Ethyl Acetate → HCID 89995490、化合物

HRID 1487297ノート

反応式

HRID 1487297 の反応式
[Br:1][C:2]1[N:3]=[C:4]([C:15]([O:17]CC)=O)[N:5]([NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH:6]=1.CC(C)([O-])C.[K+].[C:26]([O:29][CH2:30][CH3:31])(=[O:28])[CH3:27]>C1COCC1>[Br:1][C:2]1[N:3]=[C:4]([C:15](=[O:17])[CH2:27][C:26]([O:29][CH2:30][CH3:31])=[O:28])[N:5]([NH:7][C:8]([O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:9])[CH:6]=1

参加物

5

反応物 3

HCID 8857Ethyl AcetateHCID 23665647Potassium tert-butoxideHCID 89995466HCID 89995466、化合物

生成物 1

HCID 89995490HCID 89995490、化合物収率 70.3%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

To a solution of ethyl 4-bromo-1-((tert-butoxycarbonyl)amino)-1H-imidazole-2-carboxylate (1.90 g, 5.69 mmol) in THF (4.4 ml) at 0° C., was added dropwise a cold (pre-cooled at 0° C.) 1M THF solution of potassium tert-butoxide (17.06 ml, 17.06 mmol). The reaction was stirred at 0° C. for 5 minutes. Dry ethyl acetate (1.410 ml, 14.40 mmol), which was pre-cooled at 0° C., was added dropwise. Stirring was continued at 0° C. for 15 minutes. The ice bath was removed. The reaction was stirred at room temperature for 2 hrs, becoming a darker yellow suspension. The reaction was cooled to 0° C., and treated with 1.0 N HCl via dropwise addition until complete dissolution of the suspension. The reaction was concentrated to half volume under reduced pressure, and diluted with ethyl acetate. The solution was adjusted to basic by addition of 1.0 N NaOH. The aq. layer was back extracted with ethyl acetate (3×). The ethyl acetate extracts were combined, dried with sodium sulfate, filtered, and concentrated to give ethyl 3-(4-bromo-1-((tert-butoxycarbonyl)amino)-1H-imidazol-2-yl)-3-oxopropanoate (1.502 g, 4.00 mmol, 70% yield) as a pale yellow solid. LCMS (Method B) m/z 376.1 [M+1], Br-pattern; HPLC (Method B): Rt 2.961 min. 1H NMR (400 MHz, MeOD, enoate form) δ 7.51 (s, 1H), 4.18 (q, J=7.3 Hz, 2H), 4.00 (s, 1H), 3.97 (s, 1H), 1.49 (br. s., 9H), 1.25 (t, J=7.2 Hz, 3H).

後処理

  1. additionwas added dropwise
  2. stirringStirring
  3. waitwas continued at 0° C. for 15 minutes
  4. customThe ice bath was removed
  5. stirringThe reaction was stirred at room temperature for 2 hrs
  6. temperatureThe reaction was cooled to 0° C.
  7. additiontreated with 1.0 N HCl via dropwise addition until complete dissolution of the suspension
  8. concentrationThe reaction was concentrated to half volume under reduced pressure
  9. additiondiluted with ethyl acetate
  10. additionbasic by addition of 1.0 N NaOH
  11. extractionThe aq. layer was back extracted with ethyl acetate (3×)
  12. dry with materialdried with sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated

出典と根拠

ORDレコード
ord-c9f44eb339a3438abeae1ac6b965c986
出典データセット
uspto-grants-2016_08
特許番号
US09428511B2

反応ノート

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