Trimethyl borate → (1S,4S)-1,4-bis(4-chloro-3-nitrophenyl)butane-1,4-diol

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Reaction Conditions

Reaction Steps

(R)-(+)-alpha,alpha-diphenyl-2-pyrrolidinemethanol (1.08 g, 4.28 mmol) was dissolved in 70 mL of THF at ambient temperature in a dry flask under nitrogen and the trimethyl borate (650 uL, 5.54 mmol) was added dropwise. The resulting solution was stirred for 1 hr. The solution was cooled in a cold bath to ˜10° C. and the N,N-diethylaniline borane (9.18 mL, 51.6 mmol) was added dropwise with some bubbling. After 15 min, this solution was transferred to an addition funnel and added dropwise to 1,4-bis(4-chloro-3-nitrophenyl)butane-1,4-dione (Example 109B) (10.0 g, 25.2 mmol) suspended in 200 mL of THF and cooled to ˜10° C. Bubbling was observed. After the addition, mixture was stirred at ambient temperature for 4 hours. The mixture was cooled in an ice bath and 30 mL MeOH was added dropwise till bubbling stopped, then the mixture was let stir at ambient temperature for 30 min. The mixture was filtered to get rid of a trace of insoluble unreacted SM. The filtrate was concentrated, poured into 1 M HCl and extracted into ethyl acetate, dried over sodium sulfate; concentrated to give the title compound (9.9 g, 99%) as a yellow waxy solid. Chiral HPLC e.e. >99.9% (RR diol was undetectable). 1H NMR (400 MHz, DMSO-d6) δ 7.94 (d, J=1.9 Hz, 2H), 7.69 (d, J=8.4 Hz, 2H), 7.60 (dd, J=8.4, 1.9 Hz, 2H), 4.65 (m, 2H), 1.62 (m, 4H).

Provenance & Evidence