Pilocarpine Hydrochloride → racemic 2,2,2-trifluoro-N-(3-hydroxy-6-methyl-2,3-dihydro-1H-inden-1-yl)acetamide

Step BJ (1): L-Selectride (1 M/THF, 18.5 mL, 18.5 mmol) was added dropwise (over 30 min) to a solution of 2,2,2-trifluoro-N-(6-methyl-3-oxo-2,3-dihydro-1H-inden-1-yl)acetamide [Quermonne, M. A.; Dallemagne, P.; Louchahi-Raoul, J.; Pilo, J. C.; Rault, S.; Robba, M. Eur. J. Med. Chem. 1992, 27, 961-965] (3.97 g, 15.4 mmol) in THF (80 mL) at −78° C. After 2 hr at −78° C., the reaction mixture was quenched with saturated aqueous NH4Cl solution (2 mL) and allowed to warm to rt. The crude mixture was concentrated in vacuo. The residue was dissolved in EtOAc and washed with saturated aqueous NaHCO3 solution followed by brine. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo to afford 3.4 g (85% yield) of racemic 2,2,2-trifluoro-N-(3-hydroxy-6-methyl-2,3-dihydro-1H-inden-1-yl)acetamide. LC-MS (M+H)+=260.091H NMR (500 MHz, CDCl3) δ 9.16-9.12 (t, 1H) 7.31-7.29 (m, 1H) 7.02 (m, 1H) 6.94 (s, 1H) 4.98 (t, 1H) 4.10 (bs, 2H) 2.38-2.28 (m, 4H) 2.07-2.01 (m, 1H).

1. customat −78° C
2. customthe reaction mixture was quenched with saturated aqueous NH4Cl solution (2 mL)
3. concentrationThe crude mixture was concentrated in vacuo
4. dissolutionThe residue was dissolved in EtOAc
5. washwashed with saturated aqueous NaHCO3 solution
6. dry with materialThe organic layer was dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo

ORD record

ord-af991e36019d4389b9ecf71bbde71478

Source dataset

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07772221B2