Carbamate → 2-(Pyridin-4-yl)-2,8-diazaspiro[4.5]decane

HRID 1694288Notes

Reaction equation

HRID 1694288 reaction equation
[CH2:1]1[C:5]2([CH2:10][CH2:9][N:8](C(OC(C)(C)C)=O)[CH2:7][CH2:6]2)[CH2:4][CH2:3][NH:2]1.Cl.Cl[C:20]1[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=1.C(=O)([O-])N.Cl>C(O)(C)C.CO.O1CCOCC1>[N:23]1[CH:24]=[CH:25][C:20]([N:2]2[CH2:3][CH2:4][C:5]3([CH2:6][CH2:7][NH:8][CH2:9][CH2:10]3)[CH2:1]2)=[CH:21][CH:22]=1

Participants

8

Reactant 4

HCID 276CarbamateHCID 313Hydrochloric AcidHCID 818524-Chloropyridine hydrochlorideHCID 23282900tert-Butyl 2,8-diazaspiro(4.5)decane-8-carboxylate

Product 1

HCID 590473022-(Pyridin-4-yl)-2,8-diazaspiro[4.5]decane

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3776IsopropanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

The reaction was performed under an N2 atmosphere. tert-Butyl 2,8-diazaspiro[4.5]decane-8-carboxylate (869 mg, 3.62 mmol), 4-chloropyridine hydrochloride (1.08 g, 7.20 mmol) and TEA (2.5 ml, 18 mmol) were suspended in isopropanol (10 ml). The mixture was heated to 80° C. and stirred overnight at 80° C. Then the solvent was removed in a rotary evaporator. The residue was taken up in DCM and concentrated to small volume again. This process was repeated twice more. The crude product was purified by column chromatography (silica gel, DCM/7M NH3 in MeOH, 98:2). The product obtained still contained impurities and was used in the next stage in that condition. 2. The reaction was performed under an N2 atmosphere. The carbamate (1.034 g, max. 3.26 mmol) was dissolved in MeOH (5 ml) and mixed with 4 M HCl in dioxane (5 ml). The reaction batch was stirred for 2 h at RT. Then the solvent was removed. The crude product was purified by column chromatography (silica gel, DCM/7M NH3 in MeOH, 98:2→95:5→9:1). Yield: 455 mg, 58% over 2 stages.

Workup

  1. customThen the solvent was removed in a rotary evaporator
  2. concentrationconcentrated to small volume again
  3. customThe crude product was purified by column chromatography (silica gel, DCM/7M NH3 in MeOH, 98:2)
  4. customThe product obtained still contained impurities
  5. stirringThe reaction batch was stirred for 2 h at RT
  6. customThen the solvent was removed
  7. customThe crude product was purified by column chromatography (silica gel, DCM/7M NH3 in MeOH, 98:2→95:5→9:1)

Sources & evidence

ORD record
ord-ffed1c54e85d4926b40bce167840d237
Source dataset
uspto-grants-2012_04
Patent number
US08158628B2

Reaction notes

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