Sodium Hydroxide → 3-[5-(2-Fluoro-phenyl)-1H-benzimidazol-2-yl]-1,8-dioxa-2-aza-spiro[4.5]dec-2-ene

HRID 1518146ノート

反応式

HRID 1518146 の反応式
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15]([C:17]2[CH2:21][C:20]3([CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[O:19][N:18]=2)=O)=[C:10]([N+:27]([O-])=O)[CH:9]=1.[OH-].[Na+]>C(O)(=O)C.[Fe]>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][C:11]2[NH:14][C:15]([C:17]3[CH2:21][C:20]4([CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[O:19][N:18]=3)=[N:27][C:10]=2[CH:9]=1

参加物

5

反応物 2

HCID 14798Sodium HydroxideHCID 592800831,8-Dioxa-2-aza-spiro[4.5]dec-2-ene-3-carboxylic acid (2'-fluoro-3-nitro-biphenyl-4-yl)-amide

生成物 1

HCID 1785056043-[5-(2-Fluoro-phenyl)-1H-benzimidazol-2-yl]-1,8-dioxa-2-aza-spiro[4.5]dec-2-ene収率 86%

試薬・触媒・溶媒 2

HCID 23925Iron触媒HCID 176Acetic Acid溶媒

反応条件

温度
100 °C

実験手順

A solution of 1,8-dioxa-2-aza-spiro[4.5]dec-2-ene-3-carboxylic acid (2′-fluoro-3-nitro-biphenyl-4-yl)-amide (131 mg, 0.327 mmol, as prepared in the previous step) in glacial acetic acid (10 mL) was treated with Fe powder (91.2 mg, 1.36 mmol) and heated to 100° C. under a reflux condenser for 4 h. The pH of the mixture was adjusted to 7 with 6M aq NaOH. The resulting aqueous mixture was extracted three times with EtOAc (50 mL), and the combined organic layers were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 40-g Sepra Si 50 SPE column (Isco system: Flow rate=25 mL/min; Eluent=EtOAc/hexanes, 1:9 v/v for 10 min, then 1:9 to 2:3 v/v over 40 min) to afford the title compound (98.8 mg, 86%) as an off-white solid. 1H-NMR (400 MHz, CDCl3) δ: 7.78-7.90 (m, 1H), 7.55-7.68 (m, 1H), 7.46-7.54 (m, 2H), 7.29-7.39 (m, 1H), 7.14-7.26 (m, 2H), 3.97 (ddd, J=11.7, 8.1, 3.4 Hz, 2H), 3.70-3.81 (m, 2H), 3.47 (s, 2H), 1.99-2.08 (m, 3H), 1.87-1.98 (m, 2H). Mass Spectrum (LCMS, ESI pos.): Calcd. for C20H18FN3O2: 352.1 (M+H). found: 352.2.

後処理

  1. extractionThe resulting aqueous mixture was extracted three times with EtOAc (50 mL)
  2. dry with materialthe combined organic layers were dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified on a 40-g Sepra Si 50 SPE column (Isco system

出典と根拠

ORDレコード
ord-249d76552c9c4485aeb02267ce797a03
出典データセット
uspto-grants-2012_07
特許番号
US08232409B2

反応ノート

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