2-Methyl-2-butanol → (S)-5-Bromo-2-(2-(trifluoromethyl)pyrrolidin-1-yl)pyrimidine

Temperature

85 °C

A flask was charged with 5-bromo-2-chloropyrimidine (36.62 g, 189 mmol), (S)-2-(trifluoromethyl)pyrrolidine (34.2 g, 246 mmol), potassium carbonate (39.2 g, 284 mmol)) and t-amyl alcohol (189 mL). The reaction mixture was stirred at 85° C. for 72 hours. The reaction mixture was then filtered over Celite®, washed with CH2Cl2 (2×) and concentrated in vacuo. The crude residue was redissolved in CH2Cl2 and washed with water and brine. The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo to give crystalline solids. The solids were washed with cold water (3×) and triturated with toluene to give the title product as pale orange crystals, 43.4 g (147 mmol, 77%); 1H NMR (300 MHz, DMSO-d6)_8.58 (s, 2H), 5.06-4.83 (m, 1H), 3.71-3.44 (m, 2H), 10 2.30-1.89 (m, 4H); m/z found [M+H]+=295.99.

1. filtrationThe reaction mixture was then filtered over Celite®
2. washwashed with CH2Cl2 (2×)
3. concentrationconcentrated in vacuo
4. dissolutionThe crude residue was redissolved in CH2Cl2
5. washwashed with water and brine
6. dry with materialThe combined organic layers were dried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customto give crystalline solids
10. washThe solids were washed with cold water (3×)
11. customtriturated with toluene

ORD record

ord-e6f94d2818764381ae0a8b1a2b01a0b9

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09394308B2