Triethylamine → 2-(2-Ethynylphenyl)acetamide

To a nitrogen de-gassed solution of 2-(2-iodophenyl)acetamide (I38) (1.75 g, 6.70 mmol) in dry THF (50 mL) and dry DMF (10 mL) was added Pd(PPh3)4 (0.194 g, 0.168 mmol) and Cu(I)I (0.064 g, 0.34 mmol), triethylamine (3.27 mL, 23.5 mmol). The mixture was stirred for 10 minutes and TMS-acetylene (1.52 mL, 10.7 mmol) was added. The reaction mixture was then stirred at room temperature for 18 hours, concentrated in vacuo and purified by silica gel chromatography (Biotage Isolera, 40 g Si cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) to give a beige solid. This material was dissolved in dry THF (25 mL) under an atmosphere of nitrogen and TBAF (1.0 M in THF, 2.805 mL, 2.805 mmol) was added dropwise at 0° C. The solution was stirred at this temperature for 1 hour and 15 minutes after which water (5 mL) was added. The reaction mixture was concentrated in vacuo and diluted with EtOAc (100 mL) and sat. aq. NaHCO3 (100 mL). The layers were separated and aqueous layer was extracted with EtOAc (100 mL), the organic layers were combined and washed with water (100 mL), brine (100 mL), dried (MgSO4), filtered and concentrated in vacuo to give the crude product. The material was purified by silica gel chromatography (Biotage Isolera, 40 g Si cartridge, 0-100% EtOAc in petroleum benzine 40-60° C., then 0-20% methanol in EtOAc) to give the title compound (I39) (0.239 g, 22% yield over 2 steps) as a beige solid; 1H NMR (400 MHz, d6-DMSO) δ 7.21 (dd, J=7.6, 1.1 Hz, 1H), 7.18-7.05 (m, 3H), 7.04-6.98 (m, 1H), 6.70 (s, 1H), 4.08 (s, 1H), 3.36 (s, 2H). LCMS Method C: rt 4.71 min; m/z 160.2 [M+H]+.

1. stirringThe reaction mixture was then stirred at room temperature for 18 hours
2. concentrationconcentrated in vacuo
3. custompurified by silica gel chromatography (Biotage Isolera, 40 g Si cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.)
4. customto give a beige solid
5. additionwas added
6. concentrationThe reaction mixture was concentrated in vacuo
7. additiondiluted with EtOAc (100 mL) and sat. aq. NaHCO3 (100 mL)
8. customThe layers were separated
9. extractionaqueous layer was extracted with EtOAc (100 mL)
10. washwashed with water (100 mL), brine (100 mL)
11. dry with materialdried (MgSO4)
12. filtrationfiltered
13. concentrationconcentrated in vacuo
14. customto give the crude product
15. customThe material was purified by silica gel chromatography (Biotage Isolera, 40 g Si cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.

ORDレコード

ord-e3b5d41a04ca45878d0020ca078b3453

出典データセット

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09421205B2