Triethylamine → 3-(1-Boc-2-(r)-azetidinylmethoxy)-6-chloro-5-(trimethylsilylethynyl)pyridine

HRID 2305198Notes

Reaction equation

[C:1]([N:8]1[CH2:11][CH2:10][C@@H:9]1[CH2:12][O:13][C:14]1[CH:15]=[N:16][C:17]([Cl:21])=[C:18](Br)[CH:19]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CCN(CC)CC.[CH3:29][Si:30]([C:33]#[CH:34])([CH3:32])[CH3:31]>C1(C)C=CC=CC=1.[I+].[Cu+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([N:8]1[CH2:11][CH2:10][C@@H:9]1[CH2:12][O:13][C:14]1[CH:15]=[N:16][C:17]([Cl:21])=[C:18]([C:34]#[C:33][Si:30]([CH3:32])([CH3:31])[CH3:29])[CH:19]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 3-(1-BOC-2-(R)-azetidinylmethoxy)-6-chloro-5-bromopyridine (660 mg, 1.75 mmol) in toluene (20 mL) was added NEt3 (0.7 mL), copper (I) iodine (33 mg), tetrakis(triphenylphosphine)palladium (0) (201 mg) and (trimethylsilyl)acetylene (0.30 mL, 2.10 mmol). The reaction mixture was stirred and heated at 100° C. for 16 h. Solvent was evaporated and the residue was chromatographed (silica gel; hexane/EtoAc, 5:1 to 2:1) to afford an oil (430 mg, 62%): 1H NMR (CDCl3, 300 MHz) δ 1.42 (s, 9H), 2.20-2.40 (m, 2H), 3.80-3.92 (m, 2H), 4.10 (m, 1H), 4.30 (m,1H), 4.50 (m, 1H), 7.37 (d, 1H, J=3.0 Hz), 8.05 (d, 1H, J=3.0 Hz); MS (CI/NH3) m/z 395 (M+H)+.

Workup

customSolvent was evaporated
customthe residue was chromatographed (silica gel; hexane/EtoAc, 5:1 to 2:1)

Sources & evidence

ORD record: ord-0f8336b224414bbc84aeb43735409178
Source dataset: uspto-grants-2002_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06437138B1

Reaction notes

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