Triethylamine → [6-Chloro-4-(3,3-dimethyl-but-1-ynyl)-pyridin-3-yl]-carbamic acid tert-butyl ester

HRID 513069

Reaction equation

[C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:9]=[N:10][C:11]([Cl:15])=[CH:12][C:13]=1I)([CH3:4])([CH3:3])[CH3:2].[CH3:17][C:18]([CH3:22])([CH3:21])[C:19]#[CH:20].C(N(CC)CC)C>C1(C)C=CC=CC=1.O.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:9]=[N:10][C:11]([Cl:15])=[CH:12][C:13]=1[C:20]#[C:19][C:18]([CH3:22])([CH3:21])[CH3:17])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 70 °C

Procedure

To a deoxygenated solution of (6-chloro-4-iodo-pyridin-3-yl)-carbamic acid tert-butyl ester (23.3 g, 65.6 mmol), 3,3-dimethyl-but-1-yne (53.8 g, 0.656 mol), CuI (623 mg, 3.3 mmol) and triethylamine (13.3 g, 0.13 mol) in toluene (150 mL) and water (50 mL) was added Pd(PPh3)2Cl2 (2.30 g, 3.28 mmol) under N2. The mixture was heated at 70° C. and stirred for 24 hours. The solid was filtered off and washed with ethyl acetate (200 mL×3). The filtrate was evaporated under reduced pressure to obtain a residue, which was purified by column (petroleum ether/ethyl acetate=10/1) to give [6-chloro-4-(3,3-dimethyl-but-1-ynyl)-pyridin-3-yl]-carbamic acid tert-butyl ester (15.8 g, 78%). 1H NMR (300 MHz, CDCl3) δ 9.10 (br s, 1H), 7.21 (s, 1H), 6.98 (br s, 1H), 1.53 (s, 9H), 1.36 (s, 9H).

Workup

filtrationThe solid was filtered off
washwashed with ethyl acetate (200 mL×3)
customThe filtrate was evaporated under reduced pressure
customto obtain a residue, which
customwas purified by column (petroleum ether/ethyl acetate=10/1)

Sources & evidence

ORD record: ord-625d21f062fd45b0ae63ef512db8e683
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09102672B2

Linked notes

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