Water → Tert-Butyl 4-{2-[(1S)-1-(Acetylamino)Ethyl]-4-Chlorophenyl}Piperidine-1-Carboxylate

HRID 644954Notes

Reaction equation

HRID 644954 reaction equation
[C:1](Cl)(=[O:3])[CH3:2].[NH2:5][C@H:6]([C:8]1[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:9]=1[CH:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1)[CH3:7].C(N(CC)CC)C.O>C(Cl)Cl>[C:1]([NH:5][C@H:6]([C:8]1[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:9]=1[CH:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22])[CH2:17][CH2:16]1)[CH3:7])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 68518377Tert-Butyl 4-{2-[(1S)-1-Aminoethyl]-4-Chlorophenyl]Piperidine-1-Carboxylate

Product 1

HCID 11668043Tert-Butyl 4-{2-[(1S)-1-(Acetylamino)Ethyl]-4-Chlorophenyl}Piperidine-1-Carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Acetyl chloride (1.71 mL, 24.0 mmol) was added to a solution crude tert-butyl 4-{2-[(1S)-1-aminoethyl]-4-chlorophenyl}piperidine-1-carboxylate (5.42 g of ˜70% pure material, 11.2 mmol) and triethylamine (6.69 mL, 48.0 mmol) in methylene chloride at approximately 0° C. After 2 h, the reaction mixture was poured into water and extracted three times with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel (gradient elution; 35-50% ethyl-acetate/hexanes as eluent) provided tert-butyl 4-{2-[(1S)-1-(acetylamino)ethyl]-4-chlorophenyl}piperidine-1-carboxylate as a pale yellow foam. If desired, traces of the minor R-enantiomer could be removed using preparative chiral high pressure liquid chromatography on CHIRALPAK AD Phase (7.5% ethanol/heptanes as eluent) to give in order of elution: R-enantiomer as a colorless solid followed by the S-enantiomer as a colorless solid.

Workup

  1. extractionextracted three times with ethyl acetate
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customPurification of the crude residue by flash chromatography on silica gel (gradient elution; 35-50% ethyl-acetate/hexanes as eluent)

Sources & evidence

ORD record
ord-be0aab309d164dbc88b5497042c1cc93
Source dataset
uspto-grants-2010_04
Patent number
US07700778B2

Reaction notes

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