Pyrrolidine → 1-ethyl-6-fluoro-7,8-bis((4-methoxybenzyl)oxy)-3-(pyrrolidin-1-ylmethyl)quinolin-4(1H)-one

HRID 525945Notes

Reaction equation

HRID 525945 reaction equation
[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:33])=[C:10]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=3)[C:11]=2[O:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[C:6](=[O:34])[C:5]([CH:35]=O)=[CH:4]1)[CH3:2].[NH:37]1[CH2:41][CH2:40][CH2:39][CH2:38]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.CC(O)=O>[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:33])=[C:10]([O:23][CH2:24][C:25]3[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=3)[C:11]=2[O:13][CH2:14][C:15]2[CH:16]=[CH:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=2)[C:6](=[O:34])[C:5]([CH2:35][N:37]2[CH2:41][CH2:40][CH2:39][CH2:38]2)=[CH:4]1)[CH3:2]

Participants

6

Reactant 3

HCID 31268PyrrolidineHCID 5049666Sodium triacetoxyborohydrideHCID 867328131-Ethyl-6-fluoro-7,8-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carbaldehyde

Product 1

HCID 867328141-ethyl-6-fluoro-7,8-bis((4-methoxybenzyl)oxy)-3-(pyrrolidin-1-ylmethyl)quinolin-4(1H)-oneYield 58.8%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 111,2-DichloroethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 1-ethyl-6-fluoro-7,8-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carbaldehyde (15 g, 30.5 mmol) in 1,2-Dichloroethane (DCE) (100 mL) was added pyrrolidine (3.78 mL, 45.8 mmol), sodium triacetoxyborohydride (12.94 g, 61.0 mmol) and AcOH (0.087 mL, 1.526 mmol). The reaction mixture was stirred at 25° C. for 3 h. LCMS showed completion of the reaction. The mixture was extracted with DCM and washed with brine. The organic solution was dried over sodium sulfate and evaporated in vacuo. The crude material was purified by normal phase automatic silica column chromatography (Combiflash RF), using a 40 g golden column and eluting with MeOH/DCM (0-20%). The product was further purified with reverse phase automatic silica column chromatography (Combiflash RF), using a 150 g golden column and eluting with acetonitrile/water (0-60%) to afford 1-ethyl-6-fluoro-7,8-bis((4-methoxybenzyl)oxy)-3-(pyrrolidin-1-ylmethyl)quinolin-4(1H)-one (9.8 g, 17.93 mmol, 58.7% yield) as a yellow solid. LCMS: (M+H)+: 547.4.

Workup

  1. customcompletion of the reaction
  2. extractionThe mixture was extracted with DCM
  3. washwashed with brine
  4. dry with materialThe organic solution was dried over sodium sulfate
  5. customevaporated in vacuo
  6. customThe crude material was purified by normal phase automatic silica column chromatography (Combiflash RF)
  7. washeluting with MeOH/DCM (0-20%)
  8. customThe product was further purified with reverse phase automatic silica column chromatography (Combiflash RF)
  9. washeluting with acetonitrile/water (0-60%)

Sources & evidence

ORD record
ord-1f3116bd575b4d428c3a55a1cdd020b7
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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