4-Methylmorpholine → Isopropyl 2-(3-(3-hexylquinoline-8-carboxamido)phenoxy)acetate

HRID 472792Notes

Reaction equation

HRID 472792 reaction equation
[CH2:1]([C:7]1[CH:8]=[N:9][C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][C:11]=2[C:17]([OH:19])=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[NH2:20][C:21]1[CH:22]=[C:23]([CH:32]=[CH:33][CH:34]=1)[O:24][CH2:25][C:26]([O:28][CH:29]([CH3:31])[CH3:30])=[O:27].CN1CCOCC1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C=O)C>[CH2:1]([C:7]1[CH:8]=[N:9][C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][C:11]=2[C:17]([NH:20][C:21]1[CH:22]=[C:23]([CH:32]=[CH:33][CH:34]=1)[O:24][CH2:25][C:26]([O:28][CH:29]([CH3:30])[CH3:31])=[O:27])=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10608474Isopropyl 2-(3-aminophenoxy)acetateHCID 666608943-Hexylquinoline-8-carboxylic acid

Product 1

HCID 66660805Isopropyl 2-(3-(3-hexylquinoline-8-carboxamido)phenoxy)acetateYield 87.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-hexylquinoline-8-carboxylic acid (170 mg, 0.66 mmol), isopropyl 2-(3-aminophenoxy)acetate (207 mg, 0.99 mmol) and N-methylmorpholine (0.18 mL, 1.65 mmol) in DMF (2.0 mL) was added O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (380 mg, 1.0 mmol) and the solution was stirred at room temperature for 16 h. The DMF was removed in vacuo and the residue was partitioned between EtOAc and water. The organic phase was washed with saturated aqueous NaHCO3 (2×) then dried (MgSO4), filtered and concentrated in vacuo. The resulting residue was purified on 12 g silica gel eluting (17:3 hexanes/EtOAc) to afford 259 mg (87%) of isopropyl 2-(3-(3-hexylquinoline-8-carboxamido)phenoxy)acetate.

Workup

  1. customThe DMF was removed in vacuo
  2. customthe residue was partitioned between EtOAc and water
  3. washThe organic phase was washed with saturated aqueous NaHCO3 (2×)
  4. dry with materialthen dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified on 12 g silica gel eluting (17:3 hexanes/EtOAc)

Sources & evidence

ORD record
ord-ba8da0b802cf4abab4f1e60353c7eef4
Source dataset
uspto-grants-2014_01
Patent number
US08633220B2

Reaction notes

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