Diazomethane → HCID 57659762, compound

Participants

Reaction Conditions

Reaction Steps

An ethereal solution of diazomethane was prepared by adding 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) (2.84 g, 19.3 mmol) to a biphasic solution (10 ml 40% KOH/5 ml ether) and stirring at 0° C. for 5 minutes. The biphasic solution was cooled to −78° C. to freeze the aqueous layer. The diazomethane solution was decanted into a vial containing a solution of (6) (0.841 g, 1.93 mmol) in 5 ml of ether. Palladium (II) acetate (43.3 mg, 0.193 mmol) was added and the reaction was stirred for 30 min. This procedure of adding diazomethane solution followed by palladium catalyst was repeated 2 more times to produce a greater yield. Dichloromethane (10 ml) was added followed by sat. NaHCO3 (5 ml). The catalyst was filtered off and the organic layer was isolated and dried over sodium sulfate. The organic layer was concentrated in vacuo and purified via column chromatography using ethyl acetate/hexane gradients to yield (2S,4R)-4-(tert-butyldimethylsilyloxy)-2-cyclopropyl-1-(4-(trifluoromethyl)phenylsulfonyl)pyrrolidine (10) (0.520 g, 60%) as a clear oil. This was a mixture of (R) (64%) and (S) (36%) isomers. MS m/z 449.1 (M+H)+; retention time=7.069 min ((R)-isomer) and 7.292 ((S) isomer); method [10].

Provenance & Evidence