Carbon Dioxide → 1,1-Dimethylethyl 4-[3-[(4-methoxyphenyl)methyl]-1,2,4-oxadiazol-5-yl]-1-piperidinecarboxylate

HRID 1992066ノート

反応式

HRID 1992066 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.C(=O)=O.O/[N:33]=[C:34](\[NH2:44])/[CH2:35][C:36]1[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=1>CN(C=O)C.CCOC(C)=O>[CH3:43][O:42][C:39]1[CH:40]=[CH:41][C:36]([CH2:35][C:34]2[N:33]=[C:14]([CH:11]3[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]3)[O:16][N:44]=2)=[CH:37][CH:38]=1

参加物

7

反応物 4

HCID 280Carbon DioxideHCID 682631,1'-CarbonyldiimidazoleHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 5356867N-Hydroxy-2-(4-methoxy-phenyl)-acetamidine

生成物 1

HCID 587285131,1-Dimethylethyl 4-[3-[(4-methoxyphenyl)methyl]-1,2,4-oxadiazol-5-yl]-1-piperidinecarboxylate

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
70 °C

実験手順

1-(tert-Butoxycarbonyl)piperidine-4-carboxylic acid (2.29 g, 10.0 mmoles) in 10 mL DMF was treated with 1,1′-carbonyldiimidazole (1.62 g, 10 mmoles, 1 eq.) at ambient temperature for 30 min until CO2 evolution ceased. (1Z)-N′-hydroxy-2-(4-methoxyphenyl)ethanimidamide [J. Med. Chem., 36(11), 1529 (1993)] (10.0 mmoles, 1 eq.) was dissolved in 5 mL DMF and added to the reaction mixture. The reaction mixture was heated at 70° C. for 6 h then at 120° C. for an additional 6 h. The reaction mixture was diluted with EtOAc and washed successively with water, 1N citric acid, saturated aqueous NaHCO3, and brine. The organic phase was isolated, dried over MgSO4, filtered and concentrated to give the title compound as an amber oil. 1H NMR (300 MHz, CDCl3) δ 7.26 (d, 2H, J=8.5 Hz), 6.88 (d, 2H, J=8.5 Hz), 4.10 (m, 2H), 4.00 (s, 2H), 3.80 (s, 3H), 3.08 (m, 1H), 2.97-2.90 (m, 2H), 2.04 (m, 2H), 1.87-1.73 (m, 2H), 1.47 (s, 9H). ES-LCMS m/z 395.99 (M+Na).

後処理

  1. additionadded to the reaction mixture
  2. washwashed successively with water, 1N citric acid, saturated aqueous NaHCO3, and brine
  3. customThe organic phase was isolated
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

出典と根拠

ORDレコード
ord-6280f2a4d5f64ec7a1b0a24737615dda
出典データセット
uspto-grants-2010_01
特許番号
US07645771B2

反応ノート

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