Diisopropylamine → HCID 66600372, compound

A solution of diisopropylamine (13.51 mL, 96 mmol) in tetrahydrofuran (66 mL) was treated with 2.0 M n-butyl lithium in hexane (48.2 mL, 96 mmol) at −40° C. and stirred for 1 h. The resulting LDA solution was cooled to −78° C. and a solution of 4-((6-fluoropyridin-3-yl)methyl)morpholine (15.767 g, 80 mmol) in THF (50 mL) was added via cannula over 20 min. The deep-red mixture was stirred at −78° C. for 1.5 h. A solution of triisopropyl borate (27.7 mL, 121 mmol) in THF (22 mL) was added slowly. The resulting mixture was stirred at −78° C. for 30 min and then the cooling bath was removed and the reaction mixture was allowed to warm to room temperature. The mixture was quenched with 1 N NaOH(aq) (50 mL) and stirred. The aqueous layer was separated and the organic layer was extracted with 1 N NaOH (2×20 mL). The combined aqueous layers were carefully acidified with 5 N HCl until acidic (pH 5 to about 6) and the resulting cloudy mixture was extracted with EtOAc (3×100 mL). The aqueous layer was lyophilized. The resulting residue was diluted with 1:1 MeOH/DCM and placed into a sonicator for 5 min. The mixture was filtered through a fine-fritted funnel The filtrate was concentrated to give 2-fluoro-5-(morpholinomethyl)pyridin-3-ylboronic acid (19.000 g, 79 mmol, 99% yield) as a tan oil. 1H NMR (400 MHz, d4-MeOH) δ 8.46 (s, 1H); 8.32 (d, J=6.06 Hz, 1H); 4.42 (s, 2H); 3.82-4.00 (m, 4H); 3.23-3.36 (m, 4H); 2.01 (s, 1H). m/z (ESI, +ve ion) 241.1 (M+H)+.

1. stirringThe deep-red mixture was stirred at −78° C. for 1.5 h
2. stirringThe resulting mixture was stirred at −78° C. for 30 min
3. customthe cooling bath was removed
4. customThe mixture was quenched with 1 N NaOH(aq) (50 mL)
5. stirringstirred
6. customThe aqueous layer was separated
7. extractionthe organic layer was extracted with 1 N NaOH (2×20 mL)
8. extractionthe resulting cloudy mixture was extracted with EtOAc (3×100 mL)
9. additionThe resulting residue was diluted with 1:1 MeOH/DCM
10. waitplaced into a sonicator for 5 min
11. filtrationThe mixture was filtered through a fine-fritted funnel The filtrate
12. concentrationwas concentrated

ORD record

ord-0eb8ebd6331a444984c3fc128da2ed6d

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08362241B2