4-(Difluoromethoxy)aniline

Clear colorless to orange-brown liquid

To a solution of triphosgene (65 mg, 0.5 equiv.) in EtOAc (11 mL), molecular sieves were added. To the resulting solution previously cooled to 0C, a solution of 4- (difluoromethoxy) aniline (70 mg, 1.0 equiv.) in EtOAc (11 mL) was added dropwise. The reaction mixture was stirred at 0C for 2 hours and washed with saturated aqueous solution of NaHC03 and brine. The organic layer was dried over Na2S04, filtered and evaporated in vacuo to afford the expected product (49 mg). In order to confirm the structure, 3 mg of product was dissolved in MeOH and evaporated to dryness to obtain Intermediate A. 1H NMR (300MHz, DMSO-d6) d = 9.70 (s, 1H), 7.46 (d, J = 8.7 Hz, 2H), 7.10 (d, J = 8.7 Hz, 2H), 7.09 (t, J = 74.1 Hz, 1H), 3.65 (s, 3H) ppm.General procedure: Ethyl 4-bromo-1H-indole-2-carboxylate (1 eq), Pd2(dba)3 (0.1 eq), X-phos(0.2 eq), Cs2CO3 (3 eq) and aryl amine (3 eq) was added to a microwave tube, dissolved in 1, 4-dioxane, and filled with argon gas. The microwave reaction wascarried out at 100 C for 0.5-1.5 h, and the starting material disappeared. The mixturewas cooled to room temperature and concentrated. Ethyl acetate was added todissolve the residue, and the mixture was washed with saturated brine and water, driedover anhydrous Na2SO4, and concentrated in vacuo. The crude product was purifiedby column chromatography to afford the target compound. Compounds 8m-8o, 8s, 8a-3 ~ 8a-5, 8a-13, 8a-15 ~ 8a-17, 8o-1 ~ 8o-24 were prepared with method 3.32g of NaOH was dissolved in 250mL of water, 43g of p-aminophenol was added under stirring, and the mixture was poured into a 1L autoclave after cooling to room temperature.Add 150mL of benzene and 0.5g of benzyltriethylammonium chloride (TEBA), seal the autoclave and stir to 80 C.Introduce dichlorochloromethane (Freon-22) to maintain a pressure of 0.6 MPa, stir for 8 hours, cool to room temperature, remove excess difluorochloromethane (Freon-22), and use a gas bag to recover;The benzene layer was then separated from the reaction solution, washed with saturated brine, and distilled to recover benzene, and then the remaining solution was cooled to 0 C.White crystals were precipitated and recrystallized from ethanol (-20 C) to obtain 55 g of

Molecular Weight:159.13
XLogP3:1.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:159.04957017
Monoisotopic Mass:159.04957017
Topological Polar Surface Area:35.2
Heavy Atom Count:11
Complexity:113
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes