Trichloroacetonitrile → [2-Phenyl-1-(thiophene-2-sulfonylamino)-ethyl]-phosphonic acid mono-(2-chloropyridin-3-yl) ester ammonium salt

HRID 896989Notes

Reaction equation

[C:1]1([CH2:7][CH:8]([P:18](=[O:21])([OH:20])[OH:19])[NH:9][S:10]([C:13]2[S:14][CH:15]=[CH:16][CH:17]=2)(=[O:12])=[O:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:22][C:23]1[C:28](O)=[CH:27][CH:26]=[CH:25][N:24]=1.ClC(Cl)(Cl)C#N>N1C=CC=CC=1>[NH4+:9].[Cl:22][C:23]1[C:28]([O:21][P:18]([CH:8]([NH:9][S:10]([C:13]2[S:14][CH:15]=[CH:16][CH:17]=2)(=[O:11])=[O:12])[CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)(=[O:19])[O-:20])=[CH:27][CH:26]=[CH:25][N:24]=1

Participants

Conditions

Temperature: 105 °C

Procedure

To a sealed tube containing phosphonic acid (xiii) (134 mg; 0.39 mmol) and 2-chloro-3-pyridinol (60 mg; 0.46 mmol) was added pyridine (1.9 mL) and trichloroacetonitrile (270 μL; 2.7 mmol). The reaction was heated to 105° C. for 6 hours then was cooled and concentrated. The residue was purified by flash chromatography (chloroform-methanol-concentrated ammonium hydroxide; 9:2:0.1) to yield the ammonium salt 46 (100 mg, 54%) as a colorless solid: 1H NMR: (400 MHz, CD3OD) δH 2.87 (td, J=9, 14 Hz,. 1H, CHPh), 3.28-3.36 (m, 1H, CHPh), 4.01 (ddd, J=4.5, 9, 17 Hz, 1H, NCHP), 6.81 (dd, J=3.5, 5 Hz, 1H, Ar—H), 7.07-7.21 (m, 6H. Ar—H), 7.28 (dd, J=4.5, 8 Hz, 1H, Ar—H), 7.46 (dd, J=1.5, 5 Hz, 1H, Ar—H), 7.91-7.93 (m, 1H, Ar—H), 7.99-8.02 (m, 1H, Ar—H); 31P NMR: (162 MHz, CD3OD) δP 17.0; 13C NMR: (100 MHz, DMSO-D6) δC 38.3, 55.6, (d, J=147.6 Hz), 124.3, 126.7, 128.1, 130.1, 130.4, 131.8, 132.1, 140.3 (d, J=10 Hz), 142.4, 142.7, 144.5, 147.9.

Workup

temperaturethen was cooled
concentrationconcentrated
customThe residue was purified by flash chromatography (chloroform-methanol-concentrated ammonium hydroxide; 9:2:0.1)

Sources & evidence

ORD record: ord-bf70ee65b4104336948e614d982ffc62
Source dataset: uspto-grants-2005_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06921756B2

Reaction notes

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