1,2-Dichloroethane → [1-(2-Phenyl-cyclopropanecarbonyl)-piperidin-4-ylmethyl]-carbamic acid tert-butyl ester

HRID 1827244Notes

Reaction equation

HRID 1827244 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:3][CH2:2]1.[C:16]1([C@@H:22]2[CH2:24][C@H:23]2[C:25](O)=[O:26])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.C(OCC)(=O)C>[C:11]([O:10][C:9](=[O:15])[NH:8][CH2:7][CH:4]1[CH2:5][CH2:6][N:1]([C:25]([CH:23]2[CH2:24][CH:22]2[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:26])[CH2:2][CH2:3]1)([CH3:12])([CH3:14])[CH3:13]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 237413trans-2-Phenylcyclopropanecarboxylic acidHCID 723429Tert-butyl (piperidin-4-ylmethyl)carbamate

Product 1

HCID 23577319[1-(2-Phenyl-cyclopropanecarbonyl)-piperidin-4-ylmethyl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of tert-butyl piperidin-4-ylmethylcarbamate (Epsilon, 0.80 g, 3.73 mmol), (1R,2R)-2-phenylcyclopropanecarboxylic acid (T. Riley eta al, J. Med. Chem., 15, 1187, 1972) (0.61 g, 3.73 mmol), EDC (1.07 g, 5.60 mmol) and HOBt (0.76 g, 5.60 mmol) in DMF (10 mL) was stirred at RT for 2 h. The reaction mixture was diluted with ethyl acetate (200 mL), washed with aq. sat. NaHCO3 (50 mL), water (5×50 mL), brine (50 mL), dried over Na2SO4, filtered and concentrated. The residue was chromatographed on silica gel 60 (90 g), eluting with 10:1–10:89–80 CH2Cl2:2-propanol:hexane to give the title compound. (1.22 g, 91.0%). M.S. (M+1): 359.

Workup

  1. washwashed with aq. sat. NaHCO3 (50 mL), water (5×50 mL), brine (50 mL)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was chromatographed on silica gel 60 (90 g)
  6. washeluting with 10:1–10:89–80 CH2Cl2

Sources & evidence

ORD record
ord-85365e70addd4c0c8e7246427abcab01
Source dataset
uspto-grants-2006_05
Patent number
US07053089B2

Reaction notes

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