三乙烯二胺 → Dimethyl 1,4,6,7-tetrahydropyrano[4,3-b]pyrrole-2,3-dicarboxylate

HRID 1473264

反应方程式

HRID 1473264 反应方程式
[O:1]1[CH2:6][CH2:5][C:4](=[N:7]O)[CH2:3][CH2:2]1.[CH3:9][O:10][C:11]([C:13]#[C:14][C:15]([O:17][CH3:18])=[O:16])=[O:12].C1N2CCN(CC2)C1>C1(C)C=CC=CC=1>[NH:7]1[C:13]([C:11]([O:10][CH3:9])=[O:12])=[C:14]([C:15]([O:17][CH3:18])=[O:16])[C:3]2[CH2:2][O:1][CH2:6][CH2:5][C:4]1=2

参与物

5

反应物 3

HCID 9237三乙烯二胺HCID 12980丁炔二酸二甲酯HCID 12298558二氢-2H-吡喃-4(3H)-酮肟

产物 1

HCID 117700715Dimethyl 1,4,6,7-tetrahydropyrano[4,3-b]pyrrole-2,3-dicarboxylate收率 22%

试剂、催化剂与溶剂 1

HCID 1140甲苯溶剂

反应条件

温度
165 °C

实验过程

A suspension of dihydro-2H-pyran-4(3H)-one oxime (7 g, 60.8 mmol), dimethylacetylene dicarboxylate (9.72 ml, 79 mmol), and DABCO (2.046 g, 18.24 mmol) in Toluene (27.5 ml) were heated to 165° C. After 2 h, the reaction mixture was cooled to ambient temperature, concentrated in vacuo and purified by ISCO (0-100% EtOAc-hexanes) to afford dimethyl 1,4,6,7-tetrahydropyrano[4,3-b]pyrrole-2,3-dicarboxylate (3.2 g, 13.38 mmol, 22.00% yield) as a yellow solid. The residue was dissolved in DMF (30 mL), and treated with Cs2CO3 (5.29 g, 16.23 mmol) and 4-fluorobenzyl bromide (2.023 ml, 16.23 mmol). After 2 h, the reaction mixture was partitioned between EtOAc and sat. aq. NH4Cl. The organic layer was washed with water, brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by ISCO (0-50% EtOAc-hexanes; 120 g column) to afford dimethyl 1-(4-fluorobenzyl)-1,4,6,7-tetrahydropyrano[4,3-b]pyrrole-2,3-dicarboxylate (3.92 g, 11.29 mmol, 18.56% yield) as a yellow oil. LCMS (m/z) ES+=348 (M+1).

后处理

  1. temperaturethe reaction mixture was cooled to ambient temperature
  2. concentrationconcentrated in vacuo
  3. custompurified by ISCO (0-100% EtOAc-hexanes)

来源与证据

ORD记录
ord-661e15bc5dc7482c8a90bd0547efda7b
来源数据集
uspto-grants-2015_04
专利号
US09012642B2

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