1-Butyne → Tert-butyl 4-(but-1-ynyl)-6-chloropyridin-3-ylcarbamate

HRID 513077Notes

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].[CH:17]#[C:18][CH2:19][CH3:20].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:17]([C:13]1[CH:12]=[C:11]([Cl:15])[N:10]=[CH:9][C:8]=1[NH:7][C:6](=[O:16])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])#[C:18][CH2:19][CH3:20]

Participants

Conditions

Temperature: 70 °C

Procedure

To a deoxygenated solution of (6-chloro-4-iodo-pyridin-3-yl)-carbamic acid tert-butyl ester (6.0 g, 16.9 mmol), 1-butyne (9 g, 169 mmol), CuI (160.1 mg, 0.84 mmol) and triethylamine (3.4 g, 33.2 mmol) in toluene (40 mL) and water (14 mL) was added Pd(PPh3)2Cl2 (592 mg, 0.84 mmol) under N2 in a autoclave. The mixture was heated to 70° C. and stirred for 24 h. The solid was filtered off and washed with ethyl acetate (60 mL×3). The filtrate was evaporated under reduced pressure and the residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate, 10/1) to give tert-butyl 4-(but-1-ynyl)-6-chloropyridin-3-ylcarbamate (3.5 g, 74%). 1H-NMR (CDCl3, 300 MHz) δ 9.13 (s, 1H), 7.22 (s, 1H), 6.98 (s, 1H), 2.53 (q, J=7.5 Hz, 2H), 1.54 (s, 9H), 1.29 (t, J=7.5 Hz, 3H).

Workup

filtrationThe solid was filtered off
washwashed with ethyl acetate (60 mL×3)
customThe filtrate was evaporated under reduced pressure
customthe residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate, 10/1)

Sources & evidence

ORD record: ord-471bc8bde25f4946b3abfda180351719
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09102672B2

Reaction notes

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