Trifluoroacetic acid → Trifluoroacetic acid

HRID 1424519Notes

Reaction equation

[C:1]([OH:7])([C:3]([F:6])([F:5])[F:4])=[O:2].[S:8]([O-:35])([O:11][N:12]1[C:18](=[O:19])[N:17]2[CH2:20][C@H:13]1[CH2:14][CH2:15][C@H:16]2[C:21]1[CH:25]=[C:24]([CH2:26][NH:27]C(OC(C)(C)C)=O)[O:23][N:22]=1)(=[O:10])=[O:9].[Na+]>C(Cl)Cl.C(OCC)C>[S:8]([OH:35])([O:11][N:12]1[C:18](=[O:19])[N:17]2[CH2:20][C@H:13]1[CH2:14][CH2:15][C@H:16]2[C:21]1[CH:25]=[C:24]([CH2:26][NH2:27])[O:23][N:22]=1)(=[O:10])=[O:9].[C:1]([OH:7])([C:3]([F:6])([F:5])[F:4])=[O:2]

Participants

Conditions

Temperature: 0 °C

Procedure

TFA (0.40 mL) was added to a 0° C. solution of sodium (2S,5R)-2-(5-(tert-butoxycarbonylaminomethyl)isoxazol-3-yl)-7-oxo-1,6-diaza-bicyclo[3.2.1]octan-6-yl sulfate (54 mg, 0.12 mmol) in dry DCM (1.2 mL). The reaction mixture was stirred at 0° C. for 30 minutes to 1 h and then diluted with diethyl ether. The precipitate was collected via centrifugation, washed with ether (3×) and further dried under high vacuum to provide (2S,5R)-2-(5-(aminomethyl)isoxazol-3-yl)-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl hydrogen sulfate as a TFA salt (˜30 mg). ESI-MS (EI+, m/z): 319.2. The TFA salt (˜30 mg) was further purified by prep-HPLC using ammonium formate buffer to provide (2S,5R)-2-(5-(aminomethyl)isoxazol-3-yl)-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl hydrogen sulfate (601, 10 mg, 26%) as a white solid. ESI-MS (EI+, m/z): 319.21. 1H NMR (300 MHz, D2O) δ 6.61 (s, 1H), 4.68-4.65 (m, 1H), 4.35 (s, 2H), 4.17-4.14 (m, 1H), 3.14-3.10 (m, 1H), 2.95-2.91 (m, 1H), 2.31-1.80 (m, 4H).

Workup

customThe precipitate was collected via centrifugation
washwashed with ether (3×)
customfurther dried under high vacuum

Sources & evidence

ORD record: ord-cf8eb89ae17f418790b16bcfb968279c
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08927724B2

Reaction notes

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