Trifluoroacetic acid → 2-[1-(4-fluorophenyl)-1H-pyrrol-3-yl]-acetic acid methyl ester

According to the procedure described in Example 1(c) for the preparation of N-(8-oxo-4-oxa-1,7-diaza-tricyclo[9.6.1.012,17]octadeca-11(18),12,14,16-tetraen-9-yl)-3(3-phenyl-1H-pyrrol-1-yl)succinamic acid benzyl ester, to a mixture of crude methyl 2-(2,5-dimethoxy-tetrahydrofuran-3-yl)-acetate (120 mg, ˜0.58 mmol) and 4-fluoroaniline (50 μL, 0.53 mmol) in 1,2-dichloroethane (10 mL) was added trifluoroacetic acid (0.2 mL, 0.26 mmol). After 16 hours at 80° C., the resultant mixture was partitioned between EtOAc and 1M pH 7 phosphate buffer. The separated aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated to a crude oil, which was purified via flash column chromatography with 0-15% EtOAc/hex gradient eluant to yield 100 mg (77%) of 2-[1-(4-fluorophenyl)-1H-pyrrol-3-yl]-acetic acid methyl ester as an oil. 1H NMR: δ 7.34-7.30 (m, 2H), 7.10 (t, 2H, J=8.6 Hz), 6.96-6.94 (m, 2H), 6.28 (t, 1H, J=2.2 Hz), 3.72 (s, 3H), 3.56 (s, 2H). Anal. Calculated for C13H12NO2F•0.6 H2O: C, 63.98; H, 5.45; N, 5.74. Found: C, 64.01; H, 5.04; N, 5.65.

1. customthe resultant mixture was partitioned between EtOAc and 1M pH 7 phosphate buffer
2. extractionThe separated aqueous layer was extracted with EtOAc
3. washThe combined organic layers were washed with brine
4. dry with materialdried over Na2SO4
5. concentrationconcentrated to a crude oil, which
6. customwas purified via flash column chromatography with 0-15% EtOAc/hex gradient eluant

ORD record

ord-65798a8d5ff046e3b0b5c1ef317728f7

Source dataset

uspto-grants-2001_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06174915B1