1-benzyloxymethyl-1H-benzimidazole → (1-benzyloxymethyl-1H-benzimidazol-2-yl)-(3-bromothiophen-2-yl)methanone

HRID 2078678ノート

反応式

HRID 2078678 の反応式
[CH2:1]([O:8][CH2:9][N:10]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[N:12]=[CH:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.CON(C)[C:27]([C:29]1[S:30][CH:31]=[CH:32][C:33]=1[Br:34])=[O:28].CCOCC.CCCCCCC>O1CCCC1>[CH2:1]([O:8][CH2:9][N:10]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[N:12]=[C:11]1[C:27]([C:29]1[S:30][CH:31]=[CH:32][C:33]=1[Br:34])=[O:28])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

6

反応物 4

HCID 113223751-benzyloxymethyl-1H-benzimidazoleHCID 21897273Diethylether heptaneHCID 576374043-bromo-N-methoxy-N-methylthiophene-2-carboxamideHCID 178418339Butyllithium

生成物 1

HCID 57637380(1-benzyloxymethyl-1H-benzimidazol-2-yl)-(3-bromothiophen-2-yl)methanone

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

To a stirred solution of 1-benzyloxymethyl-1H-benzimidazole (648 mg, 2.72 mmol, Example 1B) in tetrahydrofuran (15 mL) at −78° C. under nitrogen is added n-butyllithium (1.30 mL of a 2.5 M solution in hexanes, 3.25 mmol) over 5 minutes and the resulting yellow solution is stirred at −78° C. After 25 minutes, a solution of 3-bromo-thiophene-2-carboxylic acid methoxy-methyl-amide (680 mg, 2.72 mmol, Example 1A) in tetrahydrofuran (10 mL) is added over 15 minutes and the reaction stirred at −78° C. After 1 hour the reaction is warmed to ambient temperature and stirred for an additional 2 hours. The reaction is quenched with saturated ammonium chloride and the mixture extracted with ethyl acetate. The organic layer is washed with water and brine successively, dried over magnesium sulfate, and concentrated under reduced pressure to a yellow oil. The crude material is chromatographed on silica, eluting with 40% ethyl acetate/heptane, to give the product. Trituration with ether/heptane affords (1-benzyloxymethyl-1H-benzimidazol-2-yl)-(3-bromothiophen-2-yl)methanone as an off-white powder; TLC Rf 0.52 (silica, 1:1 ethyl acetate/heptane); LC/MS: (M+H 427.0, RT=3.84 minutes); 1H NMR [(CD3)2SO), 300 MHz]: δ 8.18 (d, 1H, 5.2 Hz), 7.90-7.82 (m, 2H), 7.55-7.50 (m, 1H), 7.45-7.38 (m, 2H), 7.25-7.17 (m, 5H), 6.13 (s, 2H), 4.58 (s, 2H).

後処理

  1. stirringthe reaction stirred at −78° C
  2. temperatureAfter 1 hour the reaction is warmed to ambient temperature
  3. stirringstirred for an additional 2 hours
  4. customThe reaction is quenched with saturated ammonium chloride
  5. extractionthe mixture extracted with ethyl acetate
  6. washThe organic layer is washed with water and brine successively
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure to a yellow oil
  9. customThe crude material is chromatographed on silica
  10. washeluting with 40% ethyl acetate/heptane
  11. customto give the product

出典と根拠

ORDレコード
ord-59f44f7411734aa7858b021fad251b3c
出典データセット
uspto-grants-2011_04
特許番号
US07928231B2

反応ノート

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