(-)-3-Hydroxytetrahydrofuran → HCID 118036326, compound

(R)-tetrahydrofuran-3-ol (161 mg, 1.82 mmol) was treated at room temperature with KHMDS (1 M in THF, 1.09 ml, 1.09 mmol). The reaction mixture was stirred for 2 min. Then, the mixture was added to a solution of 6-amino-4-fluoronicotinonitrile (intermediate 21, 50 mg, 0.365 mmol) in NMP (0.5 ml). The resulting dark brown solution was stirred at room temperature for 1 h 50 min. The reaction mixture was quenched with sat. aq. NH4Cl and extracted 2× with EtOAc. The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude material was purified by normal phase chromatography (4 g silica gel cartridge, DCM/(DCM/(1 M NH3 in MeOH) 9/1) 100:0 to 0:100) to give the title compound as a brown solid. (UPLC-MS 3) tR 0.48 min; ESI-MS 206.1 [M+H]+.

1. stirringThe resulting dark brown solution was stirred at room temperature for 1 h 50 min
2. customThe reaction mixture was quenched with sat. aq. NH4Cl
3. extractionextracted 2× with EtOAc
4. dry with materialThe combined organic layers were dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe crude material was purified by normal phase chromatography (4 g silica gel cartridge, DCM/(DCM/(1 M NH3 in MeOH) 9/1) 100:0 to 0:100)

ORD record

ord-91c8474f3ac641a4935d1b5604690eac

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09266883B2