Methyl iodide → tert-butyl 5,6-dimethoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 717371Notes

Reaction equation

HRID 717371 reaction equation
[OH:1][C:2]1[C:11]([O:12][CH3:13])=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:7]2.[H-].[Na+].CI.[CH:25](OC(C)(C)C)=O>CN(C)C=O.O.C(OCC)(=O)C>[CH3:25][O:1][C:2]1[C:11]([O:12][CH3:13])=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:7]2

Participants

8

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 61207tert-Butyl FormateHCID 90411670tert-butyl 5-hydroxy-6-methoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 90410651tert-butyl 5,6-dimethoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Into a 50-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of tert-butyl 5-hydroxy-6-methoxy-1,2,3,4-tetrahydroisoquinoline-2-carboxylate (100 mg, 0.36 mmol, 1.00 equiv) in N,N-dimethylformamide (10 mL) and sodium hydride (12.9 mg, 1.50 equiv). This was followed by the addition of CH3I (254.2 mg, 5.00 equiv). The resulting solution was stirred overnight at room temperature. The resulting solution was diluted with 100 mL of water. The resulting solution was extracted with 3×30 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. This resulted in 85 mg (81%) of tert-butyl 5,6-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-carboxylate as a light yellow solid. MS (ESI) m/z 194 ([M+H-t-Boc]+); Rf 0.28 (starting material) and 0.43 (product) in ethyl acetate:petroleum ether=1:3.

Workup

  1. customInto a 50-mL 3-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. extractionThe resulting solution was extracted with 3×30 mL of ethyl acetate
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThis resulted in 85 mg (81%) of tert-butyl 5,6-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-carboxylate as a light yellow solid

Sources & evidence

ORD record
ord-4b7efff26d994963b7e2ede42a11bc2c
Source dataset
uspto-grants-2015_11
Patent number
US09193707B2

Reaction notes

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