Dimethylformamide → HCID 68184855, compound

HRID 2041692Notes

Reaction equation

HRID 2041692 reaction equation
[N:1]([CH2:4][CH2:5][OH:6])=[N+:2]=[N-:3].CN(C)C=O.CC([N:16]([C@H:20]1[C:29]2[C:24](=[CH:25][CH:26]=[C:27]([C:30]#[CH:31])[CH:28]=2)[N:23]([C:32](=[O:34])[CH3:33])[C@@H:22]([CH3:35])[CH2:21]1)[C:17](=[O:19])[O-:18])(C)C>[Cu]I.CO>[C:32]([N:23]1[C:24]2[C:29](=[CH:28][C:27]([C:30]3[N:3]=[N:2][N:1]([CH2:4][CH2:5][OH:6])[CH:31]=3)=[CH:26][CH:25]=2)[C@H:20]([NH:16][C:17](=[O:19])[O:18][C:27]([CH3:30])([CH3:28])[CH3:26])[CH2:21][C@@H:22]1[CH3:35])(=[O:34])[CH3:33]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 1231182-AzidoethanolHCID 86669437HCID 86669437, compound

Product 1

HCID 68184855HCID 68184855, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

A flask was charged with 2-azidoethanol (318 mg, 3.65 mmol) and copper(I) iodide (17.40 mg, 0.091 mmol) then filled with N,N-dimethylformamide (DMF) (13 mL) and methanol (1.5 mL). This mixture was treated with 1,1-dimethylethyl[(2S,4R)-1-acetyl-6-ethynyl-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation see Intermediate 48) (600 mg, 1.827 mmol) and the resulting mixture was stirred at 100° C. for 2 h under microwave irradiation then cooled to room temperature and partitioned between EtOAc and water. The layers were separated and the aqueous phase was extracted three times with EtOAc. The combined organic layers were washed twice with brine, and then dried over MgSO4 and concentrated in vacuovacuo. Purification of the residue by flash chromatography on silica gel (gradient:0 to 5% MeOH in DCM) gave 1,1-dimethylethyl {(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 (659 mg, 1.523 mmol, 83% yield).

Workup

  1. temperaturethen cooled to room temperature
  2. custompartitioned between EtOAc and water
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted three times with EtOAc
  5. washThe combined organic layers were washed twice with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuovacuo
  8. customPurification of the residue by flash chromatography on silica gel (gradient:0 to 5% MeOH in DCM)

Sources & evidence

ORD record
ord-da395777ef0240a0b16aa881b8ece17b
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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