Acetic Acid → HCID 86732821, compound

HRID 525952Notes

Reaction equation

HRID 525952 reaction equation
[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][CH:9]=[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:33])[C:5]([CH:34]=O)=[CH:4]1)[CH3:2].[NH:36]1[CH2:40][CH2:39][CH2:38][CH2:37]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CC(O)=O>ClCCl>[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][CH:9]=[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:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[C:6](=[O:33])[C:5]([CH2:34][N:36]2[CH2:40][CH2:39][CH2:38][CH2:37]2)=[CH:4]1)[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 31268PyrrolidineHCID 5049666Sodium triacetoxyborohydrideHCID 86732820HCID 86732820, compound

Product 1

HCID 86732821HCID 86732821, compoundYield 41.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 1-ethyl-7,8-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carbaldehyde (10 g, 21.12 mmol) in Dichloromethane (DCM) (150 mL) was added pyrrolidine (2.61 mL, 31.7 mmol), sodium triacetoxyborohydride (8.95 g, 42.2 mmol) and AcOH (0.060 mL, 1.056 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 layer 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 120 g 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-7,8-bis((4-methoxybenzyl)oxy)-3-(pyrrolidin-1-ylmethyl)quinolin-4(1H)-one (4.6 g, 8.70 mmol, 41.2% yield) as a pale yellow solid. LCMS: (M+H)+: 529.4.

Workup

  1. customcompletion of the reaction
  2. extractionThe mixture was extracted with DCM
  3. washwashed with brine
  4. dry with materialThe organic layer 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-e65c52dd64354b6ca2ccc21d333394b3
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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