Diisopropylamine → Dimethyl-[3-(4-nitro-2-trifluoromethyl-phenyl)-prop-2-ynyl]-amine

t-Bu3P (0.25 M in dioxane, 8.9 mL, 2.2 mmol, 0.2 equiv), 3-dimethylamino-1-propyne (FLUKA) (1.65 mL, 15.6 mmol, 1.4 equiv), and i-Pr2NH (2.0 mL, 14.4 mmol, 1.3 equiv) are added sequentially to a mixture of 5-nitro-2-bromobenzotrifluoride (ALDRICH) (3 g, 11.1 mmol), CuI (0.148 g, 0.78 mmol, 0.07 equiv), and Pd(PhCN)2Cl2 (0.427 g, 1.1 mmol, 0.1 equiv) in dioxane (10 mL). The reaction mixture is stirred for 48 h at rt. Then, Pd(PhCN)2Cl2 (0.100 g) is added. After stirring for additional 24 h, the reaction mixture is diluted with EtOAc and H2O and filtered through a pad of Celite. The filtrate is extracted with EtOAc. The organic phase is washed with brine, dried (Na2SO4), filtered and concentrated. Purification of the crude material by silica gel column chromatography (CH2Cl2/NH3 (2 N in MeOH), 95:5) affords the title compound as a brown oil: ES-MS: 273.0 [M+H]+; single peak at tR=3.06 min (System 1); Rf=0.13 (CH2Cl2/NH3 (2 N in MeOH), 95:5).

1. stirringAfter stirring for additional 24 h
2. filtrationfiltered through a pad of Celite
3. extractionThe filtrate is extracted with EtOAc
4. washThe organic phase is washed with brine
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customPurification of the crude material by silica gel column chromatography (CH2Cl2/NH3 (2 N in MeOH), 95:5)

ORD record

ord-48463f684ac441b68d3df8c38e2b99c5

Source dataset

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08030311B2