1,4-Dioxane → 1,1-Dimethylethyl N-[1-[3-(trifluoromethyl)-2-pyridinyl]-4-piperidinyl]carbamate

HRID 1868100Notes

Reaction equation

HRID 1868100 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].ClC1CC([C:22]([F:25])([F:24])[F:23])CCN1.CC[N:28]([CH:32]([CH3:34])C)[CH:29]([CH3:31])C.O1CCOC[CH2:36]1>C(Cl)Cl.Cl>[F:23][C:22]([F:25])([F:24])[C:34]1[C:32]([N:12]2[CH2:11][CH2:10][CH:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])[CH2:14][CH2:13]2)=[N:28][CH:29]=[CH:31][CH:36]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 7238334-(N-Boc-amino)piperidineHCID 42628809HCID 42628809, compound

Product 1

HCID 591776761,1-Dimethylethyl N-[1-[3-(trifluoromethyl)-2-pyridinyl]-4-piperidinyl]carbamateYield 80%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 4-(tertbutoxycarbonylamino)piperidine (1.0 g, 5.0 mmol), 2-chloro-4-trifluoromethylpiperidine (3.6 g, 20.0 mmol), DIEA (6.0 mL, 30.0 mmol), and dioxane (2.0 mL) was heated in a microwave reactor at 150° C. for 2 h. the mixture was cooled, diluted with CH2Cl2 (50 mL), and poured in 1N HCl (100 mL). The aqueous phase was extracted with CH2Cl2 (2×100 mL). The combined organic extracts were washed with H2O and brine, dried (MgSO4), and concentrated. Purification by SiO2 chromatography afforded the tert-butyl carbamate (1.39 g), a pale yellow oil, in 80% yield.

Workup

  1. temperaturewas cooled
  2. extractionThe aqueous phase was extracted with CH2Cl2 (2×100 mL)
  3. washThe combined organic extracts were washed with H2O and brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customPurification by SiO2 chromatography

Sources & evidence

ORD record
ord-28de6b1c564a427ab363840e594b2320
Source dataset
uspto-grants-2009_12
Patent number
US07632838B2

Reaction notes

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