Dimethylformamide → 2,2,2-Trifluoro-N-((1R,4R)-4-hydroxy-1,2,3,4-tetrahydronaphthalen-1-yl)acetamide

Temperature

50 °C

(R)-2,2,2-Trifluoro-N-(4-oxo-1,2,3,4-tetrahydronaphthalen-1-yl)acetamide (0.5 g), RuCl[(R,R)-Tsdpen(p-cymene)] and DMF (25 mL) were added to a flask that was purged with argon (catalyst prepared using procedure from Org Syn, Vol 82, pg 10-17, note 5). Triethylamine and HCOOH were added and the reaction mixture was stirred at 50° C. overnight. Further addition of catalyst (0.06 g), TEA (0.4 mL) and HCOOH (0.12 mL) were required to drive the reaction to completion after continued heating at 50° C. for an additional 6-8 hr. The reaction mixture was cooled to room temp, diluted with 150 mL EtOAc, and washed with 20 mL distilled water. The organic phase was dried over MgSO4 and concentrated in vacuo, and purified by column chromatography (eluting with 1% MeOH/DCM), to give 0.417 g (83%) of the titled compound. 1H-NMR (300 MHz, CDCl3) □ 7.5 (d, 1H), 7.3 (m, 2H), 7.2 (d, 1H), 6.4 (broad s, 1H), 5.3 (q, 1H), 4.8 (d, 1H), 2.4 (m, 1H), 2.2 (m 1H), 1.8 (m, 2H) ppm.

1. customwas purged with argon (catalyst prepared using procedure from Org Syn, Vol 82, pg 10-17, note 5)
2. additionTriethylamine and HCOOH were added
3. additionFurther addition of catalyst (0.06 g), TEA (0.4 mL) and HCOOH (0.12 mL)
4. customthe reaction to completion
5. temperatureafter continued heating at 50° C. for an additional 6-8 hr
6. temperatureThe reaction mixture was cooled to room temp
7. washwashed with 20 mL
8. distillationdistilled water
9. dry with materialThe organic phase was dried over MgSO4
10. concentrationconcentrated in vacuo
11. custompurified by column chromatography (eluting with 1% MeOH/DCM)

ORD record

ord-c889f623c3cf4292a6965b56010c746e

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07884109B2