2-Azidoethanol → 1-methylethyl {(2S,4R)-1-acetyl-6-[1-(2-hydroxyethyl)-1H-1,2,3-triazol-4-yl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl}carbamate

HRID 2366937Notes

Reaction equation

HRID 2366937 reaction equation
[CH3:1][CH:2]([O:4][C:5](=[O:23])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]#[CH:18])[CH:15]=2)[N:10]([C:19](=[O:21])[CH3:20])[C@@H:9]([CH3:22])[CH2:8]1)[CH3:3].[N:24]([CH2:27][CH2:28][OH:29])=[N+:25]=[N-:26]>CN(C)C=O.CO.[Cu]I>[C:19]([N:10]1[C:11]2[C:16](=[CH:15][C:14]([C:17]3[N:26]=[N:25][N:24]([CH2:27][CH2:28][OH:29])[CH:18]=3)=[CH:13][CH:12]=2)[C@H:7]([NH:6][C:5](=[O:23])[O:4][CH:2]([CH3:1])[CH3:3])[CH2:8][C@@H:9]1[CH3:22])(=[O:21])[CH3:20]

Participants

6

Reactant 2

HCID 1231182-AzidoethanolHCID 86669236HCID 86669236, compound

Product 1

HCID 529354541-methylethyl {(2S,4R)-1-acetyl-6-[1-(2-hydroxyethyl)-1H-1,2,3-triazol-4-yl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl}carbamateYield 62%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 1-methylethyl[(2S,4R)-1-acetyl-6-ethynyl-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation, see Intermediate 58) (100 mg, 0.318 mmol) in a mixture of N,N-dimethylformamide (DMF) (1.8 mL) and methanol (0.200 mL) were successively added 2-azidoethanol (55.4 mg, 0.636 mmol) and copper(I) iodide (3.03 mg, 0.016 mmol). The resulting mixture was stirred at 100° C. under microwave irradiation for 2 h then cooled to room temperature. The reaction mixture was partitioned between EtOAc and brine and the layers were separated. The aqueous phase was extracted with EtOAc (3×) and the combined organic layers were washed with brine, dried over a Na2SO4 cartridge and concentrated in vacuo. Purification of the residue on SP4 using a 10 G silica cartridge (gradient: 2 to 10% MeOH in DCM) gave 1-methylethyl {(2S,4R)-1-acetyl-6-[1-(2-hydroxyethyl)-1H-1,2,3-triazol-4-yl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl}carbamate (83 mg, 0.198 mmol, 62%) as an off white solid.

Workup

  1. temperaturethen cooled to room temperature
  2. customThe reaction mixture was partitioned between EtOAc and brine
  3. customthe layers were separated
  4. extractionThe aqueous phase was extracted with EtOAc (3×)
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over a Na2SO4 cartridge
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue on SP4

Sources & evidence

ORD record
ord-2f35e861ce644e2aaececd6bfc4dce47
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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