三氟乙酸 → 4-(3-氟苯氧基)哌啶

HRID 906348笔记

反应方程式

HRID 906348 反应方程式
[F:1][C:2]1[CH:3]=[C:4]([O:8][CH:9]2[CH2:14][CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11][CH2:10]2)[CH:5]=[CH:6][CH:7]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([O:8][CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH:5]=[CH:6][CH:7]=1

参与物

4

反应物 2

HCID 6422三氟乙酸HCID 57699520Tert-butyl 4-(3-fluorophenoxy)piperidine-1-carboxylate

产物 1

HCID 185240024-(3-氟苯氧基)哌啶收率 111.8%

试剂、催化剂与溶剂 1

HCID 6344二氯甲烷溶剂

实验过程

A solution of 1,1-dimethylethyl 4-[(3-fluorophenyl)oxy]-1-piperidinecarboxylate (D11) (16.4 g, 55 mmol) in DCM (200 ml) at 0° C. was treated with TFA (17 ml). The reaction was warmed to room temperature and stirred overnight. The solvent was then removed in vacuo and the residue partitioned between DCM and 2M NaOH solution. The aqueous was further extracted with DCM (×2) and the combined organics concentrated in vacuo. The residue was re-dissolved in DCM and extracted with 2M HCl (×2) which was then basified with 2M NaOH and re-extracted with DCM (×3). The combined organics were concentrated in vacuo to give the title compound (12 g). δH (CDCl3, 250 MHz) 1.66 (2H, m), 2.01 (2H, m), 2.73 (2H, m), 3.14 (2H, m), 4.34 (1H, m), 6.68 (3H, m), 7.19 (1H, m), MS (ES): MH+ 196. This whole was diluted with MeOH and treated with 1M HCl in Et2O to give the hydrochloride salt of the title compound (8.0 g).

后处理

  1. customThe solvent was then removed in vacuo
  2. customthe residue partitioned between DCM and 2M NaOH solution
  3. extractionThe aqueous was further extracted with DCM (×2)
  4. concentrationthe combined organics concentrated in vacuo
  5. dissolutionThe residue was re-dissolved in DCM
  6. extractionextracted with 2M HCl (×2) which
  7. extractionre-extracted with DCM (×3)
  8. concentrationThe combined organics were concentrated in vacuo

来源与证据

ORD记录
ord-a2881ee2bc494afc87a53d881073b817
来源数据集
uspto-grants-2011_09
专利号
US08012981B2

反应笔记

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