Triethylamine → HCID 57764577, compound

Temperature

80 °C

To a mixture of 4-(4-bromobenzyl)morpholine (4.18 g, 16.3 mmol) and 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (3 mL, 17.7 mmol, 1.1 eq.) and toluene (30 mL) in a 20 mL microwave vial was added Et3N (4.56 mL, 32.4 mmol, 2 eq.), followed by Pd(PtBu3)2 (83 mg, 0.16 mmol, 1 mol %). The resulting mixture was purged with argon, then capped and heated at 80° C. oil bath for 1 h. After cooling to rt, the reaction was diluted with half saturated NaHCO3 (40 mL) and the product was extracted with EtOAc (2×60 mL). The organic layer was dried (Na2SO4) and the solvent was evaporated in vacuo. Trituration with hexane and sonication provided a solid that was collected by suction filtration (white solid, 2.55 g). After evaporation of the solvent in vacuo, the residue solidified and a second crop of crystals was obtained by suction filtration from a small amount of hexane (pale yellow crystals, 0.22 g). Evaporation of the mother liquor provided a yellow liquid which was purified using Biotage Isolera (20-80% EtOAc in hexane, SNAP-50 g column) to give a third portion of the product (yellow solid, 1.58 g; total yield 4.35 g, 71%). 1H NMR (400 MHz, CDCl3) δ 7.45 (d, J=8.0 Hz, 2H), 7.40 (d, J=18.4 Hz, 1H), 7.31 (d, J=8.0 Hz, 2H), 6.16 (d, J=18.0 Hz, 1H), 3.72 (t, J=4.4 Hz, 4H), 3.50 (s, 2H), 2.47-2.42 (m, 4H), 1.32 (s, 12H); MS ESI 330.1 [M+H]+, calcd for [C19H28BNO3+H]+ 330.2.

1. customThe resulting mixture was purged with argon
2. customcapped
3. temperatureAfter cooling to rt
4. additionthe reaction was diluted with half saturated NaHCO3 (40 mL)
5. extractionthe product was extracted with EtOAc (2×60 mL)
6. dry with materialThe organic layer was dried (Na2SO4)
7. customthe solvent was evaporated in vacuo
8. customTrituration with hexane and sonication
9. customprovided a solid
10. filtrationthat was collected by suction filtration (white solid, 2.55 g)
11. customAfter evaporation of the solvent in vacuo
12. customthe residue solidified and a second crop of crystals was obtained by suction filtration from a small amount of hexane (pale yellow crystals, 0.22 g)
13. customEvaporation of the mother liquor
14. customprovided a yellow liquid which
15. customwas purified
16. customto give a third portion of the product (yellow solid, 1.58 g; total yield 4.35 g, 71%)

ORD record

ord-008cc202a76f47a3bb4d3a66f81b719f

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08921545B2