Hydrochloric Acid → 1,1,1-Trifluoro-3-nitro-2-pentanol

Temperature

60 °C

1-Nitropropane (3.25 g, 36.6 mmol), trifluoroacetaldehyde ethyl hemiacetal (5.85 g, 36.6 mmol, 90% purity) and powdered K2CO3 (0.34 g, 2.5 mmol) were mixed and stirred at 60° C. for 3 h and then at room temperature for 3 days. Brine (10 ml) and 1N aqueous HCl (10 ml) were added and the lower organic layer separated. The aqueous layer was extracted with ether (2×30 ml) and the combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under vacuum. The residue was purified by flash chromatography on silica gel with a gradient elution of CH2Cl2:hexane (50:50), CH2Cl2:hexane (75:25), CH2Cl2 (100%) and MeOH:CH2Cl2 (5:95) to give the product as a waxy white solid (4.4 g, 64%). δH (CDCl3, 500 MHz) 1.04-1.00 (3 H, m, CHCH2CH3), 2.16-1.99 (2 H, m, CHCH2CH3), 4.37 (1 H, s, b, OH), 4.71-4.59 (2 H, m, 2×CH); δC (CDCl3, 500 MHz) dq (126.79, 126.70; 124.55, 124.46; 122.30, 122.21; 120.06, 119.96, CF3), two peaks (88.34, 87.60 CH NO2), eight peaks (71.13, 70.87, 70.81, 70.62, 70.56, 70.36, 70.30, 70.05 CHOH), two peaks (23.57 and 21.98 CH2), two peaks (9.77 and 9.66 CH3); 71.5 (CH), 54.03 (CH), 25.5 (CH2), 11.05 (CH3). 19F NMR δ −76.2 and −77.5

1. waitat room temperature for 3 days
2. customthe lower organic layer separated
3. extractionThe aqueous layer was extracted with ether (2×30 ml)
4. washthe combined organic layers were washed with brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under vacuum
8. customThe residue was purified by flash chromatography on silica gel with a gradient elution of CH2Cl2:hexane (50:50), CH2Cl2:hexane (75:25), CH2Cl2 (100%) and MeOH:CH2Cl2 (5:95)

ORD record

ord-cbeb53d610da447eb534c030bc5bce80

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592581B2