반응 #56794

반응 방정식

sodium thiomethoxide

compound 10a

3-[2(R)-tert-butoxycarbonylamino-2-phenylethyl]-5-(2-fluoro-3-methoxyphenyl)-1-[2,6-difluorobenzyl]-6-methyl-pyrimidine-2,4(1H,3H)-dione

sodium thiomethoxide

→

compound 10b

수율 78.6%

3-[2(R)-tert-butoxycarbonylamino-2-phenylethyl]-5-(2-fluoro-3-methoxylphenyl)-1-[2-fluoro-6-methylthiobenzyl]-6-methyl-pyrimidine-2,4(1H,3H)-dione

수율 78.6%

용매

DMSO

반응 조건

후처리

1. 1
   온도The reaction mixture was heated to 1000 C under nitrogen for 1 hour
2. 2
   온도the reaction mixture was heated to 1000 C under nitrogen for 1 hour
3. 3
   온도The reaction mixture was cooled
4. 4
   기타partitioned between ethyl ether and water
5. 5
   세척The organic layer was washed with saturated aqueous sodium bicarbonate solution and brine
6. 6
   건조dried with sodium sulfate
7. 7
   여과filtered
8. 8
   농축concentrated
9. 9
   기타The crude product was purified with a flash chromatography on silica gel
10. 10
    세척eluted with 50% ethyl acetate in hexane

실험 절차

To a solution of compound 10a (33 g, 56 mmol) in dry DMSO (100 mL) was added sodium thiomethoxide (4.0 g, 56 mmol) under nitrogen. The reaction mixture was heated to 1000 C under nitrogen for 1 hour. Another 0.28 eq. of sodium thiomethoxide (1.1 g, 16 mmol) was added, and the reaction mixture was heated to 1000 C under nitrogen for 1 hour. The reaction mixture was cooled and partitioned between ethyl ether and water. The organic layer was washed with saturated aqueous sodium bicarbonate solution and brine, dried with sodium sulfate, filtered and concentrated. The crude product was purified with a flash chromatography on silica gel eluted with 50% ethyl acetate in hexane to yield compound 10b as a pale yellow solid (27 g, 44 mmol, 78%). HPLC-MS (CI) m/z=524.1 (M+H+-Boc), tR=3.134 (method 4). 1H NMR (CDCl3): 1.38 (s, 9H), 2.07 (s, 3H), 2.51 (s, 3H), 3.90 (s, 3H), 4.07-4.13 (m, 1H), 4.29-4.39 (m, 1H), 5.30-5.53 (m, 2H), 5.79-5.85 (m, 1H), 6.80-6.91 (m, 2H), 6.70 (dd, 1H), 7.06-7.15 (m, 2H), 7.22-7.41 (m, 6h ).

출처