Acetic Acid → [1-(4-Chloro-3-ethoxy-benzyl)-piperidin-4-yl]-carbamic acid tert-butyl ester

HRID 2242957Notes

Reaction equation

HRID 2242957 reaction equation
[C:1]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[Cl:15][C:16]1[CH:23]=[CH:22][C:19]([CH:20]=O)=[CH:18][C:17]=1[O:24][CH2:25][CH3:26].C(O)(=O)C.C([BH3-])#N.[Na+]>C(O)C>[C:1]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:13][CH2:12][N:11]([CH2:20][C:19]2[CH:22]=[CH:23][C:16]([Cl:15])=[C:17]([O:24][CH2:25][CH3:26])[CH:18]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 7238334-(N-Boc-amino)piperidineHCID 5003444Sodium cyanoborohydrideHCID 547756424-Chloro-3-ethoxybenzaldehyde2×

Product 1

HCID 67147374[1-(4-Chloro-3-ethoxy-benzyl)-piperidin-4-yl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
100 °C

Procedure

A mixture of piperidin-4-yl-carbamic acid tert-butyl ester (5.0 g, 25.0 mmol, 1.0 equiv), 4-chloro-3-ethoxy-benzaldehyde (5.54 g, 30.0 mmol, 1.2 equiv; intermediate D2, vide infra) and acetic acid (5.7 mL, 6.01 g, 100.0 mmol, 4.0 equiv) in ethanol (25 mL) was heated by microwave irradiation to 100° C. for 5 min. Sodium cyanoborohydride (3.14 g, 50.0 mmol, 2.0 equiv), dissolved in ethanol (10 mL), was added and the reaction mixture heated by microwave irradiation to 100° C. for an additional time period of 10 min. The solvent was removed under reduced pressure and the crude reaction product extracted from a solution of 1 M NaOH (100 mL) with ethyl acetate (3×100 mL). The combined organic phases were dried over MgSO4, concentrated by evaporation under reduced pressure and the crude material purified by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane/ethyl acetate providing 3.91 g (42%) of the title compound. MS (ISP): 369.0 [M+H]+.

Workup

  1. additionwas added
  2. temperaturethe reaction mixture heated by microwave irradiation to 100° C. for an additional time period of 10 min
  3. customThe solvent was removed under reduced pressure
  4. customthe crude reaction product
  5. extractionextracted from a solution of 1 M NaOH (100 mL) with ethyl acetate (3×100 mL)
  6. dry with materialThe combined organic phases were dried over MgSO4
  7. concentrationconcentrated by evaporation under reduced pressure
  8. customthe crude material purified by silica column chromatography
  9. washeluting with a gradient of heptane/ethyl acetate providing 3.91 g (42%) of the title compound

Sources & evidence

ORD record
ord-157185574b2042a3963795a8a62061b1
Source dataset
uspto-grants-2010_03
Patent number
US07674804B2

Reaction notes

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