氢氧化钠 → 1-苄基-3-三氟甲基-哌嗪

A solution of 3,3,3-trifluoro-2-oxopropanal (0.31 g, 2.3 mmol; Intermediate 43) in DMF (10 mL) was cooled to 0° C. and a solution of N-benzylethane-1,2-diamine (0.37 g, 2.72 mmol) in DMF (10 mL) was added. After being stirred at room temperature overnight, the mixture was concentrated in vacuo. The residue was redissolved in THF (5 mL) and citrate buffer (5.3 mL; 0.4 M), followed by NaBH3CN (0.31 g, 4.9 mmol), were added. The resulting mixture was stirred at room temperature overnight. The mixture was made basic (pH 8) with aqueous NaOH (8 mL; 1 M) and the aqueous layer was extracted twice with DCM (15 mL). The combined organic layers were dried (Na2SO4) and concentrated. The residue was purified by LC-MS prep to give 1-benzyl-3-(trifluoromethyl)piperazine (66 mg, 12%). HPLC 94%, RT=1.25 min (System A; 10-97% MeCN over 3 min). 1H NMR (270 MHz, CDCl3) δ ppm 2.77 (s, 2H) 3.17-3.31 (m, 1H) 3.32-3.64 (m, 3H) 3.83-4.02 (m, 1H) 4.13-4.31 (m, 2H) 6.68 (s, 1H) 7.30-7.55 (m, 5H). MS (ESI+) m/z 245. *Previously described in Rec. Trav. Chim. Pays-Bas 1995, 114, 97-102.

1. concentrationthe mixture was concentrated in vacuo
2. dissolutionThe residue was redissolved in THF (5 mL)
3. additionwere added
4. stirringThe resulting mixture was stirred at room temperature overnight
5. extractionthe aqueous layer was extracted twice with DCM (15 mL)
6. dry with materialThe combined organic layers were dried (Na2SO4)
7. concentrationconcentrated
8. customThe residue was purified by LC-MS prep

ORD记录

ord-c5ee0fe8b8d74356bf0a22c54b5ce2e7

来源数据集

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

专利号

US07820675B2