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

HRID 577439Notes

Reaction equation

HRID 577439 reaction equation
[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

Participants

8

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 517166Dichlorocobalt hexahydrateCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

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].

Workup

  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)

Sources & evidence

ORD record
ord-caf627713eac4eb18d705ffb525a203a
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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