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

Temperatur

10 °C

(R)-(+)-α,α-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 trimethyl borate (650 uL, 5.54 mmol) was added dropwise. The resulting solution was stirred for 1 hour. 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 minutes, this solution was transferred to an addition funnel and added dropwise to 1,4-bis(4-chloro-3-nitrophenyl)butane-1,4-dione (Intermediate 5B) (10.0 g, 25.2 mmol) suspended in 200 mL of THF and cooled to ˜10° C. Bubbling was observed. After the addition, the mixture was stirred at ambient temperature for 4 hours. The mixture was cooled in an ice bath and 30 mL or methanol was added dropwise until bubbling stopped, then the mixture was allowed to stir at ambient temperature for 30 minutes. The mixture was filtered to get rid of a trace of insoluble unreacted starting material. The filtrate was concentrated, poured into 1 M HCl and extracted into ethyl acetate, dried over sodium sulfate, and 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 ppm 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).

1. waitAfter 15 minutes
2. customthis solution was transferred to an addition funnel
3. temperaturecooled to ˜10° C
4. customBubbling
5. additionAfter the addition
6. stirringthe mixture was stirred at ambient temperature for 4 hours
7. temperatureThe mixture was cooled in an ice bath
8. addition30 mL or methanol was added dropwise
9. customuntil bubbling
10. stirringto stir at ambient temperature for 30 minutes
11. filtrationThe mixture was filtered
12. customto get
13. concentrationThe filtrate was concentrated
14. additionpoured into 1 M HCl
15. extractionextracted into ethyl acetate
16. dry with materialdried over sodium sulfate
17. concentrationconcentrated

ORD-Eintrag

ord-c81ebf2f5b2043e09d35d3659db455b6

Quelldatensatz

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08937150B2