Triethylamine → Methyl 2-{[4-(4-bromophenyl)-1,3-thiazol-2-yl]amino}-4,4,4-trifluorobutanoate

HRID 1436396Notes

Reaction equation

Cl.[CH3:2][O:3][C:4](=[O:12])[CH:5]([NH2:11])[CH2:6][C:7]([F:10])([F:9])[F:8].C(N(CC)CC)C.[Br:20][C:21]1[CH:26]=[CH:25][C:24]([C:27](=O)[CH2:28][S:29][C:30]#[N:31])=[CH:23][CH:22]=1>C(O)C>[Br:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[N:31]=[C:30]([NH:11][CH:5]([CH2:6][C:7]([F:9])([F:8])[F:10])[C:4]([O:3][CH3:2])=[O:12])[S:29][CH:28]=2)=[CH:23][CH:22]=1

Participants

Conditions

Temperature: 55 °C

Procedure

2-Amino-4,4,4-trifluoro-butyric acid methyl ester hydrochloride (1.1 g, 5.3 mmol) was dissolved in 30 mL of ethanol and 2-(4-bromophenyl)-2-oxoethyl thiocyanate, prepared in step 1 of Example 1, (1.23 g, 4.8 mmol) was added followed by triethylamine (0.73 mL, 5.3 mmol). The mixture was heated to 55° C. for 18 h then cooled and concentrated under reduced pressure. Flash chromatography (5% acetone/hexane) afforded methyl 2-{[4-(4-bromophenyl)-1,3-thiazol-2-yl]amino}-4,4,4-trifluorobutanoate (1.21 g, 56%) as a white solid. mp 113-114° C. HRMS: calcd for C14H12BrF3N2O2S+H+, 408.98277; found (ESI, [M+H]+), 408.9831. Analytical HPLC: retention time 11.5 min, 210-370 nm the Xterra® RP18 column, 3.5μ, 150×4.6 mm 40° C. 85/15-5/95 (Ammon. Form. Buff. pH=3.5/ACN+MeOH) for 10 min, hold 4 min, 1.2 mL/min 5 μL injection.

Workup

additionwas added
temperaturethen cooled
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-3b9d86f04ad847acad811bdce9a31de8
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07618990B2

Reaction notes

Loading…