Triethylamine → HCID 45380175, compound

HRID 1511568Notes

Reaction equation

HRID 1511568 reaction equation
[C:1]([N:8]1[CH:12]=[CH:11]N=[CH:9]1)(N1C=CN=C1)=[O:2].[CH3:13][O:14][C:15](=[O:29])[C@@H:16]1[CH2:20][C@@H:19]([OH:21])[CH2:18][N:17]1[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23].[OH:30][C:31]1[CH:32]=[CH:33][CH:34]=[C:35]2[C:40]=1CNCC2.CCN(CC)CC.[NH4+].[Cl-]>CN(C=O)C>[OH:30][C:31]1[CH:40]=[CH:35][CH:34]=[C:33]2[C:32]=1[CH2:9][N:8]([C:1]([O:21][C@H:19]1[CH2:18][N:17]([C:22]([O:24][C:25]([CH3:26])([CH3:28])[CH3:27])=[O:23])[C@H:16]([C:15]([O:14][CH3:13])=[O:29])[CH2:20]1)=[O:2])[CH2:12][CH2:11]2

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 682631,1'-CarbonyldiimidazoleHCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl esterHCID 136352141,2,3,4-Tetrahydroisoquinolin-8-ol

Product 1

HCID 45380175HCID 45380175, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

Carbonyldiimidazole (0.176 g, 1.086 mmol) was added to a stirred, room temperature solution of DMF (5 mL) and N-Boc-trans-4-hydroxy-L-proline methyl ester (0.21 g, 0.87 mmol) and the mixture was stirred 45 min. 8-Hydroxy-1,2,3,4-tetrahydroisoquinoline (0.20 g, 0.87 mmol) and Et3N (0.18 g, 1.74 mmol) were added and the resulting solution was heated at 50° C. for 2 h. The reaction mixture was poured into aqueous saturated NH4Cl and extracted with EtOAc, dried over Na2SO4 and concentrated to an oil. The residue was purified by column chromatography on silica gel (gradient elution, 10 to 80% EtOAc in hexanes) to give 1-tert-butyl 2-methyl (2S,4R)-4-{[(8-hydroxy-3,4-dihydroisoquinolin-2(1H)-yl)carbonyl]oxy}pyrrolidine-1,2-dicarboxylate (0.25 g, 0.60 mmol, 69% yield) as a colorless foam after evaporation of solvent. LRMS (ESI) m/z 321.3 [((M-Boc)+H)+; calcd for C16H21N2O5: 321.4].

Workup

  1. extractionextracted with EtOAc
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated to an oil
  4. customThe residue was purified by column chromatography on silica gel (gradient elution, 10 to 80% EtOAc in hexanes)

Sources & evidence

ORD record
ord-a47accc833944299b8d19d75e6466d0d
Source dataset
uspto-grants-2012_07
Patent number
US08216999B2

Reaction notes

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