Water → HCID 66602080, compound

HRID 604309Notes

Reaction equation

HRID 604309 reaction equation
[NH2:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1.[CH3:16][S:17](Cl)(=[O:19])=[O:18].C(N(CC)CC)C.O>C(Cl)Cl>[C:12]([O:11][C:9]([N:6]1[CH2:7][CH2:8][CH:3]([CH:2]([S:17]([CH3:16])(=[O:19])=[O:18])[NH2:1])[CH2:4][CH2:5]1)=[O:10])([CH3:15])([CH3:14])[CH3:13]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 7368171-Boc-4-(aminomethyl)piperidine

Product 1

HCID 66602080HCID 66602080, compoundYield 102.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of t-butyl 4-(aminomethyl)tetrahydropyridine-1(2H)-carboxylate (1.50 g, 7.0 mmol, 1 eq) in DCM (anhydrous) (20 mL) is added methanesulfonyl chloride (569 μL, 7.35 mmol, 1.05 eq). To this add triethylamine (2.05 ml, 14.7 mmol, 2.1 eq), dropwise over 15 min. Stir at room temperature for 3 hr. and then add water (20 mL) with stirring. The organic phase is isolated then washed with 2 M aqueous hydrochloric acid (20 mL), and saturated aqueous sodium hydrogen carbonate solution (20 mL). Dry the organic layer (magnesium sulphate) and concentrate to give 4-(methanesulfonyl-aminomethyl)-piperidine-1-carboxylic acid t-butyl ester (2.1 g, 102%). MS (ES): m/z=315.1 [M+Na]+. To a solution of this compound (2.1 g, 7.2 mmol, 1 eq) in 1,4-dioxane (25 mL) add 4 M hydrogen chloride in dioxane (17.95 mL, 72 mmol, 10 eq). Stir at room temperature for 29 hr., basify with 2 M aqueous sodium hydroxide, and then add DCM (20 mL). Separate the layers and extract the aqueous twice with DCM (20 mL), dry the combined organics over magnesium sulphate, filter and concentrate. Extract the aqueous layer a further four times with 3:1 chloroform:isopropanol (25 mL). Concentrate the aqueous layer to less than 10 mL volume and extract again with four times with 3:1 chloroform:isopropanol (25 mL). Combine with all the previous organic extracts to give N-piperidin-4-ylmethyl-methanesulfonamide (703 mg, 50%). MS (m/z): 193 (M+1).

Workup

  1. customThe organic phase is isolated
  2. washthen washed with 2 M aqueous hydrochloric acid (20 mL), and saturated aqueous sodium hydrogen carbonate solution (20 mL)
  3. dry with materialDry the organic layer (magnesium sulphate)
  4. concentrationconcentrate

Sources & evidence

ORD record
ord-f90d2135c3694fb584209ab8ef3e056d
Source dataset
uspto-grants-2011_03
Patent number
US07910588B2

Reaction notes

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