Lithium hydroxide, monohydrate → 4-(5-(2,2,2-Trifluoroacetyl)thiophen-2-yl)butanoic acid

HRID 874990Notes

Reaction equation

[F:1][C:2]([F:18])([F:17])[C:3]([C:5]1[S:9][C:8]([CH2:10][CH2:11][CH2:12][C:13]([O:15]C)=[O:14])=[CH:7][CH:6]=1)=[O:4].O[Li].O>C1COCC1.O>[F:18][C:2]([F:1])([F:17])[C:3]([C:5]1[S:9][C:8]([CH2:10][CH2:11][CH2:12][C:13]([OH:15])=[O:14])=[CH:7][CH:6]=1)=[O:4]

Participants

Conditions

Temperature: 0 °C

Procedure

Methyl 4-(5-(2,2,2-trifluoroacetyl)thiophen-2-yl)butanoate (250 mg, 0.89 mmol) was dissolved in THF-H2O (15 MI, 2:1 v/v) and cooled to 0° C. LiOH.H2O (35 mg, 0.89 mmol) was added and the reaction mixture was allowed to warm up to room temperature and stirred for 1.5 h. Solvent was removed under reduced pressure and the aqueous layer was washed with EtOAc. The Ph of the aqueous layer was adjusted to 2-3 using 1.5N HCl. The product was extracted with EtOAc. The combined extracts were dried over anhydrous sodium sulfate and concentrated under reduced pressure to get 4-(5-(2,2,2-trifluoroacetyl)thiophen-2-yl)butanoic acid (220 mg, crude), which was carried through without further purification. 1H NMR (300 MHz, DMSO-d6) δ 12.13 (br s, 1H), 8.00-7.98 (m, 1H), 7.21-7.19 (d, J=3.9 Hz, 1H), 2.98-2.93 (t, J=7.7 Hz, 2H), 2.31-2.26 (m, 2H), 1.93-1.83 (m, 2H). MS (ESI) m/z: Calculated for C10H9F3O3S: 266.02. found: 264.8 (M−H)−

Workup

temperatureto warm up to room temperature
customSolvent was removed under reduced pressure
washthe aqueous layer was washed with EtOAc
extractionThe product was extracted with EtOAc
dry with materialThe combined extracts were dried over anhydrous sodium sulfate
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-9754a2007e45436698443dad1b50282b
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08981084B2

Reaction notes

Loading…