tert-Butanol → Tert-butyl [1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinolin-5-yl]carbamate

HRID 577517Notes

Reaction equation

HRID 577517 reaction equation
[O:1]=[C:2]1[C:11]2[CH:10]=[C:9]([O:12][CH:13]([CH3:15])[CH3:14])[CH:8]=[C:7](C(O)=O)[C:6]=2[CH2:5][CH2:4][NH:3]1.C1N=CN([C:24]([N:26]2C=NC=C2)=[O:25])C=1.[C:31]([OH:35])([CH3:34])([CH3:33])[CH3:32]>O1CCOCC1>[O:1]=[C:2]1[C:11]2[C:6](=[C:7]([NH:26][C:24](=[O:25])[O:35][C:31]([CH3:34])([CH3:33])[CH3:32])[CH:8]=[C:9]([O:12][CH:13]([CH3:14])[CH3:15])[CH:10]=2)[CH2:5][CH2:4][NH:3]1

Participants

5

Reactant 3

HCID 6386tert-ButanolHCID 682631,1'-CarbonyldiimidazoleHCID 867237431-Oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acid

Product 1

HCID 86723744Tert-butyl [1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinolin-5-yl]carbamateYield 42%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a suspension of 1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acid (77a, 1.76 g, 7.06 mmol) in anhydrous dioxane (100 mL) was added CDI (1.43 g, 8.83 mmol). The resulting mixture was stirred at room temperature for 30 minutes, then stirred at 100° C. for 30 minutes. After cooling down to room temperature, TMSA (1.50 mL, 10.8 mmol) was added. After stirring the reaction mixture for 2 hours, t-butanol (25.0 mL) was added. The resulting mixture was stirred at 100° C. overnight. After cooling to room temperature and concentrating under vacuum, the resulting residue was purified by column chromatography (0-100% EtOAc/heptanes) to give tert-butyl [1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinolin-5-yl]carbamate (77b, 958 mg, 42%) as a solid.

Workup

  1. stirringstirred at 100° C. for 30 minutes
  2. temperatureAfter cooling down to room temperature
  3. additionTMSA (1.50 mL, 10.8 mmol) was added
  4. stirringAfter stirring the reaction mixture for 2 hours
  5. stirringThe resulting mixture was stirred at 100° C. overnight
  6. temperatureAfter cooling to room temperature
  7. concentrationconcentrating under vacuum
  8. customthe resulting residue was purified by column chromatography (0-100% EtOAc/heptanes)

Sources & evidence

ORD record
ord-5ba9e2ece35e4d469895539e52347839
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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