Sulfuric Acid → 3-(Aminomethyl)piperidine-1-carboxamide

HRID 2042017Notes

Reaction equation

C(OC([NH:8][CH2:9][CH:10]1[CH2:15][CH2:14][CH2:13][N:12]([C:16]([NH2:18])=[O:17])[CH2:11]1)=O)(C)(C)C.S(=O)(=O)(O)O>CO.O1CCOCC1>[NH2:8][CH2:9][CH:10]1[CH2:15][CH2:14][CH2:13][N:12]([C:16]([NH2:18])=[O:17])[CH2:11]1

Participants

Conditions

Temperature: 25 °C

Procedure

3-(tert-Butoxycarbonylaminomethyl)piperidine-1-carboxamide (150 mg, 0.583 mmoles) (prepared as described in Preparative Example 241, Step A above) was dissolved in methanol (3 mL). 10% conc. sulfuric acid in 1,4-dioxane (7.9 mL) was added and the mixture was stirred at 25° C. for 1 h. The mixture was diluted with methanol and BioRad AG1-X8 resin (OH− form) was added until the pH was basic. The resin was filtered off, washed with methanol, evaporated to dryness and chromatographed on a silica gel column (15×2 cm) using dichloromethane followed by 15% (10% conc, ammonium hydroxide in methanol)-dichloromethane as the eluant to give the 3-(aminomethyl)piperidine-1-carboxamide (80 mg, 87%): FABMS: m/z 158.1 (MH+); HRFABMS: m/z 158.1294 (MH+). Calcd. for C7H16N3O: m/z 158.1293; δH (CDCl3+drop CD3OD) 1.20 (1H, m, CH2), 1.48 (1H, m, CH2), 1.60 (1H, m, CH), 1.68 (1H, m, CH2), 1.83 (1H, m, CH2), 2.64 (bm, 2H, —CH2NH2), 2.82 (1H, m, CH2), 3.02 (1H, m, CH2), 2.98 (2H, m, CH2), 3.70 (1H, m, —CH2NH2), 3.78 (1H, m, —CH2NH2) and 5.24 ppm (1H, bs, NH); δC (CDCl3+drop CD3OD) CH2: 24.1, 28.6, 44.0, 44.8, 47.9; CH: 38.3; C, 159.0.

Workup

additionresin (OH− form) was added until the pH
filtrationThe resin was filtered off
washwashed with methanol
customevaporated to dryness
customchromatographed on a silica gel column (15×2 cm)

Sources & evidence

ORD record: ord-dedbffd8edbe40cbacb91f2b6d183928
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08586576B2

Reaction notes

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