Tetrahydrofuran → (R)-3-(methoxyacetylamino)-1-phenylmethylpiperidine

HRID 1614

Reaction equation

HRID 1614 reaction equation
O1CCCC1.[C:6]1([CH2:12][N:13]2[CH2:18][CH2:17][CH2:16][C@@H:15]([NH2:19])[CH2:14]2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C(N(CC)CC)C.[CH3:27][O:28][CH2:29][C:30](Cl)=[O:31]>O.C(Cl)Cl>[CH3:27][O:28][CH2:29][C:30]([NH:19][C@@H:15]1[CH2:16][CH2:17][CH2:18][N:13]([CH2:12][C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:14]1)=[O:31]

Participants

7

Reactant 4

HCID 8028Tetrahydrofuran3×HCID 8471TriethylamineHCID 96623Methoxyacetyl chlorideHCID 854130(3R)-1-benzylpiperidin-3-amine

Product 1

HCID 51728477(R)-3-(methoxyacetylamino)-1-phenylmethylpiperidineYield 97%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a 50 ml anhydrous tetrahydrofuran solution of 5.00 g (26.3 mmol) of (R)-1-phenylmethyl-3-aminopiperidine (Referential example 7) in a 300 ml three-necked flask was added a 50 ml anhydrous tetrahydrofuran solution of 3.20 g (1.2 eg.) of triethylamine, and, to this reaction mixture was added dropwise a 50 ml anhydrous tetrahydrofuran solution of 2.85 g (1.0 eg.) of methoxyacetyl chloride under stirring and cooling with ice. After reacted for 5 hours at room temperature, methylene chloride and small amount of water were added to extract (20 ml×6). The organic layers were combined and dried over anhydrous sodium sulfate. Then, solvent was distilled off under reduced pressure and the residue thus obtained was purified by column chromatography (alumina, ethyl acetate:n-hexane=1:1) to obtain 6.67 g (yield 97 %) of title compound as a pale yellow oil.

Workup

  1. temperaturecooling with ice
  2. customAfter reacted for 5 hours at room temperature
  3. extractionto extract (20 ml×6)
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationThen, solvent was distilled off under reduced pressure
  6. customthe residue thus obtained
  7. customwas purified by column chromatography (alumina, ethyl acetate:n-hexane=1:1)

Sources & evidence

ORD record
ord-44351331f59d49308273d55a1a4782d5
Source dataset
uspto-grants-1998_03
Patent number
US05726188

Linked notes

Loading…