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

HRID 445456Notes

Reaction equation

HRID 445456 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.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C=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

6

Reactant 4

HCID 712FormaldehydeHCID 6422Trifluoroacetic acidHCID 5049666Sodium triacetoxyborohydrideHCID 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 mmol) 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. waitThe stirring was continued for 12 h
  3. customThe reaction was quenched with sat. aqueous NaHCO3
  4. addition15% NaOH was added until PH=14
  5. extractionThe product was extracted with EtOAc
  6. customRemoval of the solvent in vacuo

Sources & evidence

ORD record
ord-5834e75939f942c3aa714b6cead38027
Source dataset
uspto-grants-2013_07
Patent number
US08476298B2

Reaction notes

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