Methanol → HCID 60164156, compound

Temperature

35 °C

To (6-hydroxy-1-benzofuran-3-yl)acetic acid (2.80 g) and dichloro[(+)-1,2-bis((2R,5R)-2,5-diisopropylphosphorano)benzene]ruthenium (II)-N,N-dimethylformamide complex (2.1 mg) were added (1R)-1-phenylethylamine (1.77 g) and deaerated methanol (28 mL), and the mixture was stirred at 35° C. for 18 hr under a hydrogen atmosphere (0.85 MPa). The mixture was allowed to cool to room temperature, and concentrated under reduced pressure. To the concentrated residue were added ethanol (14 mL) and N,N-dimethylformamide (7.7 mL), and the mixture was dissolved by heating to 70° C. While maintaining the same temperature, diisopropyl ether (28 mL) was added dropwise. The mixture was cooled to 5° C. and stirred for 1 hr, and the solid was collected by filtration, washed with diisopropyl ether-methanol (4:1, 6 mL), and dried at 50° C. under reduced pressure to give a crude resultant product (3.58 g). To the crude product (3.00 g) were added ethanol (15 mL) and N,N-dimethylformamide (6 mL), and the mixture was dissolved by heating to 60° C. While maintaining the same temperature, diisopropyl ether (39 mL) was added dropwise, and the mixture was cooled to 5° C. The mixture was stirred at the same temperature for 2 hr, and the solid was collected by filtration, washed with diisopropyl ether-methanol (4:1, 6 mL), and dried at 50° C. under reduced pressure to give the title compound (2.66 g). 99.7% de. (high performance liquid chromatography conditions) column: CHIRALPAK AD-H (manufactured by DAICEL CHEMICAL INDUSTRIES, LTD.)

1. temperatureto cool to room temperature
2. concentrationconcentrated under reduced pressure
3. additionTo the concentrated residue were added ethanol (14 mL) and N,N-dimethylformamide (7.7 mL)
4. dissolutionthe mixture was dissolved
5. temperatureby heating to 70° C
6. temperatureWhile maintaining the same temperature, diisopropyl ether (28 mL)
7. additionwas added dropwise
8. temperatureThe mixture was cooled to 5° C.
9. stirringstirred for 1 hr
10. filtrationthe solid was collected by filtration
11. washwashed with diisopropyl ether-methanol (4:1, 6 mL)
12. customdried at 50° C. under reduced pressure
13. customto give a crude resultant product (3.58 g)
14. dissolutionthe mixture was dissolved
15. temperatureby heating to 60° C
16. additionwas added dropwise
17. temperaturethe mixture was cooled to 5° C
18. stirringThe mixture was stirred at the same temperature for 2 hr
19. filtrationthe solid was collected by filtration
20. washwashed with diisopropyl ether-methanol (4:1, 6 mL)
21. customdried at 50° C. under reduced pressure

ORD record

ord-e755841b17de4228bf7a1ac64e1a72e3

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952185B2