4-溴丁腈 → (R)-tert-butyl 3-((R)-(3-chlorophenyl)(3-cyanopropoxy)methyl)piperidine-1-carboxylate

HRID 451908笔记

反应方程式

HRID 451908 反应方程式
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([C@H:10]([OH:24])[C@@H:11]2[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]2)[CH:7]=[CH:8][CH:9]=1.Br[CH2:26][CH2:27][CH2:28][C:29]#[N:30].[NH4+].[Cl-]>CC#N.C(OCC)(=O)C>[Cl:3][C:4]1[CH:5]=[C:6]([C@H:10]([O:24][CH2:26][CH2:27][CH2:28][C:29]#[N:30])[C@@H:11]2[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:18])[CH2:12]2)[CH:7]=[CH:8][CH:9]=1

参与物

7

反应物 4

HCID 214124-溴丁腈HCID 24758氢化钠HCID 25517氯化铵HCID 445550221-Piperidinecarboxylic acid, 3-[(R)-(3-chlorophenyl)hydroxymethyl]-, 1,1-dimethylethyl ester, (3R)-

产物 1

HCID 68714485(R)-tert-butyl 3-((R)-(3-chlorophenyl)(3-cyanopropoxy)methyl)piperidine-1-carboxylate收率 23.5%

试剂、催化剂与溶剂 2

HCID 6342乙腈溶剂2 次HCID 8857乙酸乙酯溶剂

实验过程

To a suspension of NaH (763 mg, 19.1 mmol) and (R)-tert-butyl 3-((R)-(3-chlorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (1.55 g, 4.77 mmol) in CH3CN (20 mL) at 0-5° C. was added dropwise a solution of 4-bromobutyronitrile (3.17 g, 21.5 mmol) in CH3CN (5 mL), the reaction mixture was stirred for overnight at rt. The reaction mixture was poured into saturated aqueous NH4Cl, ethyl acetate (50 mL) was added. The organic layer was washed with water (3×20 mL) and brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by preparative HPLC to afford (R)-tert-butyl 3-((R)-(3-chlorophenyl)(3-cyanopropoxy)methyl)piperidine-1-carboxylate (0.44 g, 21% yield). 1H NMR (CD3OD, 400 MHz) δ 7.38-7.28 (m, 3H), 7.22 (m, 1H), 4.22 (m, 1H), 4.02 (d, 1H), 3.86 (d, 1H), 3.34 (m, 2H), 2.77 (q, 2H), 2.56 (t, 2H), 1.62 (m, 1H), 1.59 (m, 1H), 1.43 (s, 9H), 1.35-1.25 (m, 3H), 1.12 (d, 1H).

后处理

  1. additionwas added
  2. washThe organic layer was washed with water (3×20 mL) and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative HPLC

来源与证据

ORD记录
ord-695bdd89cf9542e49e108f5ae34bf9c9
来源数据集
uspto-grants-2013_07
专利号
US08487108B2

反应笔记

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