Hydrochloric Acid → N-isopropyl-1-((4-methoxypyridin-3-yl)methyl)piperidin-4-amine

HRID 1181513Notes

Reaction equation

HRID 1181513 reaction equation
C(OC([N:8]([CH:12]1[CH2:17][CH2:16][N:15]([CH2:18][C:19]2[CH:20]=[N:21][CH:22]=[CH:23][C:24]=2[O:25][CH3:26])[CH2:14][CH2:13]1)[CH:9]([CH3:11])[CH3:10])=O)(C)(C)C.Cl>O1CCOCC1>[CH:9]([NH:8][CH:12]1[CH2:13][CH2:14][N:15]([CH2:18][C:19]2[CH:20]=[N:21][CH:22]=[CH:23][C:24]=2[O:25][CH3:26])[CH2:16][CH2:17]1)([CH3:11])[CH3:10]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 674296194-(N-tert-Butoxycarbonyl-N-isopropylamino)-1-(4-methoxypyrid-3-ylmethyl)piperidine

Product 1

HCID 11651846N-isopropyl-1-((4-methoxypyridin-3-yl)methyl)piperidin-4-amineYield 65%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
5 °C

Procedure

A solution of 4-(N-tert-butoxycarbonyl-N-isopropylamino)-1-(4-methoxypyrid-3-ylmethyl)piperidine (17.0 g, 0.047 mol) in dioxane (93 mL) was cooled to 5° C. in ice/water bath. To this solution was added concentrated hydrochloric acid (40 mL) and the resulting mixture was stirred 5° C. for 15 minutes. The ice/water bath was then removed and the reaction mixture was stirred for 12 hours. The reaction mixture was then concentrated in vacuo to dryness, diluted with dichloromethane (100 mL) and 10 N aqueous sodium hydroxide was added slowly (CAUTION: very exothermic) until the pH was 14. The mixture was stirred for 0.5 hours and the organic layer was then separated and the aqueous layer was washed three times with dichloromethane (200 mL). The organic layers were then separated and dried over sodium sulfate (10 g). The sodium sulfate was removed by filtration and the organic layer was concentrated in vacuo to give 7.8 g of the title intermediate as a yellow oil (65% yield; 83% purity by GC).

Workup

  1. customThe ice/water bath was then removed
  2. stirringthe reaction mixture was stirred for 12 hours
  3. concentrationThe reaction mixture was then concentrated in vacuo to dryness
  4. additiondiluted with dichloromethane (100 mL) and 10 N aqueous sodium hydroxide
  5. additionwas added slowly (CAUTION: very exothermic) until the pH was 14
  6. stirringThe mixture was stirred for 0.5 hours
  7. customthe organic layer was then separated
  8. washthe aqueous layer was washed three times with dichloromethane (200 mL)
  9. customThe organic layers were then separated
  10. dry with materialdried over sodium sulfate (10 g)
  11. customThe sodium sulfate was removed by filtration
  12. concentrationthe organic layer was concentrated in vacuo

Sources & evidence

ORD record
ord-0c373cede2b04a45871853a519fc590b
Source dataset
uspto-grants-2007_10
Patent number
US07285564B2

Reaction notes

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