Trifluoroacetic acid → 4-(2-Fluoro-4-nitrophenoxy)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinoline

HRID 562978Notes

Reaction equation

HRID 562978 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][O:15][C:16]2[CH:25]=[C:24]3[C:19]([C:20]([O:26][C:27]4[CH:32]=[CH:31][C:30]([N+:33]([O-:35])=[O:34])=[CH:29][C:28]=4[F:36])=[CH:21][CH:22]=[N:23]3)=[CH:18][C:17]=2[O:37][CH3:38])[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:36][C:28]1[CH:29]=[C:30]([N+:33]([O-:35])=[O:34])[CH:31]=[CH:32][C:27]=1[O:26][C:20]1[C:19]2[C:24](=[CH:25][C:16]([O:15][CH2:14][CH:11]3[CH2:12][CH2:13][N:8]([CH3:6])[CH2:9][CH2:10]3)=[C:17]([O:37][CH3:38])[CH:18]=2)[N:23]=[CH:22][CH:21]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59342475tert-Butyl 4-(((4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinolin-7-yl)oxy)methyl)piperidine-1-carboxylate

Product 1

HCID 596475664-(2-Fluoro-4-nitrophenoxy)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinolineYield 93.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-[4-(2-fluoro-4-nitro-phenoxy)-6-methoxy-quinolin-7-yloxymethyl]-piperidine-1-carboxylic acid tert-butyl ester (305 mg, 0.58 mmol) in CH2Cl2 (1 mL) was added 0.4 mL of TFA. The reaction mixture was stirred for 1.5 h and the solvents were removed under reduced pressure. The crude product was treated with NaBH(OAc)3 (381 mg, 1.80 μmmol) and formaldehyde (0.5 mL, 37% in H2O). The stirring was continued for 12 h. The reaction was quenched with sat. aqueous NaHCO3. 15% NaOH was added until PH=14. The product was extracted with EtOAc. Removal of the solvent in vacuo gave the crude product, 4-(2-fluoro-4-nitro-phenoxy)-6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinoline, (240 mg, 93%), which was used directly in the next reaction.

Workup

  1. customthe solvents were removed under reduced pressure
  2. additionThe crude product was treated with NaBH(OAc)3 (381 mg, 1.80 μmmol) and formaldehyde (0.5 mL, 37% in H2O)
  3. waitThe stirring was continued for 12 h
  4. customThe reaction was quenched with sat. aqueous NaHCO3
  5. addition15% NaOH was added until PH=14
  6. extractionThe product was extracted with EtOAc
  7. customRemoval of the solvent in vacuo

Sources & evidence

ORD record
ord-13e4d16782ee497787d7371ec1a8be7b
Source dataset
uspto-grants-2011_11
Patent number
US08067436B2

Reaction notes

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