4-Methylmorpholine → 4-(3,5dichlorophenoxy)piperidine Dihydrochloride

HRID 2185483Notes

Reaction equation

HRID 2185483 reaction equation
CN1CCOCC1.[ClH:8].CN(C)CCCN=C=NCC.C(OC(NCC(N[C@@H]1CN(C(OC(C)(C)C)=O)[C@@H](C(O)=O)C1)=O)=O)(C)(C)C.[Cl:47][C:48]1[CH:49]=[C:50]([CH:58]=[C:59]([Cl:61])[CH:60]=1)[O:51][CH:52]1[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]1.ON1C2C=CC=CC=2N=N1>O1CCCC1.CN(C)C=O>[ClH:47].[ClH:8].[Cl:47][C:48]1[CH:49]=[C:50]([CH:58]=[C:59]([Cl:61])[CH:60]=1)[O:51][CH:52]1[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21341552n-Tert-butoxycarbonyl-trans-4-(n-tert-butoxycarbonylglycylamino)-d-prolineHCID 224584124-(3,5-Dichlorophenoxy)piperidine

Product 1

HCID 867581244-(3,5dichlorophenoxy)piperidine DihydrochlorideYield 347.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

N-Methylmorpholine (70 μL) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (114 mg) were added to a solution of trans-4-(N-tert-butoxycarbonylglycylamino)-N-tert-butoxycarbonyl-D-proline (Compound D105 (F), 220 mg), 4-(3,5-dichlorophenoxy)piperidine (154 mg) and 1-hydroxybenzotriazole (85 mg) in tetrahydrofuran (8 mL) and N,N-dimethylformamide (2 mL) at room temperature. After stirring at room temperature for 12 hr, the reaction mixture was partitioned between ethyl acetate and 1 N hydrochloric acid. The organic layer was washed with saturated sodium hydrogen carbonate and brine. After drying over anhydrous sodium sulfate, the organic layer was evaporated in vacuo. The residue was washed with hexane to give the titled compound (347 mg) as a white powder.

Workup

  1. customthe reaction mixture was partitioned between ethyl acetate and 1 N hydrochloric acid
  2. washThe organic layer was washed with saturated sodium hydrogen carbonate and brine
  3. dry with materialAfter drying over anhydrous sodium sulfate
  4. customthe organic layer was evaporated in vacuo
  5. washThe residue was washed with hexane

Sources & evidence

ORD record
ord-e4bd081705494bc1983af18eb476ca84
Source dataset
uspto-grants-2002_06
Patent number
US06399629B1

Reaction notes

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