反応 #56794

反応方程式

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

収率 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

収率 78.6%

溶媒

DMSO

反応条件

後処理

1. 1
   温度The reaction mixture was heated to 1000 C under nitrogen for 1 hour
2. 2
   温度the reaction mixture was heated to 1000 C under nitrogen for 1 hour
3. 3
   温度The reaction mixture was cooled
4. 4
   その他partitioned between ethyl ether and water
5. 5
   洗浄The organic layer was washed with saturated aqueous sodium bicarbonate solution and brine
6. 6
   乾燥dried with sodium sulfate
7. 7
   ろ過filtered
8. 8
   濃縮concentrated
9. 9
   その他The crude product was purified with a flash chromatography on silica gel
10. 10
    洗浄eluted with 50% ethyl acetate in hexane

実験手順

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 ).

出典