Diisopropylethylamine → N-(2-tert-butoxycarbonylamino-5-trifluoromethyl-phenyl)-malonamic acid benzyl ester

The compound (2-amino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (1.8 g, 6.6 mmol, see procedure 4a) was dissolved in 32 mL of 2:1 CH2Cl2/DMF. The resultant solution was charged sequentially with mono-benzyl malonate (1.28 g, 6.6 mmol), N,N-diisopropylethylamine (5.8 mL, 33 mmol) and HATU (3.0 g, 7.9 mmol). The mixture was stirred for 12 h at RT, concentrated in vacuo, and partitioned between EtOAc and sat. NH4Cl. The aqueous phase was extracted with EtOAc (1×). The combined organic extracts were washed with sat. NaHCO3 and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography to provide N-(2-tert-butoxycarbonylamino-5-trifluoromethyl-phenyl)-malonamic acid benzyl ester (2.3 g, 77% yield). A portion (860 mg) of this material was dissolved in 10 mL of THF. The resultant solution was charged with 30 mL of acetic acid, heated at 65° C. for 3 h, and concentrated in vacuo. The residue was purified by flash chromatography to provide (5-trifluoromethyl-1H-benzoimidazol-2-yl)-acetic acid benzyl ester (343 mg, 54% yield). MS found: (M+H)+=335.2.

1. concentrationconcentrated in vacuo
2. custompartitioned between EtOAc and sat. NH4Cl
3. extractionThe aqueous phase was extracted with EtOAc (1×)
4. washThe combined organic extracts were washed with sat. NaHCO3 and brine
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by flash chromatography

ORDレコード

ord-1274b2c2dcbf472c9689add6a18046d0

出典データセット

uspto-grants-2007_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07230133B2