Hydrochloric Acid → 5'-Methyl-3,4,5,6-tetrahydro[2,3']bipyridinyl dihydrochloride

HRID 643771Notes

Reaction equation

HRID 643771 reaction equation
C(N(C[N:7]1[CH2:12][CH2:11][CH2:10][C:9](=[C:13](O)[C:14]2[CH:15]=[N:16][CH:17]=[C:18]([CH3:20])[CH:19]=2)C1=O)CC)C.[ClH:23]>CC(C)=O.C(O)(C)C>[ClH:23].[ClH:23].[CH3:20][C:18]1[CH:19]=[C:14]([C:13]2[CH2:9][CH2:10][CH2:11][CH2:12][N:7]=2)[CH:15]=[N:16][CH:17]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 670247281-Diethylaminomethyl-3-[hydroxy-(5-methylpyridin-3-yl)methylene]piperidin-2-one

Product 1

HCID 670246865'-Methyl-3,4,5,6-tetrahydro[2,3']bipyridinyl dihydrochlorideYield 85%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of diisopropylamine (4.4 mL, 31.4 mmol) in tetrahydrofuran (20 mL) at −78° C. was added a 2.5 M solution of n-butyllithium in hexanes (12 mL, 30 mmol). The solution was allowed to warm to rt over 30 min and was re-cooled to −78° C. A solution of 1-diethylaminomethyl-piperidin-2-one (3.87 g, 21.0 mmol) in tetrahydrofuran (10 mL) was added to the lithium diisopropylamide via syringe. The reaction mixture was maintained at −78° C. for 1 h and was treated with a solution of 5-methylnicotinic acid methyl ester (2.12 g, 14.0 mmol) in tetrahydrofuran (20 mL) via syringe. The reaction mixture was allowed to warm to rt and was maintained overnight. The reaction mixture was quenched with water (30 mL) and was extracted with ether (2 x). The combined organic layers were dried over magnesium sulfate and concentrated in vacuo. The residue was purified by chromatography [1/0 to 1/1 ethyl acetate/(70/30/1 ethyl acetate/methanol/ammonium hydroxide)] to provide 560 mg (13%) of 1-diethylaminomethyl-3-[hydroxy-(5-methylpyridin-3-yl)methylene]piperidin-2-one. To a solution of the piperidin-2-one (550 mg, 1.8 mmol) in acetone (101 mL) was added conc. hydrochloric acid (2 L) and the reaction mixture was heated at 100° C. overnight. The reaction mixture was allowed to cool to rt, diluted with isopropyl alcohol, and allowed to stand at 0° C. The product was isolated by filtration, thus providing 400 mg (85%) of 5′-methyl-3,4,5,6-tetrahydro[2,3′]bipyridinyl dihydrochloride.

Workup

  1. temperatureto cool to rt
  2. customto stand at 0° C
  3. customThe product was isolated by filtration

Sources & evidence

ORD record
ord-1bd02802d4f14a2a9ce4572108ddb5e2
Source dataset
uspto-grants-2010_04
Patent number
US07700630B2

Reaction notes

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