1,1,1,3,3,3-Hexafluoro-2-propanol → HCID 89677180, compound

A 50 mL round-bottom flask was charged with 1,1,1,3,3,3-hexafluoropropan-2-ol (168 mg, 1.00 mmol, 1.00 equiv), triphosgene (99.0 mg, 0.330 mmol, 0.33 equiv), and acetonitrile (10 mL). N,N-diisopropylethylamine (471 mg, 3.64 mmol, 3.65 equiv) was added dropwise. The mixture was stirred at room temperature for 2 hours. 2-Methyl-1-[(4-phenylphenyl)methyl]piperazine (266 mg, 1.00 mmol, 1.00 equiv) was added. The resulting solution was stirred for 2 hours at room temperature and diluted with water (20 mL). The resulting solution was extracted with dichloromethane (3×20 mL) and the organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on a silica gel column with ethyl acetate/petroleum ether (1/3). The product (208 mg) was purified by preparative HPLC using the following gradient conditions: 20% CH3CN/80% Phase A increasing to 80% CH3CN over 10 min, then to 100% CH3CN over 0.1 min, holding at 100% CH3CN for 1.9 min, then reducing to 20% CH3CN over 0.1 min, and holding at 20% for 1.9 min, on a Waters 2767-5 Chromatograph. Column: Xbridge Prep C18, 19*150 mm 5 um; Mobile phase: Phase A: aqueous NH4HCO3 (0.05%); Phase B: CH3CN; Detector, UV220 & 254 nm. Purification resulted in 91.3 mg (20% yield) of 1,1,1,3,3,3-hexafluoropropan-2-yl 3-methyl-4-[(4-phenylphenyl)methyl]piperazine-1-carboxylate as colorless oil. 1H NMR 400 MHz (CDCl3) δ 7.54-7.62 (m, 4H), 7.33-7.49 (m, 5H), 5.75-5.80 (m, 1H), 3.98-4.23 (m, 1H), 3.75-3.86 (m, 2H), 3.01-3.48 (m, 3H), 2.62-2.77 (m, 2H), 2.20-2.27 (m, 1H), 1.19 (br, 3H). LCMS (ESI, m/z): 461 [M+H]+.

1. stirringThe resulting solution was stirred for 2 hours at room temperature
2. extractionThe resulting solution was extracted with dichloromethane (3×20 mL)
3. dry with materialthe organic layers were dried over anhydrous sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customThe residue was chromatographed on a silica gel column with ethyl acetate/petroleum ether (1/3)
7. customThe product (208 mg) was purified by preparative HPLC
8. wait20% CH3CN/80% Phase A increasing to 80% CH3CN over 10 min
9. waitto 100% CH3CN over 0.1 min
10. waitholding at 100% CH3CN for 1.9 min
11. waitreducing to 20% CH3CN over 0.1 min
12. waitholding at 20% for 1.9 min, on a Waters 2767-5 Chromatograph
13. customPurification

ORD record

ord-b799727c148e4ea69ce2f387f664e30d

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09133148B2