1,2-Bis(2-iodoethoxy)ethane → Diethyl 1,1-difluoro-3-(2-(2-iodoethoxy)ethoxy)propylphosphonate

To a solution of diethyl difluoromethylphosphonate (1.0 equiv.) in THF (0.8 M) at −78° C. was slowly added a solution of LDA (2 M, 1.1 equiv.) in heptane/THF/ethylbenzene, and the mixture was vigorously stirred for 30 minutes. In a separate reaction flask, a solution of 1,2-bis(2-iodoethoxy)ethane (1.0 equiv.) in THF (0.8M) was cooled to −78° C. To this solution was transferred, by cannula, the freshly prepared alkyl lithium solution and the reaction mixture was allowed to stir for 1 hour at −78° C. At this point, the cooling bath was removed and the reaction mixture was allowed to warm to room temperature. The reaction mixture was then quenched with a 1 M aqueous solution of HCl. The resulting mixture was transferred to a separatory funnel and washed with CH2Cl2 three times. The combined organic layers were dried over anhydrous Na2SO4 and the volatiles were removed in vacuo. The resulting residue was purified by a COMBIFLASH® system (ISCO) using CH2Cl2 to provide diethyl 1,1-difluoro-3-(2-(2-iodoethoxy)ethoxy)propylphosphonate (I-1) as a yellow oil. 1H NMR (CDCl3): δ 4.23-4.31 (m, 4H), 3.75-3.80 (m, 4H), 3.60-3.67 (m, 4H), 3.26 (t, 2H), 2.33-2.50 (m, 2H), 1.38 (t, 6H).

1. customIn a separate reaction flask
2. stirringto stir for 1 hour at −78° C
3. customAt this point, the cooling bath was removed
4. customThe reaction mixture was then quenched with a 1 M aqueous solution of HCl
5. customThe resulting mixture was transferred to a separatory funnel
6. washwashed with CH2Cl2 three times
7. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
8. customthe volatiles were removed in vacuo
9. customThe resulting residue was purified by a COMBIFLASH® system (ISCO)

ORDレコード

ord-4c1c501c455c432cbcdd928e6a60695c

出典データセット

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09045470B2