Ammonium Chloride → (1-benzyloxymethyl-6-methoxy-1H-benzoimidazol-2-yl)-(3-bromo-thiophen-2-yl)-methanone

HRID 2078681ノート

反応式

HRID 2078681 の反応式
[CH2:1]([O:8][CH2:9][N:10]1[C:14]2[CH:15]=[C:16]([O:19][CH3:20])[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:29]([C:31]1[S:32][CH:33]=[CH:34][C:35]=1[Br:36])=[O:30].[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C.CCCCCCC>[CH2:1]([O:8][CH2:9][N:10]1[C:14]2[CH:15]=[C:16]([O:19][CH3:20])[CH:17]=[CH:18][C:13]=2[N:12]=[C:11]1[C:29]([C:31]1[S:32][CH:33]=[CH:34][C:35]=1[Br:36])=[O:30])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

7

反応物 4

HCID 25517Ammonium ChlorideHCID 576373451-benzyloxymethyl-6-methoxy-1H-benzoimidazoleHCID 576374043-bromo-N-methoxy-N-methylthiophene-2-carboxamideHCID 178418339Butyllithium

生成物 1

HCID 57637377(1-benzyloxymethyl-6-methoxy-1H-benzoimidazol-2-yl)-(3-bromo-thiophen-2-yl)-methanone収率 32.1%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 21899848Ethylacetate heptane溶媒

反応条件

温度
-78 °C

実験手順

To a stirred solution of 1-benzyloxymethyl-6-methoxy-1H-benzoimidazole (1.00 g, 3.72 mmol, Example 2A) in anhydrous tetrahydrofuran (15 mL) at −78° C. under nitrogen is added n-butyllithium (1.80 mL of a 2.5 M solution in hexanes, 4.5 mmol) over 8 minutes and the resulting yellow solution is stirred a −78° C. After 25 minutes, a solution of 3-bromo-thiophene-2-carboxylic acid methoxy-methyl-amide (1.03 g, 4.12 mmol) in tetrahydrofuran (10 mL) is added over 20 minutes, to the reaction at −78° C. The reaction is allowed to gradually warm to ambient temperature overnight. The reaction is poured into 10% aqueous ammonium chloride (75 mL) and the mixture extracted twice with ethyl acetate (50 mL). 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 30% ethyl acetate/heptane followed by 40% ethyl acetate/heptane, to give a waxy solid. Trituration with 25% ethyl acetate/heptane afforded 546 mg (32%) of (1-benzyloxymethyl-6-methoxy-1H-benzoimidazol-2-yl)-(3-bromo-thiophen-2-yl)-methanone, as a powder: TLC Rf 0.43 (silica, 40% ethyl acetate/heptane); LC/MS: (M+H 457, RT=3.85 minutes); 1H NMR [(CD3)2SO), 300 MHz]: δ 8.14 (d, 5.2 Hz, 1H), 7.76 (d, 9.0 Hz, 1H), 7.36 (d, 5.0 Hz, 1H), 7.29-7.20 (m, 6H), 7.04 (dd, 2.5, 9.0 Hz, 1H), 6.13 (s, 2H), 4.59 (s, 2H), 3.87 (s, 3H).

後処理

  1. temperatureto gradually warm to ambient temperature overnight
  2. extractionthe mixture extracted twice with ethyl acetate (50 mL)
  3. washThe organic layer is washed with water and brine successively
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure to a yellow oil
  6. customThe crude material is chromatographed on silica
  7. washeluting with 30% ethyl acetate/heptane
  8. customto give a waxy solid

出典と根拠

ORDレコード
ord-2e8b9a01aaa34f6baf5bd4959833669e
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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