Methyl iodide → (2S,4S)-1-tert-butyl 2-methyl 4-(methoxymethyl)pyrrolidine-1,2-dicarboxylate

HRID 590661ノート

反応式

HRID 590661 の反応式
[OH:1][CH2:2][C@@H:3]1[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@H:5]([C:15]([O:17][CH3:18])=[O:16])[CH2:4]1.[C:19](C1C=CC=C(C(C)(C)C)N=1)(C)(C)C.CI>C(Cl)Cl.C(S([O-])(=O)=O)(F)(F)F.[Ag+]>[CH3:19][O:1][CH2:2][C@@H:3]1[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:13])([CH3:14])[CH3:12])=[O:9])[C@H:5]([C:15]([O:17][CH3:18])=[O:16])[CH2:4]1

参加物

6

反応物 3

HCID 6328Methyl iodideHCID 685102,6-Di-tert-butylpyridineHCID 696750381-(1,1-Dimethylethyl) 2-methyl (2S,4S)-4-(hydroxymethyl)-1,2-pyrrolidinedicarboxylate

生成物 1

HCID 69675330(2S,4S)-1-tert-butyl 2-methyl 4-(methoxymethyl)pyrrolidine-1,2-dicarboxylate収率 78%

試薬・触媒・溶媒 2

HCID 76223Silver(I) trifluoromethanesulfonate触媒HCID 6344Dichloromethane溶媒2 回

反応条件

温度
0 °C

実験手順

To a solution of (2S,4S)-1-tert-butyl 2-methyl 4-(hydroxymethyl)pyrrolidine-1,2-dicarboxylate (2.57 g, 9.9 mmol) in CH2Cl2 (50 mL) was added AgOTf (4.07 g, 15.8 mmol) and 2,6-di-tert-butylpyridine (4.4 mL, 19.8 mmol). The reaction mixture was cooled to 0° C. (external temperature, ice bath) and MeI (0.98 mL, 15.8 mmol) was slowly added. The resulting slurry was stirred at 0° C. for 1.5 h and at room temperature for 1.5 h. The slurry was diluted with CH2Cl2 and filtered through celite. The filtrate was concentrated to dryness, dissolved in Et2O, and washed with HCl (1N) and brine. The aqueous layers were backextracted with Et2O and the combined organic layers were dried over Na2SO4 and concentrated. The crude oil was purified by silica gel chromatography (10% to 75% to 100% EtOAc/Hexanes) to provide (2S,4S)-1-tert-butyl 2-methyl 4-(methoxymethyl)pyrrolidine-1,2-dicarboxylate (2.11 g, 78%). 1H-NMR: 400 MHz, (CDCl3) δ: (mixture of rotomers, major reported) 4.20 (t, 1H), 3.71 (s, 3H), 3.67 (m, 1H), 3.34 (m, 2H), 3.30 (s, 3H), 3.16 (t, 1H), 2.43 (m, 2H), 1.74 (m, 1H), 1.38 (s, 9H).

後処理

  1. additionwas slowly added
  2. filtrationfiltered through celite
  3. concentrationThe filtrate was concentrated to dryness
  4. dissolutiondissolved in Et2O
  5. washwashed with HCl (1N) and brine
  6. dry with materialthe combined organic layers were dried over Na2SO4
  7. concentrationconcentrated
  8. customThe crude oil was purified by silica gel chromatography (10% to 75% to 100% EtOAc/Hexanes)

出典と根拠

ORDレコード
ord-a1d276a3e2ee4f51ae07d376d06dfbc0
出典データセット
uspto-grants-2016_01
特許番号
US09233974B2

反応ノート

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