Diisopropylamine → HCID 69940220、化合物

温度

-78 °C

To a stirred solution of iPr2NH (0.31 mL, 2.24 mmol) in THF (10 mL) at −78° C. under nitrogen atmosphere was added 2.5M n-BuLi in THF solution (0.75 mL, 1.86 mmol). The solution was stirred for 15 min at −78° C. and added to it in one portion was 2-iodo-5-chlorobenzyl alcohol (0.5 g, 1.86 mmol). This solution was stirred for 30 min at −78° C. then was concentrated in vacuo and placed under high vacuum for 1 h. The residue, under nitrogen atmosphere, was dissolved in THF (20 mL), cooled to −78° C., and 2.5M n-BuLi in THF solution (0.75 mL, 1.86 mmol) was added. This solution was stirred for 15 min at −78° C. and added drop wise was N-ethylidene-2-methyl-2-propanesulfinamide from the previous step (0.274 g, 1.86 mmol) dissolved in THF (5 mL). This solution was stirred for 30 min at −78° C. then was allowed to equilibrate to ambient temperature over 1 h. Saturated NH4Cl was added (3 mL), and the mixture was partitioned between EtOAc and water. The EtOAc layer was separated, dried over anhydrous Na2SO4, and filtered. The filtrate solvent was removed under reduced pressure and the residue was purified by flash silica gel chromatography eluting with a methanol in dichloromethane gradient (1% to 3% MeOH in 0.5% increments). After concentration of desired fractions in vacuo, the separate isomers of 2-(1-tert-butylsulfinamidylethyl)-5-chlorobenzyl alcohol were obtained as a yellow oils (isomer 1(less polar) 120 mg; HPLC RT=2.93 min, method A; LC-MS m/z=290.1; 1H NMR, 400 MHz, CDCl3, 7.38 ppm (s, 1H), 7.36 ppm (d, 1H), 7.28 ppm (dd, 1H), 4.86 ppm (d, 1H), 4.82 ppm (m, 1H), 4.54 ppm (d, 1H), 4.3 ppm (br s, 1H), 3.94 ppm (d, 1H), 1.54 ppm (d, 3H), 1.2 ppm (s, 9H); isomer 2(more polar) 38 mg; HPLC RT=2.69 min; LC-MS m/z=290.1; 1H NMR, 400 MHz, CDCl3 7.4 ppm (d, 1H), 7.365 ppm (d, 1H), 7.28 ppm (dd, 1H), 4.86 ppm (m, 1H), 4.78 ppm (dd, 1H), 4.64 ppm (dd, 1H), 3.67 ppm (br s, 1H), 3.65 ppm (d, 1H), 1.52 ppm (d, 3H), 1.18 ppm (s, 9H)).

1. additionadded to it in one portion
2. stirringThis solution was stirred for 30 min at −78° C.
3. concentrationthen was concentrated in vacuo
4. waitplaced under high vacuum for 1 h
5. dissolutionThe residue, under nitrogen atmosphere, was dissolved in THF (20 mL)
6. temperaturecooled to −78° C.
7. stirringThis solution was stirred for 15 min at −78° C.
8. stirringThis solution was stirred for 30 min at −78° C.
9. waitto equilibrate to ambient temperature over 1 h
10. customthe mixture was partitioned between EtOAc and water
11. customThe EtOAc layer was separated
12. dry with materialdried over anhydrous Na2SO4
13. filtrationfiltered
14. customThe filtrate solvent was removed under reduced pressure
15. customthe residue was purified by flash silica gel chromatography
16. washeluting with a methanol in dichloromethane gradient (1% to 3% MeOH in 0.5% increments)

ORDレコード

ord-663fa89a1658468288613566484a05df

出典データセット

uspto-grants-2003_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06515011B2