Water → Methyl 1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinoline-5-carboxylate

HRID 577439ノート

反応式

HRID 577439 の反応式
[C:1]([CH2:3][C:4]1[C:9]([C:10]([O:12][CH3:13])=[O:11])=[CH:8][C:7]([O:14][CH:15]([CH3:17])[CH3:16])=[CH:6][C:5]=1[C:18]([O:20]C)=O)#[N:2].[BH4-].[Na+].[NH4+].[Cl-].O>CO.O.O.O.O.O.O.[Co](Cl)Cl.CCOC(C)=O>[O:20]=[C:18]1[C:5]2[CH:6]=[C:7]([O:14][CH:15]([CH3:17])[CH3:16])[CH:8]=[C:9]([C:10]([O:12][CH3:13])=[O:11])[C:4]=2[CH2:3][CH2:1][NH:2]1

参加物

8

反応物 4

HCID 962WaterHCID 25517Ammonium ChlorideHCID 4311764Sodium borohydrideHCID 86723678Dimethyl 2-(cyanomethyl)-5-(propan-2-yloxy)benzene-1,3-dicarboxylate

生成物 1

HCID 86723679Methyl 1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinoline-5-carboxylate収率 69%

試薬・触媒・溶媒 3

HCID 517166Dichlorocobalt hexahydrate触媒HCID 887Methanol溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

Dimethyl 2-(cyanomethyl)-5-(propan-2-yloxy)benzene-1,3-dicarboxylate (Cpd D, 1.04 g, 3.57 mmol) and cobalt (II) chloride hexahydrate (2.56 g, 10.7 mmol) were dissolved in MeOH (60 mL) and cooled in an ice bath. NaBH4 (853 mg, 21.4 mmol) was added portionwise and the reaction mixture was stirred at 0° C. for 0.5 hours. To the reaction mixture was added NH4Cl (sat., aq., 25 mL), H2O (25 mL), and EtOAc (50 mL). The solution was allowed to sit at room temperature overnight. The residual solids were filtered and the aqueous layer was extracted with EtOAc (3×50 mL). The combined organic layers were washed with brine (1×50 mL), dried over sodium sulfate, concentrated under vacuum, and purified by column chromatography (0-60%, EtOAc/heptanes) to afford methyl 1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinoline-5-carboxylate (Cpd E, 644 mg, 69% yield) as a white solid. 1H NMR (400 MHz, chloroform-d) δ 1.35 (s, 3H) 1.36 (s, 3H) 3.35 (t, J=6.57 Hz, 2H) 3.52 (td, J=6.57, 3.03 Hz, 2H) 3.91 (s, 3H) 4.61-4.72 (m, 1H) 5.91 (br. s., 1H) 7.62 (d, J=3.03 Hz, 1H) 7.83 (d, J=3.03 Hz, 1H); MS 264.1 [M+H].

後処理

  1. temperaturecooled in an ice bath
  2. waitto sit at room temperature overnight
  3. filtrationThe residual solids were filtered
  4. extractionthe aqueous layer was extracted with EtOAc (3×50 mL)
  5. washThe combined organic layers were washed with brine (1×50 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under vacuum
  8. custompurified by column chromatography (0-60%, EtOAc/heptanes)

出典と根拠

ORDレコード
ord-caf627713eac4eb18d705ffb525a203a
出典データセット
uspto-grants-2015_05
特許番号
US09040515B2

反応ノート

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