Hydrochloric Acid → 1-(Tetrahydro-2H-pyran-4-yl)piperidin-4-amine

HRID 2064055Notes

Reaction equation

HRID 2064055 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([N:7]2[CH2:12][CH2:11][CH:10]([NH:13]C(=O)OC(C)(C)C)[CH2:9][CH2:8]2)[CH2:3][CH2:2]1.Cl.CO>O1CCOCC1>[O:1]1[CH2:2][CH2:3][CH:4]([N:7]2[CH2:12][CH2:11][CH:10]([NH2:13])[CH2:9][CH2:8]2)[CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 45792109tert-butyl N-[1-(oxan-4-yl)piperidin-4-yl]carbamate

Product 1

HCID 225621451-(Tetrahydro-2H-pyran-4-yl)piperidin-4-amineYield 92.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

9.2 g (0.0323 mol, 1 eq) of 1,1-dimethylethyl [1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]carbamate, 65 mL (0.258 mol, 8 eq) of 4 M HCl in dioxane, and enough methanol to achieve dissolution were combined and stirred at ambient temperature overnight. The reaction mixture was then evaporated. Dichloromethane and 1 M NaOH were added. Sodium chloride was then added to saturate the aqueous layer. The aqueous layer was extracted with dichloromethane twice. The organic layers were combined, dried with sodium sulfate, and evaporated to yield 5.5 g (92% yield) of 1-(tetrahydro-2H-pyran-4-yl)-4-piperidinamine as a low melting white solid. 1H-NMR (400 MHz, DMSO-d6): δ 3.86 (m, 2H), 3.24 (m, 2H), 2.77 (m, 2H), 2.46 (m, 1H), 2.35 (m, 1H), 2.25-1.05 (v br s, 2H, NH2), 2.07 (m, 2H), 1.64 (m, 4H), 1.39 (m, 2H), 1.16 (m, 2H); MS (ESI): 185 [M+H]+.

Workup

  1. dissolutiondissolution
  2. customThe reaction mixture was then evaporated
  3. additionDichloromethane and 1 M NaOH were added
  4. additionSodium chloride was then added
  5. concentrationto saturate the aqueous layer
  6. extractionThe aqueous layer was extracted with dichloromethane twice
  7. dry with materialdried with sodium sulfate
  8. customevaporated

Sources & evidence

ORD record
ord-1eef54f9ae414209ba85809480cf3294
Source dataset
uspto-grants-2012_10
Patent number
US08288413B2

Reaction notes

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