Trimethylsilyl isocyanate → 3-(Tert-butoxycarbonylaminomethyl)piperidine-1-carboxamide

HRID 459717Notes

Reaction equation

[C:1]([O:5][C:6]([NH:8][CH2:9][CH:10]1[CH2:15][CH2:14][CH2:13][NH:12][CH2:11]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Si]([N:20]=[C:21]=[O:22])(C)C>ClCCl>[C:1]([O:5][C:6]([NH:8][CH2:9][CH:10]1[CH2:15][CH2:14][CH2:13][N:12]([C:21]([NH2:20])=[O:22])[CH2:11]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 25 °C

Procedure

3(R/S)-(tert-Butoxycarbonylaminomethyl)piperidine (3 g, 14.0 mmoles) was dissolved in anhydrous dichloromethane (50 mL) and trimethylsilylisocyanate (9.68 g, 11.4 mL, 84.0 mmoles) was added. The mixture was stirred under argon at 25° C. for 68 h. Additional trimethylsilylisocyanate (4.84 g, 5.7 mL, 42.0 mmoles) was added and the mixture was stirred at 25° C. for a total of 90 h. The mixture was evaporated to dryness and chromatographed on a silica gel column (30×5 cm) using 2% (10% conc. ammonium hydroxide in methanol)-dichloromethane as the eluant to give 3-(tert-butoxycarbonylaminomethyl)piperidine-1-carboxamide (3.05 g, 85%): FABMS: m/z 258.1 (MH+); HRFABMS: m/z 258.1816 (MH+). Calcd. for C12H24O3N3: m/z 258.1818; δH (CDCl3) 1.22 91H, m, CH2), 1.42 (9H, s, —COOC(CH3)3), 1.48 (1H, m, CH2), 1.67 (2H, m, CH2), 1.78 (1H, m, CH), 2.80 (1H, m, CH2), 2.99, 3H, m, CH2), 3.59 (1H, m, CH2O 3.69 (1H, m, CH2), 4.76 (2H, bm, CONH2) and 4.98 ppm (1H, bm, NH); δC (CDCl3) CH3: 28.5, 28.5, 28.5; CH2: 24.0, 28.3, 43.2, 45.1, 47.8; CH: 36.5; C: 79.4, 156.3, 158.5.

Workup

stirringthe mixture was stirred at 25° C. for a total of 90 h
customThe mixture was evaporated to dryness
customchromatographed on a silica gel column (30×5 cm)

Sources & evidence

ORD record: ord-9c0ce70a3f3948ee9064401a703cdc84
Source dataset: uspto-grants-2007_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07196078B2

Reaction notes

Loading…