)(=[O:32])[CH3:31].[C:61]1([CH2:67][C:68]([OH:70])=[O:69])[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1.CC[Cl:73]>C(Cl)Cl.C(N(CC)CC)C>[OH2:17].[ClH:53].[C:30]([NH:33][C:34]1([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[CH2:35][CH2:36][N:37]([CH2:40][CH2:41][O:42][CH:43]([C:47]2[CH:52]=[CH:51][C:50]([Cl:53])=[C:49]([Cl:54])[CH:48]=2)[CH2:44][N:45]([CH3:46])[C:68]([CH2:67][C:61]2[CH:62]=[CH:63][CH:64]=[CH:65][CH:66]=2)=[O:70])[CH2:38][CH2:39]1)(=[O:32])[CH3:31].[C:30]([NH:33][C:34]1([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[CH2:35][CH2:36][N:37]([CH2:40][CH2:41][O:42][CH:43]([C:47]2[CH:52]=[CH:51][C:50]([Cl:53])=[C:49]([Cl:54])[CH:48]=2)[CH2:44][N:45]([C:68]([CH2:67][C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)=[O:69])[CH3:46])[CH2:38][CH2:39]1)(=[O:32])[CH3:31].[ClH:73]

Participants

7

Reactant 4

HCID 999Phenylacetic AcidHCID 6337ChloroethaneHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 196925004-Acetamido-4-phenyl-1-[2-[1-(3,4-dichlorophenyl)-2-(N-methylamino)ethoxy]ethyl]piperidine dihydrochloride

Product 1

HCID 1317205624-Acetamido-4-phenyl-1-[2-[1-(3,4-dichlorophenyl)-2-(N-methyl-N-benzylcarbonylamino)ethoxy]ethyl]piperidine hydrochloride hemihydrate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

0.46 ml of triethylamine and then 0.5 g of BOP are added to a mixture of 0.5 g of the compound obtained in EXAMPLE 11, step B), 0.127 g of phenylacetic acid and 10 ml of DCM. The resulting mixture is concentrated under vacuum and the residue is taken up with AcOEt, washed with water, with 1N NaOH solution and with saturated NaCl solution, dried over MgSO4 and concentrated under vacuum. The residue is chromatographed on silica gel H using DCM and then a DCM/MeOH mixture (94/6; v/v) as the eluent. The product obtained is taken up with DCM, acidified to pH 1 by the addition of hydrochloric ether and concentrated under vacuum to give 0.42 g of the expected hydrochloride after crystallization from iso ether. M.p.=125° C.

Workup

  1. concentrationThe resulting mixture is concentrated under vacuum
  2. washwashed with water, with 1N NaOH solution and with saturated NaCl solution
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under vacuum
  5. customThe residue is chromatographed on silica gel H
  6. customThe product obtained
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-b505007df247456aa881670aca334437
Source dataset
uspto-grants-1998_03
Patent number
US05726313

Linked notes

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