Toluene → HCID 178444602, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 542 mg (0.71 mmol) of (2′S,3R,4′R,5′S)-6-chloro-4′-(3-chloro-2-fluorophenyl)-1′-((1S,2R)-2-hydroxy-1,2-diphenylethyl)-N-((trans)-4-hydroxycyclohexyl)-2′-neopentyl-2-oxospiro[indoline-3,3′-pyrrolidine]-5′-carboxamide in 10 mL of ethanol was cooled to 0° C. and 989 mg (1.79 mmol) of ceric ammonium nitrate was added slowly via spatula in 15 min. The reaction mixture was stirred at 0° C. for 1 hour, upon which it was treated with 4 mL of toluene, 2 mL of ethanol, 5 mL of saturated brine and 3 mL of ethyl acetate, and decanted. The organic phase was separated and the aqueous phase was extracted with 2×5 mL of ethyl acetate. The organic phases were combined and washed with 3 mL of 5% sodium carbonate. After decantation, the aqueous phase was diluted with water and reextracted with 10 mL of ethyl acetate. The organic phases were combined and successively washed with 2 mL of 11% sodium disulfite and 2 mL of saturated brine. It was then dried over magnesium sulfate and concentrated to dryness under reduced pressure. 222 mg of the residue was purified by flash chromatography on a 40 g silica cartridge (15 μm silica gel; eluting solvent: dichloromethane/acetone 75/25 v/v followed by 65/35 v/v; flow: mL/min). 0.183 g of an off-white meringue was obtained, taken up twice in diisopropyl oxide and dried at 25° C. under reduced pressure. 157 mg of (2′S,3R,4′R,5′S)-6-chloro-4′-(3-chloro-2-fluorophenyl)-N-((trans)-4-hydroxy-cyclohexyl)-2′-neopentyl-2-oxospiro[indoline-3,3′-pyrrolidine]-5′-carboxamide were obtained as a white amorphous solid. mp: 176° C. (Kofler); LC-MS: tR (min)=1.13 (91%) and 1.03 (9%); [M+H]+: m/z 562; [M−H]−: m/z 560 (method C); 1H NMR (400 MHz, DMSO-d6): 0.76 (s, 9 H); 0.85 (dd, J=1.8 and 14.3 Hz, 1H); 0.97 to 1.28 (m, 4 H); 1.38 to 1.50 (m, 2 H); 1.67 (m, 1 H); 1.80 (m, 2 H); 2.56 (t, J=12.1 Hz, 1 H); 3.23 to 3.38 (m partially hidden, 2 H); 3.45 (m, 1 H); 3.93 (d, J=9.6 Hz, 1 H); 4.22 (dd, J=9.6 and 12.1 Hz, 1 H); 4.46 (d, J=4.4 Hz, 1 H); 6.62 (d, J=8.1 Hz, 1 H); 6.70 to 6.75 (m, 2 H); 7.13 (t broad, J=7.9 Hz, 1 H); 7.31 (t broad, J=7.9 Hz, 1 H); 7.64 (t broad, J=7.9 Hz, 1 H); 7.92 (d, J=7.7 Hz, 1 H); 10.51 (s broad, 1 H).

Provenance & Evidence