Triethylamine → tert-butyl 4-((3-iodo-1-isopropyl-1H-pyrazol-4-yl)methyl)-4-isocyanatopiperidine-1-carboxylate

HRID 880902Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH2:17][C:18]2[C:19]([I:26])=[N:20][N:21]([CH:23]([CH3:25])[CH3:24])[CH:22]=2)(C(O)=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N:29]([CH2:32]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:41])C=CC=CC=1>C1(C)C=CC=CC=1>[I:26][C:19]1[C:18]([CH2:17][C:11]2([N:29]=[C:32]=[O:41])[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]2)=[CH:22][N:21]([CH:23]([CH3:24])[CH3:25])[N:20]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of 1-(tert-butoxycarbonyl)-4-((3-iodo-1-isopropyl-1H-pyrazol-4-yl)methyl)piperidine-4-carboxylic acid (430 mg, 0.90 mmol) in toluene (10 mL) was added triethylamine (0.15 mL, 1.08 mmol) and diphenylphosphoryl azide (0.24 mL, 1.08 mmol). The mixture was heated at 120° C. for 3 hours, the volatiles were removed under reduced pressure and the resultant oil was purified by flash chromatography (7-60% ethyl acetate/heptanes, 25 g silica gel) to yield tert-butyl 4-((3-iodo-1-isopropyl-1H-pyrazol-4-yl)methyl)-4-isocyanatopiperidine-1-carboxylate (280 mg) as a clear oil. FT-IR (cm−1): 2253; 1H NMR (400 MHz, CDCl3, δ): 7.27 (s, 1H), 4.50 (m, 1H), 4.03 (br. s., 2H), 2.97 (br. s., 2H), 2.65 (s, 2H), 1.65 (m, 4H), 1.50 (s, 6H), 1.47 (s, 9H).

Workup

customthe volatiles were removed under reduced pressure
customthe resultant oil was purified by flash chromatography (7-60% ethyl acetate/heptanes, 25 g silica gel)

Sources & evidence

ORD record: ord-e984e93cc5594d3797b49232b9b1824f
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08993586B2

Reaction notes

Loading…