Trimethylsilyl isocyanate → 4-(2-Tert-butoxycarbonylaminoethyl)piperidine-1-carboxamide

HRID 2039563

Reaction equation

[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Si]([N:21]=[C:22]=[O:23])(C)C>ClCCl>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH:11]1[CH2:12][CH2:13][N:14]([C:22]([NH2:21])=[O:23])[CH2:15][CH2:16]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 25 °C

Procedure

4-(2-tert-Butoxycarbonylaminoethyl)piperidine (500 mg, 2.19 mmoles) was dissolved in anhydrous dichloromethane (10 mL) and trimethylsilylisocyanate (2.96 mL, 21.9 mmoles) was added. The mixture was stirred under argon at 25° C. for 3.25 h. The mixture was diluted with dichloromethane and washed with saturated aqueous sodium bicarbonate. The organic layer was dried (MgSO4), filtered, evaporated to dryness and chromatographed on a silica gel column (15×5 cm) using 5% (10% conc. ammonium hydroxide in methanol)-dichloromethane as the eluant to give 4-(2-tert-butoxycarbonylaminoethyl)piperidine-1-carboxamide (308.2 mg, 52%): FABMS: m/z 272.0 (MH+); HRFABMS: m/z 272.1965 (MH+). Calcd. for C13H26O3N3: m/z 272.1974; δH (CDCl3) 1.20 (2H, m, CH2), 1.47 (9H, s, —COOC(CH3)3), 1.45-1.55 (3H, m, CH/CH2), 1.75 (2H, m, CH2), 2.82 (2H, m, CH2), 3.19 (2H, m, CH2), 3.96 (2H, m, CH2), 4.64 (2H, m, CH2) and 4.70 ppm (1H, bm, NH); δC (CDCl3) CH3: 28.5, 28.5, 28.5; CH2: 31.8, 31.8, 36.7, 38.0, 44.5, 44.5; CH: 33.4; C: 79.2, 156.7, 158.1.

Workup

washwashed with saturated aqueous sodium bicarbonate
dry with materialThe organic layer was dried (MgSO4)
filtrationfiltered
customevaporated to dryness
customchromatographed on a silica gel column (15×5 cm)

Sources & evidence

ORD record: ord-d4c6e0bf97004de4be4d2d9025dda210
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08580782B2

Linked notes

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